Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
OPTOACOUSTIC COMPONENT UTILIZATION TRACKING
[0001] This application claims priority to U.S. Patent Application Serial
No. 13/842,538
filed March 15, 2013. This application is a continuation-in-part of U.S.
Patent Application
No. 13/793,808 filed March 11, 2013, entitled "Statistical Mapping In An
Optoacoustic Imaging
System ," which is a continuation-in-part of U.S. Patent Application No.
13/507,217 filed June
13, 2012 entitled "System and Method for Acquiring Optoacoustic Data and
Producing
Parametric Maps Thereof" This application is also a continuation-in-part of
U.S. Patent
Application No. 13/507,223, filed June 13, 2012, entitled "System and Method
for Storing Data
Associated With the Operation of a Dual Modality Optoacoustic / Ultrasound
System" and U.S.
Patent Application No. 13/341,950, filed December 31, 2011, entitled "System
and Method for
Adjusting the Light Output of an Optoacoustic Imaging System" and U.S. Patent
Application No.
13/287,759 entitled "Handheld Optoacoustic Probe" filed November 2, 2011. This
application is
also a continuation-in-part of U.S. Patent Application No. 12/746,905 filed
January 22, 2013,
entitled "Probe With Optoacoustic Isolator." The entire disclosures of those
applications,
including the CD-ROM Appendix to U.S. Patent Application No. 13/507,217, are
incorporated
herein by reference.
[0002] This application includes material which is subject to copyright
protection. The
copyright owner has no objection to the facsimile reproduction by anyone of
the patent
disclosure, as it appears in the Patent and Trademark Office files or records,
but otherwise
reserves all copyright rights whatsoever.
FIELD
[0003] The present invention relates in general to the field of medical
imaging, and in
particular to system relating to optoacoustic imaging.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] The foregoing and other objects, features, and advantages of the
invention will be
apparent from the following more particular description of preferred
embodiments as illustrated
in the accompanying drawings, in which reference characters refer to the same
parts throughout
the various views. The drawings are not necessarily to scale, emphasis instead
being placed upon
illustrating principles of the invention.
- 1 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[0005] Figure 1 shows a schematic block diagram illustrating an
embodiment of a
combined optoacoustic and ultrasound system that may be used as a platform for
the methods
and devices disclosed herein.
[0006] Figure 2 shows a flow for an illustrative embodiment of a method
of providing
output images resulting from optoacoustic data, and from optoacoustic data
combined with
ultrasound data.
[0007] Figure 3 shows a flow for an illustrative embodiment of a method
for
preprocessing sinograms to remove unwanted information.
[0008] Figure 4 shows a flow for an illustrative embodiment of a method
for image
reconstruction.
[0009] Figure 5 shows a flow for an illustrative embodiment of a method
of post-
processing to produce an envelope image.
[0010] Figure 6 shows a flow for an illustrative embodiment of a method
of performing
fluence compensation.
[0011] Figure 7 shows a flow for an illustrative embodiment of a method
of creating
color parametric maps from the envelope image information.
[0012] Figure 8 shows a flow for an illustrative embodiment of a method
of motion and
tracking processing.
[0013] Figure 9 shows a flow for an illustrative embodiment of a method
of producing
grayscale parametric maps from envelope image information.
[0014] Figures 10-12 show an illustrative four-image displays with
parameter input and
display.
[0015] Figures 13-15 show illustrative six-image displays.
[0016] Figure 16 shows a schematic orthogonal view of an embodiment of a
probe that
may be used in connection with the methods and other devices disclosed herein.
[0017] Figure 17 shows an exploded view of an embodiment of the probe
shown in
Figure 16.
[0018] Figure 18 shows a cutaway view taken along the centerline of the
wider side of
the probe shown in Figure 16.
[0019] Figure 19A is a side view not-to scale diagrammatic two
dimensional
representation of light exiting an optical fiber.
- 2 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[0020] Figure 19B shows an end view of a light pattern that may result on
a surface from
placement of optical fibers directly on to that surface.
[0021] Figure 20A shows an end view of a desirable light pattern for use
in connection
with the optoacoustic techniques discussed herein.
[0022] Figure 20B shows a side view diagrammatic representation of an
effect of a
ground glass beam expander on the light emitting from a fiber shown in Figure
19A.
[0023] Figure 20C shows a side view diagrammatic representation of an
effect of a
concave lens beam expander on the light emitting from a fiber shown in Figure
19A.
[0024] Figure 21 is a representation of a phantom with a variety of
targets therein that
may be used in connection with calibration and testing of an optoacoustic
device.
[0025] Figure 22 is a representation of an active phantom that may be
used in connection
with calibration and testing of an optoacoustic device.
[0026] Figure 23 is a representation of another phantom with a variety of
targets therein
that may be used in connection with calibration and testing of an optoacoustic
device.
[0027] Figures 24A-24C show schematic orthogonal views of alternative
embodiments of
a probe that may be used in connection with the methods and other devices
disclosed herein.
[0028] Figures 25A-25C show a representation of several examples of
various
organizations of two dimensional arrays of transducer elements.
[0029] Figure 26 is an illustrative example of a two-armed forceps-like
probe having
transducer arrays on its arms which can be physically positioned using finger
grips.
[0030] Figure 27 is an illustrative example of a two-armed forceps-like
probe having a
transducer array on one arm and a light source on the other for use in forward
transmission mode.
[0031] Figure 28 is a schematic block diagram illustrating hardware
components of the
system.
[0032] Figure 29 is a block diagram illustrating the illumination
subsystem and control
interfaces of the system in accordance with an embodiment thereof.
[0033] Figure 30 is a pulse diagram illustrating a radiation restriction
in the system.
[0034] Figure 31 is a schematic block diagram of one embodiment of a foot
switch
closure.
[0035] Figure 32 shows an embodiment of a combined optoacoustic and
ultrasound
system with a probe (including a connected light path and connected combined
electrical path
and control lines).
- 3 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[0036] Figure 33 shows an embodiment of a foot switch for use with a
combined
optoacoustic and ultrasound system.
[0037] Figure 34 shows a front view of a probe including a light path and
light path
connector, and a combined electrical path and control lines with a multi-pin
connector therefor,
resting in an embodiment of a probe holder.
[0038] Figure 35 shows a reverse view of a probe including a light path
and light path
connector, and a combined electrical path and control lines with a multi-pin
connector therefor,
resting in an embodiment of a probe holder.
[0039] Figure 36 shows an embodiment of a novel hand-operated fiber optic
connector.
[0040] Figure 37 shows a sheathed fiber optic bundle with one end of the
fibers
surrounded by a stepped ferrule as may be used in a novel hand-operated fiber
optic connector.
[0041] Figure 38 shows a collared stepped ferrule as may be used in a
novel hand-
operated fiber optic connector.
[0042] Figure 39 is a schematic block diagram illustrating an embodiment
of a light
subsystem for use in a combined optoacoustic and ultrasound system.
[0043] Figure 40 shows an embodiment of a power meter for use in
calibration of the
optoacoustic system.
[0044] Figure 41 is a schematic diagram illustrating an embodiment of a
hardware testing
system for use in testing certain portions of the optoacoustic system.
[0045] While the invention is amenable to various modifications and
alternative forms,
specifics thereof have been shown by way of example in the drawings and will
be described in
detail. It should be understood, however, that the intention is not to limit
the invention to the
particular embodiments described. On the contrary, the intention is to cover
all modifications,
equivalents, and alternatives falling within the spirit and scope of the
invention.
DETAILED DESCRIPTION
[0046] The following description and drawings are illustrative and are
not to be construed
as limiting. Numerous specific details are described to provide a thorough
understanding.
However, in certain instances, well-known or conventional details are not
described in order to
avoid obscuring the description. References to one or an embodiment in the
present disclosure
are not necessarily references to the same embodiment; and, such references
mean at least one.
[0047] Reference in this specification to "one embodiment" or "an
embodiment" means
that a particular feature, structure, or characteristic described in
connection with the embodiment
- 4 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
is included in at least one embodiment of the disclosure. The appearances of
the phrase "in one
embodiment" in various places in the specification are not necessarily all
referring to the same
embodiment, nor are separate or alternative embodiments mutually exclusive of
other
embodiments. Moreover, various features are described which may be exhibited
by some
embodiments and not by others. Similarly, various requirements are described
which may be
requirements for some embodiments but not other embodiments.
[0048] The systems and methods are described below with reference to,
among other
things, block diagrams, operational illustrations and algorithms of methods
and devices to
process optoacoustic imaging data. It is understood that each block of the
block diagrams,
operational illustrations and algorithms and combinations of blocks in the
block diagrams,
operational illustrations and algorithms, can be implemented by means of
analog or digital
hardware and computer program instructions.
[0049] These computer program instructions can be provided to a processor
of a general
purpose computer, special purpose computer, ASIC, or other programmable data
processing
apparatus, such that the instructions, which execute via the processor of the
computer or other
programmable data processing apparatus, implements the functions/acts
specified in the block
diagrams, operational block or blocks and or algorithms.
[0050] In some cases frequency domain based algorithms require zero or
symmetric
padding for performance. This padding is not essential to describe the
embodiment of the
algorithm so it is sometimes omitted from the description of the processing
steps. In some cases,
where padded is disclosed in the steps, the algorithm may still be carried out
without the padding.
In some cases padding is essential, however, and cannot be removed without
corrupting the data.
[0051] In some alternate implementations, the functions/acts noted in the
blocks can
occur out of the order noted in the operational illustrations. For example,
two blocks shown in
succession can in fact be executed substantially concurrently or the blocks
can sometimes be
executed in the reverse order, depending upon the functionality/acts involved.
[0052] Reference will now be made in more detail to various embodiments
of the present
invention, examples of which are illustrated in the accompanying drawings and
the Appendix
filed in related U.S. Patent Application No. 13/507,217, filed June 13, 2012.
As will be apparent
to one of skill in the art, the data structures described in the Appendix and
processing steps
described in the Appendix (including in pseudo-code) may be implemented in a
variety of other
ways without departing from the spirit of the disclosure and scope of the
invention herein. The
- 5 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Appendix is intended to provide one manner of implementing the concepts
disclosed herein the
purpose of illustration and to facilitate understanding.
System and Method for Presenting Optoacoustic Data
[0053] Turning to Figure 1, and as described generally below under the
heading
Optoacoustic System and Method is a device 100, including a probe 102
connected via a light
path 132 and an electrical path 108 to a system chassis 101. Within the system
chassis 101 is
housed a light subsystem 129 and a computing subsystem 128. The computing
subsystem 128
includes one or more computing components for, among other things,
optoacoustic control and
analysis. In an embodiment, through the sampling of transducers in the probe
102, the device
100 can obtain data received in response to: stimulation caused by pulsed
light sources 130, 131
(i.e., the optoacoustic return signal); and to stimulation caused by acoustic
output of the
ultrasound transducer elements.
[0054] In an embodiment, to obtain an optoacoustic return signal
corresponding to a
single light event occurring in a volume of tissue, the transducers in the
probe 102 can be
sampled for a period of time after the light event. In an embodiment, the
transducers in the probe
102 can be sampled for a period of time after the light event approximately
equal to the time it
would take sound to travel a desired distance in the tissue. In an embodiment,
the desired
distance may be at least one centimeter. In an embodiment, the desired
distance may be at least
two centimeters. In an embodiment, the period of sampling would correspond to
the amount of
time it would take sound to travel at least one, but not more than 15
centimeters in tissue. In an
embodiment, the period of sampling would correspond to the amount of time it
would take sound
to travel at least five, but not more than 12 centimeters in tissue. In an
embodiment, the desired
distance may be less than one centimeter. The sampling rate should be
sufficient to obtain
sufficient information in the optoacoustic return signal. In an embodiment,
the sampling rate is
above 20 Mhz, in another embodiment, the sampling rate is above about 30 Mhz.
In an
embodiment the sampling is at least 8 bits, and more preferably more than 12
bits. In an
embodiment, sampling is done at 14 bits. In an embodiment, sampling is done at
resolutions
higher than 14 bits.
[0055] In an exemplary embodiment, to obtain the optoacoustic return
signal, 128 or 256
transducers (i.e., channels) in a probe 102 are sampled at 14 bits for
approximately 65
microseconds ( s) at a sampling rate of 31.25 Mhz. The 65 las of sampling at
31.25 Mhz results
in over 2,000 samples. In an embodiment, 2,045 14 bit samples may be stored
for each
- 6 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
transducer or channel. For efficiency, the 14 bit samples can be stored in a
16 bit computer
word. The samples associated with a single light event, along with additional
header information
relating to the light event, can be stored in a frame of about 512 KB
(kilobytes) for 128 channels,
or 1 MB (megabyte) for 256 channels. Thus, in an exemplary embodiment, the
optoacoustic
return signal from a light event, including header information, can be stored
in either 512 KB, or
1 MB. As discussed further below, in an embodiment, the device 100 comprises
at least two
light sources 130, 131 operating at different light wavelengths. In an
embodiment with two light
sources 130, 131 operating at different light wavelengths, the optoacoustic
return signal from one
light event from each of the light sources can be used in the method and
system for presenting the
optoacoustic data. In an embodiment, the device 100 comprises a single light
source that may be
operated at different wavelengths, such as a tunable laser that can change
wavelengths quickly
enough for use as described herein. In an embodiment, the device 100 comprises
at least two
light sources 130, 131, each being capable of tuning to a plurality of
different wavelengths. In an
embodiment, the device 100 comprises one light source 130 operating a one
light wavelength,
and at least one additional light source 131 capable of being tuned to a
plurality of different
wavelengths.
[0056] As used herein, the term sinogram refers to sampled data or
processed sampled
data corresponding to a single light event. The term sinogram is also used at
times to refer to an
image presented by using the original or filtered sampled data as gray scale
or color data,
wherein there is a correspondence between the samples in the data and the
voxels in the image.
In an embodiment using optoacoustic return signals from two different light
events, each
corresponding to a different wavelength of light, the term short sinogram
refers to the sinogram
corresponding to the shorter wavelength of light generating a light event, and
the term long
sinogram refers to the sinogram corresponding to the longer wavelength of
light generating a
light event. Because more than two different wavelengths may be used, the use
of the terms
short and long wavelength are intended to embody the extended context of a
system with an
arbitrary number of wavelengths.
[0057] In an embodiment, as discussed in more detail below, sinograms are
processed to
produce an envelope image. As used herein the term short envelope image refers
to an envelope
image corresponding to the short sinogram, and the term long envelope image
refers to an
envelope image corresponding to the long sinogram. In an embodiment, the short
sinogram and
long sinogram are each processed separately to produce a short envelope image
and a long
- 7 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
envelope image, respectively. The short and long envelope images are then used
together to
generate parametric images. From the parametric images, maps can be created of
oxygenation,
hemoglobin and masked oxygenation. These maps can be co-registered data
representing an
ultrasound image of substantially the same volume, and can thereafter produce
one or more of an
oxygenation image, a hemoglobin image and a masked oxygenation image. In an
embodiment,
the oxygenation image, hemoglobin image and masked oxygenation image reflect
information
about the composition of the volume of tissue. The terms parametric map and
parametric image
are in some instances used interchangeably. The use of the term map generally
relates to the
correspondence between the image and a volume. Parametric maps may be
represented in
numerous ways, including, for example, as a single-channel (i.e., grayscale)
representation, as a
color (i.e., RGB) representation, or as a color with transparency (RGBA)
representation.
Parametric maps may be used to convey qualitative or quantitative information
about one or
more parameters. A parametric map or parametric image may be represented in
computer
memory or presented as a displayed representation, thus, as used herein, the
term "image" or
"map" do not necessarily imply a visual representation.
Storing Sinogram And Other System Data
[0058] In an embodiment, the sinogram, along with other data recorded
relating to the use
of the optoacoustic device, may be recorded in a laser optic movie file or
LOM. The LOM is not,
as the name would suggest, a movie file, but rather, the LOM is a collection
of recorded data that
may be recorded in group of related files, or more preferably, in a single
data file. One
consideration for the format of the LOM is the differing and likely
asynchronous processes that
generate data requiring storage in the LOM. In an embodiment, the LOM can be
used to store a
variety of information concerning the use of the optoacoustic device,
including, without
limitation, the long and short optoacoustic sinograms, ultrasound frames,
configuration data,
annotations made by a user, or at a later time, an audio and/or video
recording made during the
use of the optoacoustic device and information concerning version information
as reported by the
optoacoustic system and its software.
[0059] In an embodiment, the LOM may be structured in blocks of 1024
bytes (1K) each.
Each collection of information (e.g., a sinogram) may comprise a header, and,
where additional
data is required, one or more additional blocks of information associated with
the header. In an
embodiment, the header may include an identifier that is used to identify the
block as a header.
In an embodiment, the header may also include a value for a synchronization
counter to permit
- 8 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
the collection of information to be placed in proper order when the LOM is
used, even if it is
recorded in the LOM out of order, as may be the case with the varied types of
inputs and I/0
systems in a particular implementation. In an embodiment, the header further
comprises a CRC
of itself and any additional data associated with the collection, thus
permitting an integrity check
or validation of the entire collection within the LOM. A data structure for an
exemplary LOM is
provided in the Appendix.
Processing Sinograms
[0060] For a variety of reasons, sinograms may contain unwanted,
inaccurate or
insufficiently scaled data. These maladies of sinogram data may result from
myriad reasons,
including characteristics of the measuring instrument (e.g., the probe) or the
light used,
characteristics of the volume (i.e., the tissue), characteristics of the
interaction between the
volume and the probe or light, external stimuli, or other sources. Regardless
of the source, a
variety of processes can be used to remove unwanted aspects of the sinogram
data.
[0061] In an exemplary embodiment, where the sinogram data is sampled as
an integer,
e.g., as a 14 bit integer, prior to performing the processing steps on the
sinogram, the sinogram
data may be converted from integer form to a floating point number. Conversion
from integer to
floating point is performed to increase accuracy and expand the dynamic range
of the
calculations. In an embodiment, the sinogram may be processed as integer data.
In an
embodiment, the sinogram may be processed as integer data, but the integers
are enlarged to a
sufficient size to accommodate the appropriate range of data, e.g., 64 bits,
or 96 bits, or 128 bits.
[0062] Generally in each of the following steps for processing the
sinogram, the
processing is performed on the time domain signal. In a preferred embodiment
(and as discussed
below) the probe 102 includes an acoustic lens that enables the sinogram data
to be more focused
on what is on the plane below that of the transducers ¨ the image plane. In an
embodiment, the
probe comprises an acoustic lens having a focal length of between 10 and 40
millimeters. In an
illustrative embodiment, the probe comprises an acoustic lens having a focal
length of 20
millimeters. In an embodiment, the probe may comprises an acoustic lens having
a focal length
that can be zoomed in or out, in hardware, or in software.
[0063] As discussed above, in an illustrative embodiment, each channel of
the sinogram
data represents approximately 100 millimeters of distance in the volume. The
acoustic lens
generally rejects at least some portion of a signal propagating from points
outside (e.g.,
orthogonal) to the image plane. Each transducer, however, receives signal from
substantially all
- 9 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
points of the image plane that lie within the approximately 100 millimeters
distance. The
received signal for a channel can be thought of as comprising the area of a
semicircle of radius
100 on the image plane.
[0064] Turning to Figure 2, an overview of an exemplary process is shown,
beginning
with the acquisition of three sets of data, namely, a short sinogram (step
205), a long sinogram
(step 210) and an ultrasound image (step 215), and processing the data to
produce up to six
separate images that may be useful in viewing various aspects of that acquired
data. In an
exemplary embodiment, the three sets of acquired data may be acquired using a
handheld
optoacoustic probe 102 (Figure 1). For the purposes of illustration herein, it
may be presumed
that probe 102 movement is minimal, if any, between the acquisition of the
three sets of data in
steps 205, 210 and 215. In an exemplary embodiment, a reasonable frame rate
(e.g., 10 hz),
coupled with a reasonably steady hand used in handholding the probe may yield
the three data
sets having substantially minimal movement occurring there-between. It should
be noted that the
process described herein is not limited to being used with the three
identified data sets. Use of
additional data sets, such as, for example, data sets from additional
wavelengths of light, may be
used to further improve the resulting images.
[0065] As will be discussed in more detail below, the short and long
sinogram data are
preprocessed (step 220) in one or more separate manners to reduce or
compensate for undesired
data in the sinogram, including characteristics of the measuring instrument
(e.g., the probe) or the
light used, characteristics of the volume (i.e., the tissue), characteristics
of the interaction
between the volume and the probe or light, external stimuli, or other sources.
After the
preprocessing, separate short and long images are reconstructed (step 225). In
an embodiment,
separate real and imaginary components of complex short and long images result
from the
reconstruction step. In an embodiment, the processing (step 230) of the
reconstructed images is
performed. The processing (step 230) may remove additional artifacts that can
be identified in
the reconstructed images, and in any event creates a short envelope image
(232) and a long
envelope image (234). In an embodiment, the short and long envelope images
(232, 234) are
used to generate parametric images (step 240) process. The generate parametric
images (step
240) process outputs an oxygenation map (250), a hemoglobin map (255) and a
masked
oxygenation map (260). In an embodiment, any or all of the three maps are
coregistered with,
and overlaid on an ultrasound image (step 265). A display can be provided for
display of one or
more of the displayable images displayed in steps 270, 275, 280, 285, 290 and
295. In an
- 10 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
embodiment, a group of two or more of the images may be displayed on the same
screen, and
may be commonly scaled and sized. In an embodiment, the group of all six
images may be
displayed on the same screen, and may be commonly scaled and sized.
[0066] In an embodiment, the system performing processing on the
optoacoustic data,
and/or the system displaying the optoacoustic output ¨ which may, but need not
be the same as
the system acquiring the sinogram ¨ would provide the operator the ability to
vary parameters
used in processing, when processing or viewing optoacoustic images. In an
embodiment, the
system performing processing on the optoacoustic data, and/or the system
displaying the
optoacoustic output would provide the operator the ability to switch on and
off, and potentially
vary the order of, the processing steps used to process the optoacoustic
images.
Preprocess (220)
[0067] Turning to Figure 3, an overview of an exemplary sinogram
preprocessing is
shown. After acquisition of sinogram data (step 205, 210), that data is
preprocessed (step 220,
Figure 2) in one or more separate manners to reduce or compensate for
undesired data in the
sinogram, including, without limitation, artifacts of the device itself,
artifacts of the device-
subject interaction, and external sources of unwanted information. In an
embodiment,
preprocessing may consist of one or more of the following steps: detecting bad
transducers (step
305), common mode stripe filtering (step 310), band pass filtering and/or
applying of a probe
transfer function (step 315), normalization of the dynamic range (step 320),
normalization for
energy (step 325), selective channel sensitivity (step 330), interframe
persistent artifact removal
(step 335) and software time gain compensation step (340). One or more
additional
preprocessing steps may also be used to reduce or compensate for undesired
data in the sinogram.
Notably, the steps identified in Figure 3 do not need to be performed in the
order presented, and
may be performed in any order. Moreover, not all of the steps presented in
Figure 3 are required
for any implementation of an exemplary system, rather, preprocessing consists
of the use of any
one or more steps to reduce or compensate for undesired data in the sinogram.
Preprocess (220) - Detect Bad Transducer (305)
[0068] One potential source of malady in the sinogram is a transducer
that fails to
accurately reflect the optoacoustic return signal incident thereon during the
sampling process.
The failure may be temporary, or may be permanent. Moreover, the failure may
be partial, such
as where the sampled data reflecting too high or too low a signal, or
reflecting noise, or the
-11-
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
failure may be complete, such as where the sampled data are all zeros or
nominal values. A bad
transducer could also present inconsistent or flakey output, even within a
single sinogram. Bad
transducer channels may also result, for example, from poor contact with the
tissue beneath one
or more transducer elements.
[0069] In an embodiment, when a consistently bad transducer is
identified, its identity is
noted, and thereafter the data provided from that transducer may be ignored,
replaced or
separately pre-processed. For example, in an embodiment, to compensate for the
misbehavior of
a transducer, a pre-processor is run to remove the transducer's abnormal
response characteristics.
In another embodiment, to compensate for the misbehavior of a transducer, the
transducer's data
is replaced with an average of the data from the two adjacent channels.
[0070] In an embodiment, sinogram data is analyzed for the presence of
bad channels. A
bad channel may be detected by the fact that the sinogram has a "skin" signal
¨ that is an
optoacoustic response signal reflected from at or near the surface of the
volume ¨ that is
significantly weaker than the average across the other channels. A weaker skin
signal may result
from a bad acoustic contact right above the channel or some problems, e.g.,
with electronics that
significantly reduced the gain of that channel. When a channel exhibits this
behavior, it may be
identified as "bad" and, in an embodiment, the data in that channel is zeroed
out following the
processing with a stripe filter (discussed below) to avoid artifacts.
[0071] In an illustrative embodiment, the algorithm below may be used for
identifying
bad data channels and zeroing that part of data, thereby avoiding inaccurate
image artifacts.
[0072] In this illustrative embodiment, an algorithm assumes that a
strong optoacoustic
skin signals is supposed to be received by each transducer. The strong
optoacoustic skin signal is
expected to dominate over noise and are expected to be close in magnitude from
channel to
channel.
[0073] The illustrative algorithm is described as follows: each connected
data channel is
analyzed and labeled "bad" if the average of a group of several consecutive
samples of absolute
channel data (containing the optoacoustic signal from the skin) is very small
and considered to be
a statistical outlier when compared across all the connected channels. The
outlier determination is
based on the weighted standard deviation across all the channels.
[0074] An illustrative algorithm may be executed as follows:
a. Absolute values of the signals are calculated.
b. Average values of the first several samples in absolute signals are
calculated.
- 12 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
c. Small outliers of the average values are identified using the average
across all the
connected channels minus weighted standard deviation as a threshold.
d. Identified outliers are labeled as bad channels.
[0075] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing illustrative algorithms discussed herein. The
algorithm presented is
merely an example of one way to remove bad channels that can adversely affect
the later
calculations and operations made upon the optoacoustic data. In view of the
foregoing, it will be
apparent to a person of skill in the art, and within the scope of this
disclosure, that other methods
can be used for detecting bad channels, including, without limitation, methods
that use an
autocorrelation between channels, or between sets of channels.
Preprocess (220) - Common Mode Stripe Filter (310)
[0076] Other potential sources of unwanted information in the sinogram
may appear in
the form of noise or other unwanted signal that affects all channels
simultaneously. There may
be a variety of causes of this kind of noise or unwanted signal, including,
for example, external
interference or probe characteristics. Regardless of the cause, however, the
noise or unwanted
signal may be removed or mitigated. When the sinogram is oriented with
channels
corresponding to columns, and samples according to rows, this type of filter
removes horizontal
stripes from the sinogram. In an embodiment, horizontal stripes may be removed
using a method
based on the 2-Dimensional Discrete Wavelet Transform (2D-DWT). In an
embodiment,
horizontal stripes may be removed using a method based on a frequency domain
filter (e.g., a 1-
dimensional or 2-dimensional frequency domain filter) or FIR filter. In an
embodiment, an
average across a row or other set of data is subtracted from each sample in
that row or set of data.
[0077] In an illustrative embodiment, the algorithm below may be used for
removing
horizontal stripes from a sinogram. In an embodiment, the illustrative
algorithm may be
executed as follows:
a. Precompute the sizes of the wavelet coefficients for the horizontal
coefficients at
each subband level.
b. Precompute the even-symmetric zero-phase transfer function of the
1-Dimensional (1D) frequency domain stripe filter for each wavelet subband.
c. Compute a 2D wavelet transform using the highpass and lowpass wavelet
coefficients, which may be defined by the input parameters, and by applying
forward wavelet decomposition for some number of levels.
- 13 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
d. With the vertical coefficients from each subband level, apply the 1D
transfer
function filter to each line along the vertical direction, where the 1D
transfer
function smoothly suppresses low frequencies for each of the lines.
e. Take the inverse wavelet transform by applying wavelet reconstruction to
the
modified wavelet coefficients
[0078] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in the art
in implementing this illustrative algorithm. The algorithm presented is merely
an example of one
way to implement a stripe filter to remove data that can adversely affect the
later calculations and
operations made upon the optoacoustic data. In an embodiment, common mode
stripe filtering
can be performed by using principal component analysis on the channels of the
sinogram to
remove interference that is common to each channel. In an embodiment, common
mode stripe
filtering can be performed by using principal component analysis on the
channels of the complex
analytic sinogram to remove interference that is common to each channel where
interference may
be subject to different complex phase on each channel. In view of the
foregoing, it will be
apparent to a person of skill in the art, and within the scope of this
disclosure, that other methods
can be used for removing this type of errant data.
[0079] As a wave travels along the surface of the tissue, illustratively,
the wave's crest
may meet each element of the transducer in sequence; accordingly, such a wave
may produce
diagonal artifacts in the sinogram when measurement is acquired using a linear-
array probe. In
an embodiment, the stripe filter may be used to remove these and other such
diagonal artifacts.
In an embodiment, to remove such diagonal artifacts, each channel of the
sinogram may be
shifted based on the perceived travelling speed of the surface wave prior to
application of the
stripe filter and then un-shifted after the stripe filter has been applied. In
an embodiment,
diagonal stripes may be removed using a 2D band-reject stripe filter.
Preprocess (220) - Band Pass Filter and Probe Transfer Function (315)
[0080] The acquired channels of optoacoustic return signal data captured
by the
transducers and stored in a sinogram comprise a sampling of the data the
transducers detect
(during the sampling period). As discussed above, the sinogram-resident
samples are acquired in
the time domain. As also discussed below, the optoacoustic return signal
transducer may have a
wider band than a traditional ultrasound transducer. Thus, in an embodiment,
an optoacoustic
return signal transducer may have a band width from 10 Khz or lower, to as
high as 20 Mhz or
- 14 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
more. In an illustrative embodiment, an optoacoustic return signal transducer
may have a band
width from about 50 Khz to 20 Mhz.
[0081] Selected portions of the optoacoustic return signal have been more
suitable for use
in image reconstruction. Thus, in an embodiment, portions of the optoacoustic
return signal are
eliminated without materially detracting from the resulting optoacoustic
image. In an
embodiment, a one dimensional FFT (Fast Fourier Transform) band pass filter
may be used to
reduce or remove the high and low frequency components without material
detraction from the
resulting optoacoustic image. Thus, in an illustrative embodiment, a one
dimensional FFT band
pass filter can be employed that, on the low frequency side, provides
substantially complete
attenuation at less than 10 Khz, while on the high frequency side, provides
substantially complete
attenuation after 12 Mhz. In an embodiment, a one dimensional FFT band pass
filter can be
employed that, on the low frequency side, starts to roll off at 50 Khz, while
on the high frequency
side, starts to roll of at 6 Mhz. In an embodiment, the roll off rate is
steeper for the low
frequency side than the high frequency side. Thus, in an illustrative
embodiment, a one
dimensional FFT band pass filter can be employed that, on the low frequency
side, starts to roll
off (downwardly) at 50 Khz, and provides substantially complete attenuation at
less than 10 Khz,
while on the high frequency side, starts to roll of at 6 Mhz, and provides
substantially complete
attenuation after 12 Mhz.
[0082] In addition to filtering frequency portions of the optoacoustic
return signal that
have no material effect on the resulting optoacoustic image, in an
illustrative embodiment, an
algorithm may provide an approximation of the transfer function of the probe
and the electronics,
i.e., a function that substantially approximates the system's transfer
function. As used in this
section, the system's transfer function (i.e., the function that substantially
approximates the
system's transfer function) is a transfer function that reflects at least some
of the system's own
response characteristics, such as the probe geometry, the way the probe itself
affects a light event
or the resulting optoacoustic return signal at varying frequencies, including
changes in, e.g.,
attenuation, delay, spatial response, noise or other aspects of the signal. In
an embodiment,
spatial frequency response characteristics of the tissue and/or the coupling
medium may also
affect the system's own response characteristics. The frequency domain
response characteristics,
or impulse response characteristics of the system electronics also may be
included in the system
response. Examples of the kind of response characteristics that could be
introduced by a system
response may include: filtration of frequencies such that, e.g., sound at 1
Mhz comes through
- 15 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
louder than sound at 100 Khz; delay such that, e.g., sound at 1 Mhz comes
through sooner than
sound at 100 Khz; and/or spatial effects, such that, e.g., a sound arriving at
the transducer from a
location 45 degrees from normal with respect to the transducer sounds
different than it would if it
arrived from a direction normal to the transducer.
[0083] In an illustrative embodiment, an overall system filter (i.e., a
filter to compensate
for, among other things, the system transfer function) may formed by steps
including
deconvolution of the acousto-electric impulse response, bandpass filtering,
and an additional
arbitrary transfer function to support filtration of other factors. The
sinogram data can then be
processed using the system filter function.
[0084] In this illustrative embodiment, the system's complex transfer
function is formed
out of three parts, which are later multiplied together. The first part is the
frequency domain
representation for deconvolution of acousto-electric impulse response, which
may be determined
using Wiener deconvolution with a regularization parameter that pertains to
the noise-to-signal
power spectral ratio. The second part of the transfer function is the bandpass
filter, which is
designed with a raised cosine apodization function, using provided information
on the band
pass/stop regions. The third part of the transfer function is an optional
arbitrary frequency
response. The system filter only needs to be recalculated if one of its
parameters changes.
Otherwise the filter may be determined, stored, and loaded from the storage as
needed. In short,
the sinogram data is conditioned and transformed into the frequency domain,
where it is
multiplied by the system's filter function before it is transformed back into
the time domain.
[0085] An illustrative algorithm for making the system filter may be
described as follows:
If none of the parameters were modified since the last run, the system's
transfer function is the
previously calculated input system's transfer function. Otherwise the system
filter may be
calculated according to the following steps. In step one, the deconvolution
Wiener filter is
formed. (A Wiener deconvolution filter as follows may be used:
H (f
G(f) _________________________________________
IH )11 a kf
wheref ¨ frequency (Hz), G ¨ transfer function of the filter, H ¨ system's
frequency response, a -
noise-to-signal spectral power density ratio.) In the step two, the bandpass
filter is calculated
using a raised cosine apodization function and input band pass/stop frequency
parameters. If
specified by the parameters, the bandpass filter may be unity (a constant
value of 1), and hence,
no bandpass filtering is applied. As a last step, those two complex transfer
functions are
- 16-
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
multiplied together with another defined arbitrary transfer function
(optional) to get the output
system filter function. One purpose for multiplying the two complex transfer
functions with
another defined arbitrary transfer function is to allow frequency domain
filtering that is not
readily susceptible to filtering using the other two methods.
[0086] An illustrative algorithm for processing data according to the
system filter
function may be described (for a single channel of data) as follows: The input
data is zero-padded
(or symmetrically padded) to double the length and is transformed to the
frequency domain via
the Fast Fourier Transform (FFT), complex-multiplied by the system's transfer
function, and then
the Inverse Fast Fourier Transform (IFFT) applied, to return the data to the
time domain. Once
returned to the time domain, the padding is removed.
[0087] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing this illustrative algorithm.
[0088] In an embodiment, overall system compensation may be performed and
used to
mitigate, eliminate or enhance portions of a sinogram. In an embodiment,
overall system
compensation may be used to account for situations that are not limited to
ideal lab situations or
factors based solely on the probe and the electronics; rather the
characteristics of the sinogram
may be affected by the physiology and characteristics of a typical subject and
embody non-ideal
situations that do not strictly occur in the lab. Difficult-to-model
interactions may occur in real-
world situations that differentiate in-vivo optoacoustic measurements from
models. These can
include interactions involving geometry of a probe that is part of the system;
the manner in which
the probe affects a light event caused by the system; the way in which the
probe affects
attenuation, delay, spatial response, noise or other aspects of an
optoacoustic return signal; spatial
frequency response characteristics of a tissue being imaged, and a coupling
medium used in
connection with recording the sinogram. In many cases these situations may
also be anticipated
and be replicable, though they may result from combination of factors that
would have be
unlikely to foresee even when using simulated environments, e.g., phantoms.
Accordingly, in an
embodiment, overall system compensation or calibration can encompass
accounting for these
factors by performing analysis based on a multitude of acquired datasets; the
process to
determine the overall system compensation can be based on empirically tuning
the overall system
compensation to meet a performance objective. In an embodiment, tuning can be
based on
collecting a multitude of datasets and performing a statistical regression
analysis, the objective of
the statistical regression may involve optimizing a cost function, or using
manual operator
- 17 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
adjustment; performing an offline computation to determine parameters for
computation; fitting
parameters to match the objective; determining spatial or temporal weights for
a table, the table
used in reconstruction to account for factors including geometry; or using the
statistical or
manual analysis to determine the weights of an optimal filter. In an
embodiment, the statistical
analysis may involve using specialized computer software for performing the
analysis. In an
embodiment, the statistical analysis may yield different optimal tuning
parameters for different
types of tissue or for subjects of different physiology. A method for tuning
may account for
these factors. In an embodiment, a method for tuning may have, as its
objective, the yield of
optimal results, or the enhancement of features for different tissues. For
example, enhancement
or optimal results may be sought for dense or fatty breast tissue or other
known types of tissue as
may be differentiable; likewise, enhancement or optimal results may be sought
for any types of
characteristics, including, without limitation: thick or thin layers of skin;
the mechanism by
which light is absorbed separately based on the tone of skin; the emphasis of
a tumor or lesion,
including where the tumor or lesion has different frequency characteristics
than the background
tissue; the differences between a cellular or non-cellular fibroadenoma (or
other such
determinable condition) and sets of parameters to make this more apparent
optoacoustically; the
differences between classes of malignant and benign lesions and other
indeterminate structures
yielding an optoacoustic signature (e.g. lymph nodes, fat necrosis) and a
system or method for
discriminating such; features of different scales or sizes; tuning parameters
such as packet
wavelet coefficients or vector support coefficients involving feature
detection classification; or
adjustable parameters in a deconvolution process. The method for tuning may
include acquiring
data under strictly controlled measurement conditions according to a
measurement procedure,
wherein the probe is manipulated to according to specific or specialized
motions (e.g. sweeping
or fanning) and specific portions of tissue are captured (e.g. parenchyma). In
an embodiment, the
method for optoacoustic tuning may comprise: collection of measurements;
statistical or manual
analysis involving optimizing an objective; adjusting parameters to obtain the
desired system
compensation; and applying the compensation to the sinogram thus affecting the
resulting
diagnostic overlay. In an embodiment, the compensation may be performed
separately for two or
more wavelengths. In an embodiment, the tuning analysis may be used to
generate a set of rules
that can be applied to an optoacoustic image or other system data to develop a
prognosis or
histology. The rules so generated may be applied by an operator, by the
system, or by another
system, and once applied, may provide a report of the prognosis or histology.
In an embodiment,
- 18 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
multiple sets of pre-tuned parameters may be user-adjustable or enable-able by
a user interface,
which user interface may include a set of pre-tuned parameters.
Preprocess (220) - Normalization of Dynamic Range (320)
[0089] As discussed below, time gain compensation may be applied in
hardware to
achieve higher dynamic range and/or improve the signal to noise ratio (SNR)
for a given depth or
distance. Hardware applied time gain compensation may improve the overall
dynamic range of
the optoacoustic return signal. Analog hardware applied time gain compensation
may increase
the precision of the data captured by the analog-to-digital conversion device
by amplifying low
magnitude signals from deep tissue that would otherwise not effectively use
the full bitwise
representation of the data. In addition, analog hardware applied time gain
compensation may
improve the signal-to-noise ratio by bringing weak signals at depth above an
analog noise limit in
the pathway between the hardware TGC amplifier and the analog-to-digital
conversion device.
In an embodiment, time gain compensation may compensate for the attenuation
that occurs to the
light as it transmits from a surface of a volume of e.g., tissue to areas
within the volume of tissue,
and/or for attenuation to the optoacoustic return signal as it transmits
through the volume of
tissue. In an embodiment, the image reconstruction algorithms utilized
presume, however, that
there has been no change in gain, e.g., amplifying later or deeper signals.
Accordingly, in an
embodiment, to normalize the data, the hardware time gain compensation is
mathematically
reversed, thus removing its impact from the image calculation.
[0090] In an embodiment, the sampled data is a relatively modest sized
integer, such as a
14 bit integer, which e.g., can represent values from 0 to 16,383. In an
embodiment, the data in
the sinogram is converted from integer to floating point prior to the
processing discussed in this
section; conversion from integer to floating point may be performed to
increase accuracy and
expand the dynamic range of the calculations. Generally, care should be
exercised to prevent the
loss of dynamic range when reversing the hardware time gain compensation. In
an embodiment,
the normalization of dynamic range filters the sinogram to reflect
substantially flat gain without
loss of dynamic range. It permits each sample in the sinogram to sum its
proper contribution
when used in connection with forming the resulting optoacoustic image.
[0091] In an embodiment, to renormalize the dynamic range, the time
dependent
hardware TGC curves may be factored out of each channel. In an embodiment,
hardware TGC
curves may be stored as a set of data points that are linearly interpolated by
the system firmware
- 19 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
and sent to the hardware TGC amplifier. A TGC curve may be computed from
stored data
points.
[0092] An illustrative algorithm for renormalizing the dynamic range of a
sinogram
follows: generate the TGC curve, send the TGC curve to the hardware TGC
amplifier, if
necessary, linearly interpolate the TGC curve to create a piecewise linear
curve equal in length to
the number of samples, map the computed curve from a numeric representation as
may be
required by the hardware to the amplifier gain, compute the reciprocal of the
gain curve, and
finally, multiply the corresponding samples in the reciprocal curve by the
samples of each
channel and store the result as output.
[0093] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing illustrative this algorithm.
[0094] In an embodiment, the system includes adjustable amplifiers and a
probe having
an array of transducer elements, each of the adjustable amplifiers being
associated with one or
more of the transducer elements. The transducer elements are acoustically
coupled with a
surface of a volume. The gain on the adjustable amplifiers is changed as a
function of the
passage of time during a predetermined period of time after a pulse of light.
A sinogram is
recorded by sampling the adjustably amplified plurality of transducer elements
for the
predetermined period of time. The sinogram is processed by substantially
reversing the changing
step mathematically, and storing the results in an expanded dynamic range
sinogram. The
expanded dynamic range sinogram provides sufficient numeric precision to
permit the reversal of
the changing step without materially decreasing the dynamic range of the
information in the
sinogram. An optoacoustic image is generated based upon the information
contained in the
expanded dynamic range sinogram.
[0095] The function of the passage of time noted above may account for at
least one of:
acoustic wave propagation attenuation of tissue, optical fluence attenuation
of tissue and
geometry of the plurality of transducer elements. The process of generating an
image may
include generating a complex-valued array that includes an analytic
representation of the
expanded dynamic range sinogram, an imaginary component of the complex-valued
array
representing a quadrature, and a real component of the complex-valued array
representing an in-
phase component. The optoacoustic image may be generated based upon the
complex-valued
array, the optoacoustic image being a positive, real valued, non-complex
image. The quadrature
component may be formed by computing the Hilbert transform of the real
component. Processing
- 20 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
of the sinogram may include generating at least one time gain compensation
curve reflecting the
changing gain on the adjustable amplifiers as a function of the passage of
time, computing a
reciprocal of the mapped time gain compensation curve, and multiplying
corresponding samples
in the reciprocal time gain compensation curve by samples of each of a
plurality of channels of
data in the sinogram. The processing step may further include the step of
mapping the time gain
compensation curve from logarithmic units into linear units. The step of
generating a time gain
compensation curve may include generating a complex-valued array comprising an
analytic
representation of the expanded dynamic range sinogram, the imaginary component
of the
complex-valued array representing a quadrature, and a real component of the
complex-valued
array representing the in-phase component. The generating step may also
include generating an
optoacoustic image based upon the complex-valued array, the optoacoustic image
being a
positive, real valued, non-complex image. Each adjustable amplifier may be
associated with one
of the transducer elements, or may be associated with two or more of the
transducer elements.
Preprocess (220) - Energy Normalization (325)
[0096] In an embodiment, the sinograms contain optoacoustic return signal
data
correspond to a single light event such as the firing of a laser. In use, the
system 100 may
produce a plurality of sinograms, each corresponding to a separate light
event. For example, in
an embodiment, a single light source can be used repetitively, with the system
generating a
separate sinogram to capture optoacoustic return signal data from each. In
another embodiment,
two or more light sources can be used to generate discrete light events, such
as, for example, by
interleaving them so that one is used and then the other, with the system
generating a separate
sinogram to capture optoacoustic return signal data from each. In an
illustrative embodiment, an
ND:YAG laser and an Alexandrite laser are used in an interleaved manner, with
one causing a
light event and then the other. In each of the foregoing multiple light event
situations, the energy
of one light event may deviate from the total energy of another. Deviation
from one light event
to another may, or may not be intended, and may be the result of external
influences or system
design or a combination of factors. For example, most lasers fluctuate in
energy, at least to some
degree and often to a large degree, each time they are used in the manner
described in more detail
below.
[0097] Regardless of the cause, in an embodiment, it may be desirable to
reduce or
eliminate the shot-to-shot variance. Such shot-to-shot variance can, for
example, create problems
in using the sinogram data to produce consistent images. Moreover, when images
are shown in
-21 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
sequence, shot-to-shot variance can cause flicker, not unlike that seen in an
old time movie. As a
result, shot-to-shot variance can inhibit or prevent adequate review of image
sequences, or inhibit
or prevent adequate interpretation of images created by different lights in
two separate light
events such as of the image pairs created using an ND:YAG laser and an
Alexandrite laser as
discussed.
[0098] In an embodiment, energy normalization can be accomplished by
dividing each
sample by a value proportional to a measured energy of the light event so that
each sample in the
sinogram would thereafter represent a normalized value. In an embodiment,
energy
normalization can be used in conjunction with a calibration procedure, for
example, by setting
the initial energy of laser output to a specified level and normalizing the
energy deviation against
that level.
[0099] In an embodiment, an optoacoustic imaging system includes a
handheld probe and
first and second pulsed light sources having a common output. The first and
second light sources
generate pulses of light at first and second predominant wavelengths,
respectively. The handheld
probe includes an ultrasound transducer array having an active end located at
the distal end of the
handheld probe for receiving an optoacoustic return signal. A sensor measures
a portion of the
light transmitted along the light path. A data acquisition samples the
ultrasound transducer array
during a predetermined period of time after a pulse of light from the first
light source and during
a predetermined period of time after a pulse of light from the second light
source. The sampled
data is stored. An image processing unit reconstructs a first optoacoustic
image based on the
sampled data corresponding to a pulse of light from the first light source and
reconstructs a
second optoacoustic image based on the sampled data corresponding to a pulse
of light from the
second light source. An energy normalizing unit computes a normalization
factor based on a
measurement from each sensor in the array and applies the normalization factor
to data
corresponding to the pulse of light. The energy normalization unit may
comprise, for example,
the computing subsystem 128 (FIG. 1), the computer, the optoacoustic
processing and overlay
system 140 (FIG. 1), the digital acquisition and processing board 2818 (FIG.
28), and/or any
other electronics capable of digital signal processing.
[00100] In an embodiment, the sampled data is stored in a sinogram, and
the energy
normalizing unit applies the normalization factor to data stored in a
sinogram. The normalization
factor may be computed, for example, by dividing a nominal light source energy
by the
measurement from the sensor times a constant, and may be applied by
multiplying each sample
- 22 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
in the sinogram by the normalization factor. The energy normalizing unit may
be programmed to
apply the normalization factor to the reconstructed image. The sampled data
may be processed
prior to being reconstructed into an optoacoustic image, and the energy
normalizing unit may be
programmed to apply the normalization factor to processed sampled data. The
sensor that
measures a portion of the light transmitted along the light path may be
adapted to measure light
reflected by the optical window, and may comprise a sensor input that is
filtered using an optical
filter. Such optical filter may be adapted to provide more attenuation at the
second predominant
wavelength than at the first predominant wavelength.
[00101] In an embodiment, the system includes first and second sensors to
measure at least
a portion of the light. The first sensor measures light having a first
predominant wavelength
transmitted along an auxiliary light path, and the second sensor measures
light having a second
predominant wavelength transmitted along the auxiliary light path. The first
and second sensors
may be adapted to measure light reflected from the optical window. The first
and second sensors
are the same sensor. The auxiliary light path may be configured to direct
light from the common
output to the first and second sensors. The main light path and the auxiliary
light path may be
common. A data acquisition unit may be provided for sampling the ultrasound
transducer array
during a period of time after a pulse of light and for storing the sampled
data as a sinogram. A
data processing unit may be provided for reconstructing an optoacoustic image
based on sampled
data stored as a sinogram, the data processing unit. In this respect, the data
processing unit can
include software for computing a normalization factor based on a measurement
made by at least
one of the first sensor and the second sensor during a pulse of light and
applying the
normalization factor to data corresponding to the pulse of light. The data
processing unit may
comprise, for example, the computing subsystem 128 (FIG. 1), the computer, the
optoacoustic
processing and overlay system 140 (FIG. 1), the digital acquisition and
processing board 2818
(FIG. 28), and/or any other electronics capable of digital signal processing.
[00102] The data processing unit may include software for generating a
complex-valued
array comprising an analytic representation based on data stored as a
sinogram, an imaginary
component of the complex-valued array representing a quadrature, and a real
component of the
complex-valued array representing an in-phase component. The data processing
unit may
additionally include software for reconstructing the optoacoustic image based
upon the complex-
valued array, the optoacoustic image being a positive, real valued, non-
complex image. The data
processing unit may additionally include software for generating a map overlay
based on at least
- 23 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
portions of two optoacoustic images, the map overlay being reflective of areas
within at least a
portion of the images which have a difference in absorption in response to the
different pulses of
light. The data processing unit may also include software for generating
another map overlay
based on at least a portion of the two optoacoustic images, the another map
being reflective of
areas within at least a portion of the images which have stronger absorption
in response to both
pulses of light than other areas within the images. The data processing unit
may further include
software for generating a mask reflective of a combination of information in
the map and
information in the another map, the mask adapted to exclude areas of an image,
and for
generating a masked parametric map by applying the mask to an auxiliary map,
thus forming a
parametric map. The auxiliary map may be another map and/or an image.
[00103] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing this illustrative algorithm.
Preprocess (220) - Selective Channel Sensitivity (330)
[00104] The sinogram data may contain variations that are related to the
performance of
specific components of the system. Such variations can cause inaccuracy and/or
unwanted or
undesired results in images reconstructed therefrom. In an embodiment,
information is stored
concerning such variations and the information is used to process the sinogram
and remove
variations that are related to the performance of specific components of the
system such as a
channel-to-channel variation. In an embodiment, the channel sensitivity
process may be
performed in a manner to account for variations in signal strength resulting
from signal variation
related to contact, the coupling medium and other such issues (e.g., performed
adaptively or
dynamically). In an embodiment, dynamic compensation may be performed by using
channels in
close proximity to each other, which may be presumed to have similar content,
to determine a
dynamic compensation factor of each channel. In an embodiment, the sinogram is
filtered prior
to performing dynamic selective channel sensitivity.
[00105] In an illustrative embodiment, an optoacoustic device comprises a
probe having
128 or 256 transducer elements. Each of the transducer elements are
electrically connected to
one amplifier. Each of the amplifiers may handle, e.g., 8 individual
transducers, thus, a total of 7
or 8 amplifiers may be required in this illustrative embodiment. A DAP board
(i.e., data
acquisition processor board) may contain 8 such amplifiers, and thus be used
to acquire data from
all 128 or 256 transducer elements. Variations may occur between the response
of the several
transducer elements. Generally, for example, each amplifier has a single gain
control that may
- 24 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
affect the gain on all 8 transducers it is handling. Accordingly, if one or
more of the transducer
elements responds differently, e.g., more quietly, than the other transducer
elements connected to
the same amplifier, it cannot be compensated for using the gain control.
Similarly, variations
may occur between the response of the several amplifiers, leading to variation
in what would
otherwise be identical transducer element responses. Variations in may also
occur due to the
amount of pressure applied to the probe, including different amounts of
pressure being applied to
different regions or elements on the probe. Variation may additionally occur
due to the quality or
amount of skin or surface contact with the probe, or the amount of coupling
medium used.
Surface features, such as roughness, physiological structures near the
surface, or focusing
aberrations may also produce variations in the signals received on a per-
channel basis. In an
embodiment, variations can be detected using an automatic method or a fixed
method that is
determined by measuring and calibrating a particular transducer.
[00106] In an embodiment, calibration data for a probe indicative of the
relative or
absolute performance of the transducer elements may be maintained. Similarly,
calibration data
for a DAP board indicative of the relative or absolute performance of the
amplifiers may be
maintained. Such calibration data may be acquired at the factory at
manufacture time by using
known inputs or tests, or alternatively, may be acquired later, e.g., in the
field, using calibration
equipment. A "dummy" probe that is calibrated to transmit specific output
signals may be used
to help determine calibration information for the amplifiers. A known phantom
may be used to
help determine calibration information for the transducer elements. In an
embodiment, the probe
holder contains an object having a known acoustic or optoacoustic response
that can be used to
run calibration tests, or to confirm that the system is functioning in a
consistent manner.
[00107] In an embodiment, a test sample is provided that is expected to
produce a given
output X from each transducer element. When the test sample is tested, the
response from most
channels is indeed X, but from several channels is 0.9X, and from one channel
0.85X. In an
embodiment, the sinogram column corresponding to the 0.9X channels are
enlarged by a factor
of 1/0.9, while the sinogram column corresponding to the 0.85X channel is
enlarged by a factor
of 1/.85. Where a channel responds with 1.1X it can similarly be multiplied by
a factor of 1/1.1.
[00108] The foregoing presumes that any channels that differ from the
expected output
will do so in a linear manner. Where this presumption is insufficient to
accommodate the actual
deviation, a more complex transfer function can be used to compensate for the
actual sensitivity
of a channel.
- 25 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Preprocess (220) - Interframe persistent artifact removal (335)
[00109] For the purpose of the following discussion, the optoacoustic
return signal data
can be thought of to include three components: the desired coupled response;
the undesired
coupled response; and noise. Interframe persistent artifact as used in this
section refers to the
undesired coupled response, not to other noise. Unless compensated for,
interframe persistent
artifacts may be present in images created from an optoacoustic return signal
created using a
handheld probe that provides both the light and the transducer elements. The
interframe
persistent artifact is generally not the same from one tissue or volume to
another, however, a sub-
component of the interframe persistent artifact may remain the same between
all data collected
using a given set of hardware, or even a given probe. More generally, while
two similar
phantoms may create similar interframe persistent artifacts, tissue creates
different interframe
persistent artifacts than a phantom, and one person's tissue creates different
interframe persistent
artifacts from another person's tissue. Moreover, generally, the amount of
interframe persistent
artifacts present in most common phantoms may be lower than, or different
than, the interframe
persistent artifacts present in most tissue.
[00110] It has been found that interframe persistent artifacts are
relatively stable for a
given individual, and more so, when collecting data around nearby locations.
Thus, for example,
the shot-to-shot variance in interframe persistent artifacts are relatively
low shots of a single
individual, but relatively much higher for shots of different individuals. The
interframe
persistent artifacts may also remain relatively stable when similar amounts of
coupling medium
are used, and where the pressure applied to the probe, and thus the probe
contact, remains
consistent. A method of mitigating interframe persistent artifacts from
sinogram data comprises
the removal of common data from separate, spatially distinct frames. In an
embodiment,
common data can be removed from separate, spatially distinct frames using
singular value
decomposition (SVD) algebra, principal component analysis (PCA), or other
similar methods.
In an embodiment, common data can be removed from separate, spatially distinct
frames using a
principal component removal algorithm. Typically, the singular value
decomposition and
principal component removal will require a sufficient number of independent
frames where the
interframe persistent artifact remains substantially constant and the
collected data is changing and
uncorrelated at a given sample or pixel. In an embodiment, more than 3
uncorrelated frames, and
preferably more than 20 to 30 frames form the data set for analysis to remove
the interframe
- 26 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
persistent artifacts. In an embodiment, at least about 50 frames are analyzed
in connection with
an algorithm to remove interframe persistent artifacts.
[00111] In an embodiment, Interframe persistent artifact removal is
performed on a per-
light-source basis, meaning that where, for example, both YAG and Alexandrite
lasers are used
for different frames, YAG frames only are analyzed for Interframe persistent
artifact removal
from the YAG frames, and Alexandrite frames only are analyzed for Interframe
persistent artifact
removal from the Alexandrite frames. It should be noted that the expression
per-light source is
substantially directed at the wavelengths for the light source. Generally,
lasers do not operate at
a single wavelength, but rather, lasers produce light in a narrow range of
wavelengths, often
characterized by a dominant wavelength, which wavelength is used as a
reference to for that
laser. Thus, for example, a Nd:YAG laser output is often tuned to, and
described as a 1,064 nm
wavelength, not because the laser output is solely and precisely at that
wavelength, but rather,
because that is its predominant wavelength of light output. Similarly, an
Alexandrite laser,
which can be tuned to a variety of wavelengths from about 700 to 820 nm, and
as used herein is
generally tuned to, and often described as a 757 nm wavelength, is not
intended to describe a
precise wavelength, but rather a predominant wavelength in a narrow-band
output of such a laser.
Accordingly, as the term "per-light-source basis" is used above, if a tunable
(rather than pre-
tuned) laser were used, it would be considered one light-source for all frames
created at
substantially the same wavelength setting.
[00112] In an embodiment, where the total light energy for each frame is
known or can be
estimated, it may be advantageous to perform Interframe persistent artifact
removal on frames
having similar total light energy. Thus for example, in an embodiment,
Interframe persistent
artifact removal may be performed on a per-light-source basis for frames
having more than
average light energy, separately from the frames having less than average
light energy. In an
embodiment, the frames for a given light-source are divided into a plurality
of groupings based
on the total light energy for the frame, and Interframe persistent artifact
removal is performed on
each of the plurality of groupings. In an embodiment, the plurality of
groupings is determined
based on dividing the frames equally into the desired number of groupings,
i.e., 1/3 in the first
group, 1/3 in the second group, 1/3 in a third group. In an embodiment, the
total light energy for
the frames can be analyzed and the frames divided statistically, with those
falling within a
statistical grouping being analyzed together. For example, frames having total
light energy of
within one standard deviation of the mean may fall into a first category,
frames more than one
-27 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
standard deviation above the mean fall into a second category and the
remainder fall into a third
category.
[00113] In an embodiment, an estimate of the interframe persistent
artifacts is created from
an average for each sample, for each channel, across a relatively large set of
sinograms, e.g., 50
or more. In an embodiment, an estimate of the interframe persistent artifacts
for each wavelength
is created from an average for each sample, for each channel, for a given
wavelength, across a
relatively large set of sinograms, e.g., 50 or more. In an embodiment, the
sinograms forming the
set comprising the estimate set are spatially distinct from each other ¨ i.e.,
captured from a
differing regions of tissue. In an embodiment, each sinogram being a candidate
for addition to
the set of sinograms used in forming the estimate is rejected if it is not
spatially distinct from the
previous sinogram. In an embodiment, a test is run on a frame to ensure that
it is spatially
distinct from the previously used frame before it is mathematically embodied
in the estimate. In
an embodiment, the estimate is updated with each subsequent frame, or each new
frame for the
given wavelength. In an embodiment, the estimate is updated with a
predetermined number of
new frames (or new frames for the wavelength), and then remains consistent for
the reading, or
for some longer period. In an embodiment, the estimate is updated with each
subsequent frame,
or each new (spatially distinct) frame for the given wavelength. In an
embodiment, the estimate
is updated with a predetermined number of new (spatially distinct) frames (or
new (spatially
distinct) frames for the wavelength), and then remains consistent for the
reading, or for some
longer period.
[00114] In an embodiment, the estimate is updated using a moving window of
frames
representing a fixed number of the most recent frames taken in a reading. In
an embodiment, an
estimate for a specific individual is associated with that individual and
retained for future use
with the individual. In an embodiment, as estimate for a specific individual
created with a given
probe is associated with both the individual and the probe, and retained for
future use with the
same individual and probe.
[00115] In an embodiment, the detection of motion of the probe is used to
discriminate and
ensure that the frames collected for estimating the interframe persistent
noise are independent or
not correlated; i.e., when zero or little motion is occurring, the frames are
correlated. In an
embodiment and automatic motion detection algorithm may be performed on a
sinogram, or on a
reconstructed image, to determine if motion is occurring. In an embodiment,
phase correlation
may be used on two or more reconstructed images to determine the extent of
motion that has
-28-
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
occurred there-between. In an embodiment, a frequency-domain filter may be
applied to two or
more sinograms or images, and the correlation or difference between frames,
may be used to
determine if substantial motion has occurred between the frames; the more
similar the frames, the
less motion that has occurred. In an embodiment, low frequencies may be
filtered out prior to
motion detection since dominant interframe persistent artifacts are found in
lower frequencies,
whereas many structures in the tissue, such as blood vessels and tissue
boundaries correspond to
higher frequencies. In an embodiment, the interframe persistent noise estimate
may be filtered in
the frequency domain (or in another domain) to prevent structures such as the
skin layer - which
remain constant but is not considered unwanted - from inadvertent removal.
[00116] In an embodiment, where a "live" display is provided, an estimate
can be formed
using a plurality of prior frames. In an embodiment, where a "live" display is
provided, an
estimate can be formed using a plurality of prior spatially distinct frames.
In an embodiment,
where a "live" display is provided and the system comprises a satisfactory
frame rate, the
estimate can comprise past frames and future frames, provided that the display
is delayed in time
to permit the use of such frames. Thus, for example, where the frame rate for
a given laser is,
e.g., 5 frames per second, and the display is about one second behind real
time, it may be
possible to use four or five "future" frames to estimate the interframe
persistent artifacts in the
current frame. It will be apparent to one of skill in the art that "future"
frame data can be
incorporated into an estimate where the display is provided in an offline
(e.g., non-live) playback
system.
[00117] In an embodiment where a display output is provided after a
reading is complete,
all of the spatially distinct frames (or all of the spatially distinct frames
of a give wavelength) can
be used in creating a post-reading estimate of interframe persistent
artifacts, and then entire
reading can be reconstructed and output with the post-reading estimate of
interframe persistent
artifacts eliminated from the sinograms prior to their reconstruction.
[00118] In an embodiment, interframe persistent artifact estimation and
removal is
performed post-reconstruction, on the reconstructed image, or on an
intermediate image formed
after reconstruction, rather than performing this step on the sinogram data.
In an embodiment,
interframe persistent artifact estimation and removal is performed post-
reconstruction on the real,
imaginary or both components of complex images reconstructed from complex
sinograms;
complex images and sinograms are discussed in more detail below.
- 29 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00119] In an embodiment, the estimate of interframe persistent artifacts
is used as a basis
to modify sinograms prior to image reconstruction. In an embodiment, the
estimate of interframe
persistent artifacts is used to subtract artifacts out of the sinogram prior
to image reconstruction.
[00120] In an embodiment, an estimate for the interframe persistent
artifact can be
computed by using the first principal component of the independent analysis
frames. In an
embodiment, independent component analysis can be used to estimate the
interframe persistent
artifact from the independent analysis frames in a similar fashion.
[00121] The following processing steps are illustrative of an embodiment
of the Interframe
persistent artifact removal algorithm.
a. compute the interframe persistent artifact estimate;
b. compute the scalar product "P" of the interframe persistent artifact
estimate on the
input data containing the artifact;
c. from each element of the input, subtract the projection of the
interframe persistent
artifact on the input from the input, by subtracting each corresponding
element in
the interframe persistent artifact estimate multiplied by P from the input and
storing the result in the output.
[00122] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing this illustrative algorithm.
Preprocess (220) - Software Time Gain Compensation (340)
[00123] After a light event in tissue produces sound via an optoacoustic
effect, the sound
attenuates as it travels through the surrounding tissue. As the acoustic wave
propagates through
the tissue, its energy is absorbed by the tissue. In general, the further the
sound has traveled, the
more of its energy will have been lost, i.e., into the tissue or other
propagation medium. In
addition, the longer it takes sound to reach the transducer, the father it has
traveled (assuming a
constant speed of sound). For example, in the illustrative embodiment above,
more than 2,000
samples are taken at a frequency of 31.25 Mhz, thus sampling for about 65
microseconds of
time, which corresponds to a distance of somewhere around 100 millimeters,
depending on the
speed of sound in the particular tissue. Thus, later samples in the sinogram
have greatly
attenuated high frequencies as compared to the earlier samples, which have
less attenuated high
frequencies. The tissue structures and material constituents of the
propagating medium
(including, e.g., the acoustic lens and/or transducers), as well as physical
boundaries or layers
found within the medium may play a role in the attenuation, and thus the
received energy of the
- 30 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optoacoustic return signal. In an embodiment, attenuation in an homogenous
medium can be
modeled as an exponential decay curve (e.g., as ideal), but the degree to
which this holds true
depends on the particular tissue or other volume being imaged. In an
embodiment, compensation
is performed on a per channel basis. In an embodiment, the samples are
amplified by a factor
related to the time they were received.
[00124] An illustrative embodiment of the software time gain compensation
algorithm is
provided below:
a. Compute a 1D compensation curve based on a function of time
corresponding to
the sample number in the measured channel data. (In an embodiment, the 1D
compensation curve may be based on an exponential decay curve with nominal
acoustic attenuation corresponding to the one-way propagation of the acoustic
wave from the optoacoustic source to the transducer.)
b. For each channel in the sinogram
i. Multiply each sample in the input sinogram by the corresponding
compensation value in the 1D compensation curve
ii. Place the resultant multiplied value into the output sinogram at the
corresponding sample and channel
[00125] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing this illustrative algorithm.
Preprocess (220) - Sub-band Acoustic Compensation (345)
[00126] Typically, as between the higher and lower frequencies information
contained in
the optoacoustic return signal, the higher frequencies may correspond to
smaller sources and
boundaries, and the lower frequencies may correspond to larger sized objects.
During acoustic
wave propagation in tissue, however, higher frequencies typically attenuate
more and lower
frequencies typically attenuate less. In other words, higher frequency
acoustic waves are more
attenuated than lower frequency acoustic waves traveling the same distance,
and thus, received at
(or near) the same time. This difference in attenuation can create distortion
in a reconstructed
optoacoustic image. Moreover, the higher frequency acoustic waves travel in
tissue at a
somewhat differing rate than lower frequency acoustic waves counterparts.
Accordingly, to
provide more accurately reconstructable data (e.g., sinogram), compensation
may be made for
time on a per frequency basis, and for amplitude on a per time basis.
-31 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00127] To perform compensation for frequency dependent attenuation, the
higher
frequency information may be amplified, or may be amplified more than lower
frequency
information. In an embodiment, such amplification may be performed by applying
compensation
separately to sub-bands of the data, each sub-band corresponding to a filtered
range of
frequencies from the data. Applying the compensation to sub-bands rather than
individual
frequency components reduces computational load, and thus the need for
computational
resources. In an embodiment, in each sub-band, older samples (i.e., samples
received later in
time) are amplified more than newer samples. Compensation values can be
estimated for tissue
generally, or for specific tissue of interest, by measuring attenuation and
speed of sound in tissue
samples at varying frequencies.
[00128] Thus, in an embodiment, frequency domain sub-bands are identified
which
associate sub-band compensation factors, approximately, to the frequency
dependent attenuation
of the signal. In an exemplary embodiment of a sub-band acoustic compensation
method, the
compensation factors associated with a particular sub-band may be calculated
in relation to depth
and the center frequency associated with the sub-band. In an embodiment, to
account for effects
of depth related distortion as a function of a particular depth, d, and center
frequency, fc, the
compensation factor f(d, fc) may be calculated as f(d, fc) = exp(d* fc /
1,000,000). In an
embodiment, the compensation factor f(d, fc) may be calculated as f(d, fc) =
exp(d* fc A g / a0),
where g and a0 are parameters. In an embodiment, g equals 1.0 and a0 equals
1,000,000. In
another embodiment, g and a0 are configurable parameters. In an embodiment,
the system
performing processing on the optoacoustic data, and/or the system displaying
the optoacoustic
output ¨ which may, but need not be the same as the system acquiring the
sinogram ¨ would
provide the operator the ability to vary the g and/or a0 parameters when
processing or viewing
optoacoustic images.
[00129] The following processing steps are an illustrative embodiment of a
Sub-band
Acoustic Compensation (345) algorithm as implemented to process sinogram data:
a. Compute a list of frequencies corresponding to each sample in the frequency
domain.
b. Compute an array corresponding to the distance of an optoacoustic source to
a
transducer pertaining to each sample in the received optoacoustic signal. This
may be done by multiplying the known time delay for each sample (i.e., based
- 32 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
upon when it is received) with the nominal speed of sound for the volume of
tissue.
c. Compute a sub-band filter for each sub-band.
d. Create an array to store an output sinogram and initialize each element to
zero.
e. Compute the Fourier transform of the input sinogram for each channel to
create
the frequency domain data
f. For each sub-band filter, for each channel,
i. multiply the frequency domain data by the sub-band filter
ii. compute the inverse Fourier transform of the result
iii. multiply the result element-wise by the compensation factor for the sub-
band
iv. accumulate the result in an output sinogram
[00130] In processing the optoacoustic return signal, information in the
signals from as
much of the acoustic spectrum as may be detected by the transducer may contain
potentially
valuable information concerning the volume of tissue. Thus, in an embodiment,
(as discussed in
more detail below) the transducer used to receive the optoacoustic return
signal is sensitive to a
broad band of acoustic frequencies. Because of the broadband sensitivity,
certain undesired
information may also be captured in the optoacoustic return signal, including,
without limitation,
electronic interference, acoustic interference and mechanical interference.
This undesired
information is not easily identified in, and thus not easily filtered out of,
the optoacoustic return
signal. Furthermore, frequency dependent attenuation and the frequency
dependent speed of
sound are more pronounced in the optoacoustic return signal because of the
broadband nature of
the transducer sensitivity.
[00131] Because of its wideband nature, in an embodiment, the optoacoustic
return signal
is subjected to one or more techniques to process distortions across all
frequencies. In an
embodiment, some narrowband simplifications may be applied to optoacoustic
data in sub-bands,
where such simplifications may not prove reasonable for the entire wideband
optoacoustic return
signal.
[00132] Thus, in an embodiment, a Sub-band Acoustic Compensation (345)
algorithm may
employ a narrowband simplification of having fixed acoustic attenuation
coefficient; although
the simplification would not be valid across the broadband optoacoustic return
signal, the
algorithm can apply this simplification separately for each of the sub-bands.
In another
- 33 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
embodiment, a narrowband simplification can be performed by computing a small
time shift
between two demodulated narrow-band signals in the time domain; the shift
being found by
using phase of the inner product of the two complex signals rather than using
a less efficient
computation involving normalized moments of the cross-correlation function.
Other narrowband
simplifications may also be employed after breaking the optoacoustic return
signal into a
plurality of sub-bands, such simplifications reducing the computational load
required for
processing the optoacoustic return signal. Following is an illustrative
embodiment of a method
for applying narrowband simplifications to optoacoustic data:
i) a filter baffl( of multiple filters can be formed to encompass a set of
sub-bands of
the frequency domain so that the energy summation (i.e., the sum of the
squares)
of the filters for each frequency will have a constant value of one (i.e.
"partition of
unity" property of the filter baffl( in the frequency domain), and, each
filter in the
filter baffl( may conform to a band-limited frequency range, thus, in context,
the
filter being referred to as a sub-band filter;
ii) each sub-band filter from the filter bank is applied separately to the
optoacoustic
return signal to create a filtered representation of the optoacoustic data for
each
sub-band;
iii) a narrow-band simplification is applied separately to each filtered
representation
of the optoacoustic data to create processed data for each sub-band;
iv) the processed data for each sub-band may then be re-assembled, with the
processed data for the other sub-bands, into a final processed form, the re-
assembly comprising additively combining the contributions from all of the
processed data for each sub-band.
[00133] In an embodiment, a narrowband simplifications may be applied to
optoacoustic
data by using a wavelet packet transform which uses convolutional cascaded
filter banks and
downsampling operations. In an embodiment, the wavelet packet transform may be
a dual-tree
complex wavelet packet transform. In another an embodiment, narrowband
simplifications may
be applied in the time domain on demodulated filtered sub-bands where the
demodulation is
performed directly in the frequency domain. Where narrowband simplifications
are applied in
the time domain on demodulated filtered sub-bands, arbitrary sub-band filters
may be used. In an
embodiment, the system performing processing on the optoacoustic data, and/or
the system
displaying the optoacoustic output ¨ which may, but need not be the same as
the system
- 34 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
acquiring the sinogram ¨ may provide the operator the ability to vary the sub-
band filters used in
the narrowband simplification, when processing or viewing optoacoustic images.
In an
embodiment, applying the processing method using a suitable narrowband
simplification may
reduce the amount of necessary computation.
[00134] In an illustrative embodiment, an optoacoustic data processing
method is
described below, where the narrowband simplification is performed in the time-
domain on data
demodulated in the frequency domain. In an embodiment, the FFT size of the sub-
bands can be
significantly smaller than the FFT size of the full signal, by having a
significantly smaller FFT
size in the sub-bands, processing may be substantially faster, while achieving
substantially the
same result. The following processing steps are illustrative:
a. if appropriate, pad the signal with zero padding or symmetric padding
(optional);
b. convert the input signal to the frequency domain;
c. remove the "negative" frequencies (i.e. in the range [¨fs/2, 0-]) and
double the
"positive" frequencies (i.e. in the range [0+, fs/2]) to create an analytic
signal in
the frequency domain;
d. for each sub-band, create a temporary complex-valued array filled with
zeros,
with a length of at least twice the bandwidth of the corresponding sub-band
filter
to store the demodulated signals in the frequency domain. Ideally, the length
of
the temporary array will be much less than the original frequency domain
signal,
and thus, corresponds to a downsampling operation;
e. for each sub-band, copy the values of the positive frequency
coefficients in the
frequency-domain signal (within a range that encompasses the first non-zero
value of the sub-band filter to the last non-zero value of the sub-band
filter) into
the corresponding temporary array, such that a frequency domain demodulation
is performed by aligning the lowest frequency component of the copied range
with the position of the DC frequency component in the temporary array, (note
that the temporary array will contain zeros for coefficients corresponding to
negative frequency components), the temporary array may also be padded with
additional zeros beyond the range of copied frequency components
corresponding to time domain interpolation, which may further increase the
- 35 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
number of samples in the demodulated signal so the length is an optimal power-
of-two for fast Fourier transformation;
f. with each sub-band, apply the sub-band filter to the corresponding
temporary
array by multiplying the sub-band filter values with the temporary array
values
corresponding to the aligned frequency components, and storing the result in
the
temporary array as the frequency domain demodulated signal;
g. convert each frequency domain demodulated signal to the time domain using
the
inverse fast Fourier transform (IFFT);
h. apply the narrowband simplification in the time domain to each time domain
demodulated signal;
i. covert each time-domain demodulated signal back to the frequency domain by
applying the fast Fourier transform (FFT);
j. modulate and sum each processed signal together in the frequency domain and
store the result as a new full-length frequency domain signal (the modulation
may be performed implicitly by aligning the frequency domain values of the
processed signal with the positive frequency component positions corresponding
the original full-length frequency domain signal);
k. perform the inverse Fourier transform on the resulting frequency domain
signal;
1. if padding was used, remove the padding.
[00135] The time domain signal resulting from the foregoing method is the
output of this
embodiment of a method of applying a narrowband simplification to an
optoacoustic data
processing.
[00136] When using sub-band methods, demodulated signals may leak into
other sub-
bands. Such leakage may cause distortion and aliasing. The prevention of
leakage each
demodulated signal into other sub-bands may reduce distortion, aliasing and/or
maintain
partition-of-unity for mathematical reasons. To mitigate leakage, then an
additional step may be
applied for each processed demodulated sub-band in the frequency domain prior
to performing
an FFT transform, namely, either:
a. apply a multiplicative windowing filter (e.g., the original filter
bank filter, or an
inverse for such filter); or
- 36 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
b. apply a thresholding shaping function such that the magnitude of each
complex
coefficient will not exceed the value defined by the shaping function for each
coefficient.
[00137] In an embodiment, a wavelet packet transform or a the dual-tree
complex wavelet
packet transform (DTCWPT) algorithm may be applied, an thus, a cascaded filter
baffl(
implementation can be used rather than operating directly in the frequency
domain. The
following steps illustrate such an embodiment:
a. apply the wavelet packet transform;
b. apply a narrow band simplification to time-domain sub-band; and
c. then apply the inverse wavelet packet transform.
[00138] In an embodiment, a spectrogram or another method of time-
frequency domain
processing can be applied to the narrow-band simplification rather than sub-
band filters. Use of a
spectrogram uses time-domain based windowing rather than sub-band filters.
Regardless of
whether time-domain based windowing or sub-band filters (e.g., frequency based
windowing) is
employed, a Sub-band Acoustic Compensation (345) algorithm may implemented to
process the
optoacoustic data (e.g., sinogram data) to reduce complexity and permit narrow-
band
simplification.
[00139] Pseudo-code in the Appendix will provide additional details of an
illustrative
embodiment of a Sub-band Acoustic Compensation (345) algorithm.
Preprocess (220) - Transform Operator (350)
[00140] As discussed in more detail in the reconstruction section below,
for a variety of
reasons, the two dimensional sinogram data as discussed herein is not
susceptible to closed form
reconstruction. In an embodiment, a transform operation is performed in
advance of or during
reconstruction. The transform operation is used to yield more accurate
results. In an
embodiment, the transform operator can be used to account for the geometry of
the system using
the propagation model of the Helmholtz equation to approximate a closed form
inversion
formula, thereby yielding an accurate numerical results for the case of ideal
reconstruction. In an
embodiment, the transform operator may consist of discrete operations to match
or resemble
mathematical operations inside of the integrand of a closed-form inversion
equation, or a similar
equation, for the system geometry. In an embodiment, the transform operator
may be separated
from the weights of the equation because both the transform operator and the
weights may be
tuned separately. In an embodiment, a tuning procedure of the transform
operator and of the
-37-
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
weights may be carried out by comparison to a phantom, or to tissue, and
identifying
(subjectively or objectively) the best result. In an embodiment, a tuning
procedure of the
transform operator and of the weights may be carried out by comparison against
a known
equation, matching the weights to the transducer and patient geometry, typical
fluence, etc.
[00141] In an embodiment, a transform operator may implemented by the
following
equation:
vout(t)=a(t) d/dt [ b(t) vin(t) ],
where vin(t) is the input signal, vout(t) is the output signal, d/dt is a
derivative operation, and a(t)
and b(t) are constant functions. In an embodiment, a(t) = (t)2 and b(t) =
1/(t) to approximately
represent a simplification for the integrand for a three dimensional case for
a full view
reconstruction formula with part of the geometry weights folded into the a(t)
term. Thus, the
transform operator amplifies high frequencies while not eliminating low
frequencies in the
signal. In an embodiment, a(t) = (t+a)2 and b(t) = 1/(t+a), where a is a small
number to prevent
division by zero. In an embodiment, the transform operator may consist of a
sequence of
convolution and signal multiplication operations in (or building upon) the
form described above
to approximate a closed-form inversion or similar equation. In an embodiment,
the transform
operator alone may be applied on the acquired data as a pre-conditioner for a
reconstruction
method or for other processing. In an embodiment, the transform operator is
used as a non-linear
pre-conditioner prior to a sparse or quadratic minimization based
reconstruction algorithm, which
may bring the data closer to the reconstructed form of the solution with the
frequency
components matching the reconstructed geometry for faster convergence.
[00142] In an embodiment, to implement the transform operator formula in
discrete time,
the derivative operation may be replaced with a finite difference operation.
In an embodiment,
the value oft may be replaced with kT, where T is the sample period (inverse
sample rate), and k
ranges from 1 to the number of samples. In an embodiment, the transform
operation is
performed on each channel.
[00143] The following processing steps are an illustrative embodiment of
applying the
transform operator to a set of data such as a sinogram:
a. Create a floating point time values squared array (TV2[]), the array size
being as
large as the number of samples. The elements in the time values squared array
are
populated with the square of kT, where T is the inverse of the sample rate and
k
ranges from 1 to the number of samples (i.e., the first value TV2[0] = T*T,
the
- 38 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
second value is TV2[1] = 2T*2T, etc.). For example, with a sample rate of
100Hz, this array would have [.0001, .0004, .0009, etc.].
b. Create a floating point time values reciprocal array (TVR[]) of the same
size. The
elements of the time values reciprocal array are populated as the reciprocal
of the
corresponding time values array entry (i.e., the first value TVR[0] = 1/T, the
second value TVR[1] = (1/2T), etc.).
c. Create two floating point temporary arrays (T1[] and T2[]) of the same
size.
d. Iterating over each channel:
i. Multiply each sample in the input signal (i.e., channel) by the
corresponding entry in the time values reciprocal array (e.g., T 1 [n] =
Input[n] x TVR[n]; then
ii. Form the finite difference between each multiplied sample and preceding
multiplied sample (e.g., T2[n] = T1[n] - T1[n-1], note, T2[0] may be set to
zero as there is no preceding sample)
iii. Form an output array by multiplying each finite difference by the time
value squared (e.g., Output[n] = T2[n] x TV2[n]
Image Reconstruction (225)
[00144] Above were discussed several optional processing steps for
processing the time
domain optoacoustic return signal. For a variety of reasons, the two
dimensional sinogram data
as discussed herein is not susceptible to closed form reconstruction because,
among other
reasons, complexities involving: tissue attenuation; frequency dependent
tissue attenuation; in-
homogeneities of propagation speed; and in-homogeneities for other tissue
properties. Moreover,
the transducer elements used to acquire the sinogram data are not ideal, i.e.,
perfect, but rather,
have an electro-mechanical frequency response that distorts the data. The
transducer elements
also have directivity and finite-aperture which affects the weighting of the
measured signal
strength corresponding to each pixel, and the transducer array has a limited
view. Further, in
some circumstances, as discussed herein, the acquisition probe uses an
acoustic lens to limit the
opto-acoustic signal of 3D tissue to a 2D imaging plane ¨ suppressing out-of-
plane signals ¨ and
thus, changing the mathematical geometry. The dimensionality of the geometry
represented by
the sinogram data does not conform neatly to a 3D case, a 2D case or a case
with cylindrical
symmetry.
- 39 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00145] Turning now to Figure 4, an illustrative image reconstruction
process is shown,
including several optional steps. Several time-domain processing functions are
discussed as part
of image reconstruction, however, it should be noted that there is no bright-
line distinction to
when preprocessing ends and image reconstruction begins. In other words, one
can consider
preprocessing part of the image reconstruction process. The distinctions made
herein between
preprocessing and image reconstruction are merely for organizational
convenience.
[00146] In an embodiment, raw or preprocessed sinograms may be further
processed in the
time domain, and an image reconstructed there-from. Further processing may,
but need not
include, extract quadrature (405) and sub-band acoustic compensation (345).
Sub-band acoustic
compensation was discussed above, and will not be discussed again in detail ¨
as discussed
above, the pre-reconstruction time domain signal processing order is generally
flexible, and the
various processes may be rearranged for a variety of reasons, including,
without limitation,
optimization, image quality, coding convenience and processing considerations.
Accordingly, in
an exemplary embodiment, the transform operator (350) may be considered, and
included, within
the reconstruction block. The re-ordering of the blocks may, or may not, yield
identical results,
accordingly, in an embodiment, the system described herein may be flexible
enough to permit the
operation of one or more of the blocks in varying sequences.
[00147] In an embodiment, each of the sinograms, e.g., each long and short
sinogram, is
reconstructed. In an embodiment, as discussed in more detail below, the long
and short
sinograms each result in two images, one processed from the real component of
a complex
sinogram, and one from the imaginary component of a complex sinogram. Once
reconstruction
(414), and thus image reconstruction (225), is complete, post-processing,
i.e., image processing
(230), as discussed further below, is performed on the resulting image or
images.
Image Reconstruction (225) - Extract Quadrature (405)
[00148] When measurements are taken with a probe 102, the response of the
transducer
may change the frequency domain phase of the optoacoustic return signal. As an
example, if
there is a shift in phase of a particular frequency component of the
optoacoustic return signal, it
may invert (negative) the corresponding portion of the signal in time domain,
and in effect,
cancel a portion of the signal during a back-projection or other
reconstruction process.
Generally, however, a probe can be calibrated by measuring how it changes the
phase of a signal.
Despite knowledge of how the probe changes the frequency domain phase, the
phase of the
optoacoustic return signal from tissue is unknown, and substantially
unpredictable. The transfer
- 40 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
functions of the acoustic paths between the locations of each acoustic source
and each transducer
element will change under varying mechanical conditions, and upon scanning
different regions or
types of tissue or between subjects. Thus, in this regard, frequency domain
phase cannot be
predicted even where the probe's effect on phase were known precisely. The
frequency domain
amplitude response from each acoustic source in the volume to the transducer
is also an
unknown, however distortions resulting from the miscalibrated frequency domain
amplitude
response of the tissue are of a different nature, and in some cases may not
cause the same degree
of problems, or can be compensated for using other methods. In addition, the
response function is
different for the path from each position in the tissue volume to each
transducer. In all, there
exist a large number of unknown transfer functions for which to compensate.
[00149] Although it is not necessary to rectify the complex-valued
analytic signal prior to
reconstruction, in an embodiment, to counteract the potential unwanted
distortions and
cancellations that may affect the reconstruction process, the sinogram can be
processed into an
analytic representation and stored as complex-valued array. With the negative
frequencies
removed, the complex-valued analytic signal in the time-domain will permit
reconstruction of
images that show instantaneous energy representing the acoustic sources in the
tissue more
accurately. The result of a rectification prior to reconstruction is different
from a post-
reconstruction rectification (i.e., Izil-Hz21+...+IzN1 >= Iz1+z2+...+zNI where
z11 is a complex number
and N is the number of transducers). Said differently, if beamforming (i.e.,
reconstruction) is
performed on band-limited signals without taking the envelope, ringing may
occur in the
reconstructed image. When the complex analytic signal is used for
reconstruction, however, the
same ringing does not occur.
[00150] When the rectification is performed prior to reconstruction, no
destructive
mechanism exists to cancel the signals, which tends to result in high-contrast
but also high
streaking of the image, especially where the view is limited. When the complex
analytic signal is
reconstructed, however, there is a destructive mechanism (which may operate
based on
coherence). Thus, in the formation of any pixel, when the contributing
components of the signals
line up, they will add constructively but when signals are random or
incoherent, which tends to
occur under a variety of circumstances (including when the sources have not
resulted from an
acoustic source associated with the pixel being reconstructed), they will tend
to cancel out. In an
embodiment, this effect may be used to produce higher quality images. In an
embodiment, a real-
valued non-analytic sinogram may also be used to form the image, the envelope
of which may be
-41 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
extracted, if desired, post-reconstruction. In such embodiment, ringing
associated with a real-
valued band-limited or filtered reconstruction may have occurred.
[00151] In an embodiment, an envelope can be extracted from the non-
analytic
reconstructed real image post-reconstruction. The envelope may be extracted by
taking the
envelope of a monogenic representation of the image, which may be carried out
by computing
the Hilbert-transformed directional derivative surfaces of the horizontal and
vertical lines of the
image and then computing for each pixel the square root of the square of the
horizontal
component plus square of the vertical component plus the square of the
original image.
[00152] In an embodiment, an envelope image / auxiliary image can be
formed by
computing the envelope from every vertical line of the image post-
reconstruction.
[00153] In an embodiment, to produce the analytic representation, the
sinogram may be
transformed to the frequency domain, multiplied by a coefficient array where
the negative
frequency components are zeroed and the positive frequency components are
doubled, and then
returned to the time domain, to form the complex-valued analytic
representation. The imaginary
portion of the complex-valued time domain signal represents the "quadrature"
component and the
real portion of the complex-valued time domain signal represents the "in-
phase" component. The
"quadrature" (i.e., imaginary) component, Q, is a function of the "in-phase"
component, I, as
follows: Q = H{I}, where H is the Hilbert transform. In an embodiment, the
Hilbert transform
operator can be used to extract an analytic signal representation from the
real-valued data. In an
embodiment, the Hilbert transform may be performed in the time domain or in
the frequency
domain. Transfer from the time domain to the frequency domain may be done
using a Fourier
transform such as the Fast Fourier Transform, and the return to the time
domain may be
accomplished by an inverse operation such as the Inverse Fast Fourier
Transform.
[00154] In an embodiment, the in-phase and quadrature sinograms can go
through the
reconstruction process separately, each treated as an independent, real-valued
constructions. In
an embodiment, the in-phase and quadrature components can be treated as a
single, complex-
value sinogram, with a single reconstruction stage operating on complex data.
In an
embodiment, weighted delay-and-sum reconstruction (415) may be used to
implement the
reconstruction step. In an embodiment, the output of reconstruction (415) is
treated as complex-
value data, with in-phase and quadrature reconstructed components. In an
embodiment, the
Extract Quadrature (405) step uses as the real component input the (processed
or unprocessed)
sinogram, and returns an imaginary (quadrature) component sinogram having the
same
- 42 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
dimensions as the input sinogram, thus, together with the source sinogram,
forming a complex
sinogram; each of the two sinograms may then be used to form a separate image,
one of the real
sinogram and one of the imaginary (quadrature) sinogram. In an embodiment, the
complex
sinogram may be used to form an image from the complex modulus of each complex
value of the
reconstructed complex image, or, the square root of the real (in-phase) image
component squared
plus the imaginary (quadrature) image component squared.
[00155] In an embodiment, a two dimensional frequency domain transform
comprising a
filtering operation is used to create a secondary image from the complex
image. In an
embodiment the secondary image is created from the complex image using a
convolutional or
FIR filter. As discussed in more detail below, in an embodiment, a series of
processing steps may
be performed on the complex image prior to converting it, or rectifying it, to
a real valued image.
[00156] In an embodiment, the analytic representation of sinogram (with
negative
frequencies removed) may undergo a shift in the frequency domain,
corresponding to complex
demodulation. In an embodiment, such demodulation may be used to further
prevent ringing by
bringing the optoacoustic frequency content remaining after filtering towards
DC. In an
embodiment, such demodulation may be used in conjunction with a bandpass or
smoothing filter
to perform feature size selection, the operation of demodulation assisting in
the display of
features associated with a particular range of frequencies or scale. In an
embodiment, frequency
size selection may be tunable by an operator or selectable from a predefined
list of settings.
Image Reconstruction (225) - Reconstruction (415)
[00157] Reconstruction (415) is a term used to signify the process of
converting the
processed or unprocessed data in the sinogram into an image representing
localized features in a
volume of tissue. In an exemplary embodiment, reconstruction (415) can be
based on a weighted
delay-and-sum approach. As discussed above, the weighted delay-and-sum
algorithm may
optionally be preceded by a transform operator (350). In an embodiment, the
weighted delay-
and-sum algorithm can operate on complex-valued data. In an embodiment,
weights may be
used by reconstruction (415) to represent the contributions from each sample
to be used for each
pixel, and organizationally, the method used to generate the weights may be
considered part of
image reconstruction (225). In an embodiment, the weights may be tuned based
on an analysis of
the collected data.
- 43 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00158] Generally, reconstruction (415) takes as input, processed or
unprocessed channel
data, i.e., a sinogram, and uses this information to produce a two dimensional
image of a
predetermined resolution.
[00159] The dimensions of an individual pixel (in units of length)
determine the image
resolution. If the maximum frequency content in the sinogram data is too high
for the selected
resolution, aliasing can occur during reconstruction. Thus, in an embodiment,
the resolution and
sampling rate may be used to compute limits for the maximum frequency content
that will be
used in reconstruction, and thus to avoid frequency content that is too high
for the selected
resolution. In an embodiment, the sinogram can be low-pass filtered to an
appropriate cutoff
frequency to prevent the aliasing from occurring.
[00160] Conversely, if the sampling rate is too low to support the image
resolution, then,
in an embodiment, the sinogram can be upsampled and interpolated so to produce
a higher
quality images. While the two dimensional image can be any resolution, in an
exemplary
embodiment, the image can comprise 512x512 pixels. In an another exemplary
embodiment, the
image can comprise 1280x720 pixels. In yet another exemplary embodiment, the
image may
comprise 1920x1200 pixels. In an embodiment, the horizontal resolution is at
least 512 pixels
wide, but not more than 2560 pixels wide, and the vertical resolution is at
least 512 pixels high,
but not more than 1600 pixels high.
[00161] A two dimensional image may represent variations in the volume,
such as
structures, blood, or other inhomogeneities in tissue. The reconstruction may
be based upon the
first propagation time from each location in the tissue to each transducer and
the contribution
strength of each sample to each pixel. The signal intensities contributing to
each pixel in the
image are combined to generate the reconstruction.
[00162] The following processing steps are an illustrative embodiment of a
reconstruction
algorithm using a weighted delay-and-sum technique:
a. Allocate an output image array and set all values to zero
b. For each transducer channel:
i. For each pixel in the output image array:
1. Access the delay (in samples) from Sample Delay Table for that
channel and pixel, and then retrieve the sample (from the
sinogram) corresponding to the channel and delay
- 44 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
2. Access the weight from Weights Table corresponding to the
channel and pixel
3. Multiply the sample by the corresponding weight
4. Add and store the result with in location of the output image array
corresponding to the destination pixel.
[00163] The weights table is a table representing the relative
contribution of each sample
in the sinogram to each pixel in the resulting image. In an exemplary
embodiment, for relative
computational efficiency, the same weights table can be used for the real and
imaginary
components of a complex sinogram. In an embodiment, separate weights table can
be used for
each of the components of a complex sinogram. In an embodiment, one complex
weights table
can be used for the real and imaginary components of a complex sinogram. In an
embodiment,
separate complex weights table can be used for each of the components of a
complex sinogram.
In an embodiment, a complex weights table can be used to account for standing-
wave type
patterns in the image that are the result of the system geometry.
[00164] The weights table can be used to establish something akin to an
aperture in
software. Thus, in an embodiment, where a wider aperture is desired, more
weight is given to
off-center samples. Stated in other words, for example, for a given
transducer, usually no sample
would be given more weight than the sample directly beneath the transducer,
and for the
purposes of illustration, consider that the weight for a given sample directly
beneath the
transducer is 1. Consider further the relative contribution of samples that
are at 15, 30 and 45
degrees from center, but equidistant from the transducer. To narrow the
aperture, those samples
could be weighted 0.5, 0.25 and 0.12 respectively, while to widen the
aperture, those same
samples could be weighted 0.9, 0.8 and 0.7 respectively. The former would
provide only a slight
(12%) weight to samples received from a source at 45 degrees from center,
while the latter would
provide the same sample much higher (70%) weighting. In an embodiment, the
system
displaying the optoacoustic output ¨ which may, but need not be the same as
the system
acquiring the sinogram ¨ would provide the operator the ability to vary this
parameter (i.e., the
software aperture) when viewing optoacoustic images.
[00165] In an embodiment, a very large table contains a mapping of
relative weight and
delay for each pixel and transducer. Thus, in an embodiment where a target
image is 512x512
pixels and the probe 102 has 128 channels (i.e., transducers), there are
33,554,432 weight entries
and the same number of delay entries. Similarly, in an embodiment where a
target image is
- 45 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
1280x720 pixels and the probe 102 has 128 channels (i.e., transducers), there
are 117,964,800 of
each type of entry. In an embodiment where a target image is 1920x1200, and
the probe has 256
channels, there are almost 600 million entry of each type.
[00166] As discussed above, the extract quadrature step (405) provides an
imaginary
component sinogram, and in an embodiment, each of the real and the imaginary
component
sinograms may be reconstructed into an image, thus producing two images, one
for each
component of the complex sinogram. In an embodiment, delay and weight tables
are the same
for each component of the complex sinogram. In an embodiment, the delay table
is the same for
each component of the complex sinogram, but the weight table is different for
the real and
imaginary component sinograms. In an embodiment, the weight table is the same
for each
component of the complex sinogram, but the delay table is different for the
real and imaginary
component sinograms.
Image Reconstruction (225) - Calculate Weights and Delays
[00167] As discussed above, in the illustrative embodiment of a delay-and-
sum
reconstruction algorithm, a Weights Table may be employed. An algorithm may be
used to
calculate the Sample Delay Table and Weights Table for each transducer. In an
embodiment, the
data comprising Sample Delay Table(s) correlates the estimated contribution of
each transducer
to each pixel, while the data comprising the Weight Table(s) provides an
estimate of the relative
weighting of the contribution of each transducer to each pixel as compared to
the other
contributions to that pixel. In an embodiment, the Weights Table may be used
to account for
angular apodization with respect to the transducer's norm, power of the laser,
time gain control,
light attenuation within the tissue, skin thickness, coupling medium
characteristics, patient
specific variables, wavelength specific variables and other factors.
[00168] In an embodiment, each of the tables corresponds in size (in
pixels) to the two
dimensional image output by image reconstruction, and a plurality of each
table are created, one
for each channel. In the illustrative embodiment above, each Sample Delay
Table correlates the
pixels of the target image with the samples in an sinogram, thus, one Sample
Delay Table (which
is specific to a channel) will identify for each pixel in the image, the
specific sample number in
that channel that is to be used in calculating that pixel. Similarly, in the
illustrative embodiment
above, each Weights Table correlates the pixels of the target image with the
weight given to the
sample that will be used; thus, one Weights Table (which is specific to a
channel) will identify
- 46 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
for each pixel in the image, the weight to be given to the sample from that
channel when
calculating the pixel.
[00169] X- and Y- coordinates of the image pixels are calculated using the
input
information on the image size and location. The time delays are calculated for
each transducer
and each pixel by knowing the distance between pixel and transducer and the
speed of sound. If
an acoustic matching layer with different speed of sound is used, then
separate time delays are
calculated inside and outside of the matching layer and added together,
resulting in the overall
transducer-pixel delay. The weights are calculated for each transducer and
each pixel, depending
on their relative location. The distance and angle between the transducer-
pixel vector and
transducer's norm are taken into account, as well as the depth position of an
individual pixel. In
an embodiment, the system calculating the weights and/or delays ¨ which may,
but need not be
the same as the system acquiring the sinogram or displaying the images
reconstructed there-from
¨ would provide the operator the ability to vary parameters used in
processing. In an
embodiment, the system calculating the weights would provide the operator the
ability to vary
the bases for the weight calculation, thus, e.g., giving more or less weight
to off-center acoustic
data. In an embodiment, the system calculating the weights would provide the
operator the
ability to controls whether linear or power relationships are be used in
calculation of the weights.
[00170] Pseudo-code in the Appendix will provide a guide for a person of
ordinary skill in
the art in implementing an illustrative algorithm to calculate weights and
delays.
[00171] Once reconstruction (414), and thus image reconstruction (225), is
complete, post-
processing, i.e., image processing (230), may be performed on the resulting
image or images.
[00172] In an embodiment, image reconstruction may be based on Adaptive
Beamforming,
Generalized Sideband Cancellation, or other methods as are known in the art.
In an embodiment,
techniques for reconstruction may be based on determining cross-correlations
functions between
channels and/or maximizing the sharpness objective of the image.
[00173] In an embodiment, a method to reconstruct a volume may consist of
decomposing
a cross-section or volume into radial wavelets, the radial wavelets
representing optoacoustic
sources (the measured optoacoustic return signal of radial optoacoustic
sources in particular are
presumed to obey a simple closed form equation), the technique of Wavelet-
Vaguelette
decomposition may be used to relate the wavelets and vaguelettes between the
image domain and
the sinogram and to thereby determine the intensities of the radial wavelets
in the image, and thus
to reconstruct the image. In an embodiment, the projection of radial wavelets
from the image
-47 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
domain into the sinogram domain (i.e., vaguelettes) can be used in conjunction
with other image
formation techniques prior to determining the intensities of the of the radial
wavelets. In an
embodiment, adaptive beamforming, or wavelet de-noising involving thresholding
can be
performed on the radial-wavelet projections as a stage such a reconstruction.
[00174] In an embodiment, reconstruction may be based on Iterative
Minimization or
Iterative Maximization, such as, for example, Li-minimization or L2-
minimization. Iterative
Minimization algorithms for reconstruction and enhancement require high
computational load
and thus, are not considered applicable for real-time imaging. Real-time
optoacoustic
reconstruction of a cross-section of a volume can be performed using an Li-
minimization
algorithm. In an exemplary embodiment for performing Li-minimization
reconstruction in real-
time on a 2D cross-section of a volume, the Fast Wavelet Iterative
Thresholding Algorithm is
used, and combined with the Helmholtz wave equation in the frequency-domain,
which can be
efficiently used to represent optoacoustic wave propagation yielding a
diagonalizable (or nearly
diagonalizable) system matrix. In an embodiment, the pixels of the image may
be decomposed
into radial wavelets, the decomposition represented in the frequency domain as
radial subbands,
and the radial subbands used in the iterative thresholding. In an embodiment,
the Fast Wavelet
Iterative Thresholding Algorithm may be used where the system matrix is found
empirically
rather than through using an ideal equation.
[00175] When the laser illuminates the volume of tissue with at least a
portion of the
surface being adjacent to a medium that is not perfectly matched to the
acoustic properties of the
volume, the propagating acoustic wave may reflect ¨ at least in part ¨ off the
unmatched surface
and propagate into the volume as an incident wave-front. The incident wave-
front can further
reflect off acoustic discontinuities in the tissue and interfere with the
optoacoustic return signal
creating an artifact. This artifact can be separated from the optoacoustic
return signal using, e.g.,
an interactive minimization technique. In an embodiment, an image mapping the
intensity of this
artifact can be produced.
[00176] In an embodiment, a pattern detection classifier can be applied to
an optoacoustic
return signal, wherein the classifier output reflects the strength of a
particular indicator as a
function of time (or distance). Accordingly, upon obtaining measurements from
multiple
transducer positions, the classifier output can be beam-formed to localize the
source (i.e.,
phenomenon) causing the pattern detected. An image produced from the beam-
formed classifier
output may suffer from blurring, reconstruction artifacts, and streak
artifacts, which may be
-48-
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
particularly acute in a limited-view case. These artifacts may result at least
in part because the
pattern classified signal may lack information concerning signal strength that
is part of a non-
pattern classified sinogram, and its intensity is related to the presence of
the pattern, not
necessarily on the distance that the transducer is located from the source of
the pattern. The
classifier output of a classified optoacoustic signal, however, can be "fit"
into the propagation
model of the Helmholtz equation where the classifier output is characterized
as originating from
an instantaneous source term at a given position. Thus, to reduce the
streaking, blurring and
artifacts a parametric map of the pattern classified signal can be formed
using techniques for
reconstruction and deconvolution other than simple beamforming. Application
of, e.g., an
iterative minimization technique can be used to reduce streaking and thus
better localize the
source of the pattern. Different types of classifiers and reconstruction
techniques may have
different considerations that apply. In an exemplary embodiment, a parametric
map of the
classified quantity can be produced by using an iterative minimization
technique, where the
system matrix is formed as it would be had the source been an optoacoustic
signal. In an
embodiment, the sparse basis representation used by, e.g., Li minimization,
may serve to localize
the source of the pattern and hence reduce artifacts. Thus, rather than
applying the reconstruction
technique to an optoacoustic return signal, it may be applied to classifier
output, where the
classifier output is represented in the form of a sinogram. In an embodiment,
the reconstruction
technique is applied as though the classifier output were an optoacoustic
return signal. In an
embodiment, further processing, such as taking a complex envelope of the
classifier output,
filtering, or deconvolving the classifier output may be performed prior to
reconstruction. In an
embodiment, the classifier may be designed to discriminate between normal and
abnormal
branching blood vessels in tissue.
Image Processing (230)
[00177] As discussed above, after the long and short sinogram are acquired
(205, 210),
optionally preprocessed (220) and then image reconstructed (225) to form
images, certain post
processing may be performed on the resulting images. Turning now to Figure 5,
optional post-
processing steps are shown, including remove inter-frame persistent artifact
(505), fluence
compensation (510) and complex magnitude (515). In an embodiment, image
processing
produces an envelope image (520) that is positive real valued (not complex-
valued).
- 49 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Image Processing (225) - Remove Inter-frame Persistent Artifact (505)
[00178] The optoacoustic return signal comprises both desirable and
undesirable
information, among the information that may be undesirable is what will be
referred to herein as
the undesired coupled response. The undesired coupled response may include
artifacts that result
from light striking a person's skin as it penetrates into the tissue. More
generally, the undesired
coupled response being addressed by this step is inter-frame persistent signal
or inter-frame
persistent artifact. Inter-frame persistent signal, as used herein, refers to
an interfering signal that
remains constant, or changes very slowly, and which is therefore presumed to
produce similar
interference in each of a plurality of images that are spatially and/or
temporally related. Inter-
frame persistent artifact refers to the same phenomenon , but when it appears
in a reconstructed
image. Thus, the terms inter-frame persistent signal and inter-frame
persistent artifact may
sometimes be interchanged herein because they represent the same phenomenon.
The problem of
removing inter-frame persistent signal is complicated by the fact that the
similar interference
found in separate frames may be scaled in amplitude by a constant factor. The
scaling may be
related to a number of factors, including, without limitation variation in the
total light energy
used to cause the optoacoustic return signal. Moreover, generally, inter-frame
persistent signal
varies sufficiently from person to person, that it is not readily identifiable
except by examination
of a plurality of frames for a given individual. In an embodiment, a plurality
of frames taken in
relatively close spatial and/or temporal proximity to each other, but
generally not in an identical
location, are analyzed with the goal of removing inter-frame persistent
signal.
[00179] In an embodiment, in a first process directed to the removal of
inter-frame
persistent signal, a step is performed to estimate its composition. In an
embodiment, an inter-
frame persistent signal is taken as the first principal component from a set
of independent frames.
The first principal component can be computed using any method, although, in
an embodiment,
the first principal component can be computed using SVD (singular value
decomposition) or an
equivalent iterative method.
[00180] In an exemplary embodiment, the set of independent frames is
selected such that
each frame has independent background noise. In other words, generally,
independent frames
taken when the probe 102 is not moving should not be included in the set.
Accordingly, in an
embodiment, each sequential frame that may be considered for use in the set
may be flagged to
indicate its suitability (or to indicate its non-suitability) for inclusion in
the set. To analyze a
frame for suitability or non-suitability for inclusion in the set, the frame
may be compared to one
- 50 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
or more frames preceding it in sequence. The flagging of a frame (as suitable
or non-suitable)
may be done at capture-time, or thereafter, but prior to the step estimating
the inter-frame
persistent signals. In an embodiment, the flagging of a frame (as suitable or
non-suitable) is
performed prior to writing that frame to the LOM file. In an embodiment, the
process of
estimating the inter-frame persistent signals may include a frames selection
sub-step.
[00181] The following processing steps are an illustrative embodiment of
an inter-frame
persistent signal estimator:
a. Initialization (enter if sizeOfFrameBuffer has changed, or Nr (number of
rows in
frame) or Nc (number of columns in frame) has changed)
i. For each channel, allocate a frameBuffer as a circular buffer to have
sizeOfFrameBuffer frames.
ii. Set frameBuffer.start[channel] to 0 and frameBuffer.end[channel] to 0 for
each channel. These two variables keep track of the active frames in the
circular buffer.
iii. For each channel allocate estimate[channel][Nr][Nc] and set all elements
to O.
b. If captureFrame is true (thus the frame is flagged as suitable for
inclusion in the
set) then
i. Optionally, apply an image transform to frame in (e.g., a two dimensional
wavelet transform, a two dimensional FFT, or another similar transform; a
band pass filter may be applied to remove certain frequencies from the
computation)
ii. Add frame in to the frameBuffer for the current channel. If the buffer is
full overwrite the oldest frame in the buffer.
c. If computeFrame is true then
i. Map all of the data in frameBuffer into a matrix where each frame in the
buffer is treated as a column and each row is a value of the same pixel
index.
ii. Compute the principal component (or independent components) of
frameBuffer for the current channel.
iii. (If an image transform was applied to frame in, apply the inverse
transform to the results of the previous calculation.
-51 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
d. Output estimate out for the current channel as the selected principal
component
(or independent component), absent an alternative selection, the first
principal
component is selected.
[00182] In connection with the foregoing process steps it should be noted
that for
optimization of step c(ii), computation of the full SVD may not be real-time.
It is not necessary
that the persistent frame estimation process run on every frame. In an
embodiment, the persistent
frame estimation process may be re-updated periodically, e.g., based on a
trigger external to the
algorithm. In an embodiment, it may be beneficial to run persistent frame
estimation process in a
thread and utilize the most recently finished estimate only. In an embodiment,
the first principal
component is found in the complex domain, thus, the SVD (or other) function
should accept
complex-valued input. In an embodiment, the inter-frame persistent signal
estimate should have a
zero mean, and unit L2-norm. In an embodiment, only the first principal
component is
computed. In an exemplary embodiment, the first principal component is
computed for the
estimate on the complex image using a power iterative method for efficiency.
In an embodiment,
the interframe persistent signal estimate is the first several principal
components. In an
embodiment, the interframe persistent signal estimate is the first several
independent
components. In an embodiment, when multiple estimates are generated, each is
removed from
the signal. In an embodiment, the inter-frame persistent estimate can be
performed in an image
transform domain, such as a two dimensional wavelet transform domain or two
dimensional FFT
transform domain, as discussed above. In an embodiment, the inter-frame
persistent estimate can
be performed on a band-passed set of data.
[00183] Once the inter-frame persistent signal is estimated, it can be
removed from the
frames. In an embodiment, the inter-frame persistent signal may be subtracted
from the frame.
As discussed above, although the interference may be identical from frame to
frame, it may be
scaled in amplitude. Thus, in an embodiment, prior to subtraction of the inter-
frame persistent
signal estimate from the source frame, a scaling factor should be computed,
and the scaling factor
may be used to scale the estimate so that it can be subtracted from the source
frame. The scaling
factor is the projection of the inter-frame persistent signal component. In an
embodiment,
multiple inter-frame persistent signals may be estimated. In an embodiment
each of the multiple
inter-frame persistent signals may correspond to the highest energy components
in the
decomposition method used to perform the computation (e.g., first 3 SVD
components).
- 52 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Image Processing (230) - Fluence Compensation (510)
[00184] Because skin and tissue characteristics vary from patient to
patient, light
distribution in the tissue of a specific patient cannot be predicted. The
fluence profile of the light
can be broken down into a spatially-dependent common light penetration profile
component and
two spatially-dependent wavelength-specific fluence-ratio profiles, which
relate the true fluence
to the common light penetration profile. In an embodiment, the common light
penetration profile
and wavelength-specific fluence-ratios may be used to compensate for patient
specific variations
that affect the distribution of light within the tissue. In an embodiment, 1-
dimensional curves
based on a model of fluence behavior for the common profile and specific
profile may be used,
with a single patient specific parameter, to generate the two dimensional
fluence compensation
curves. In an embodiment, any of the following equations may be used without
limitation as for
compensation curves:
Type Equation
LINEAR f(x,g) = 1 + g * x
EXPONENTIAL f(x,g) = exp(g * x)
EXPONENTIAL DIV f(x,g) = x * exp( g * x)
IDENTITY f(x,g) = 1
[00185] Other equations or simulated curves may be used for the
compensation curves. In
an embodiment, experimentally measured fluence distribution curves can be used
as a method of
compensation. In an embodiment, a separate device or a separate sensor (that
may use
optoacoustic principles) can be employed to measure the fluence curves in real-
time during the
light event. In an embodiment, the fluence compensation curves can be derived
(i.e., estimated)
from simulations. In an embodiment, the reciprocal (or modified reciprocal) of
a measured or
simulated curve may be used as a one dimensional fluence compensation curve.
In embodiment,
a measured or simulated curve may be filtered prior to being used in fluence
compensation. In an
embodiment, fluence compensation curves based on statistical features may be
computed as a
function of depth in a single image or in a set of images dynamically
acquired.
[00186] Turning now to Figure 6, a set of process steps for fluence
compensation (510) is
shown. In an embodiment, the system performing processing on the optoacoustic
data, and/or
the system displaying the optoacoustic output ¨ which may, but need not be the
same as the
system acquiring the sinogram ¨ would provide the operator the ability to
select between
available equations, and select a parameter used for processing an
optoacoustic image or its
derivative for viewing. Thus, in an embodiment, an operator may select a
curve, such as the
- 53 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
exponential curve, and/or a parameter, such as the exponent. In an embodiment,
the curve, and
possibly the parameter, are selected from a finite list of selections
presented to the operator in a
user interface. Once the curve and parameter are selected, the common fluence
curve (605) and
wavelength specific curves (610) are calculated. Thereafter, in an embodiment,
a two
dimensional (e.g., a curve for each pixel column) overall fluence
normalization curve (615) is
computed. The two dimensional overall fluence normalization curve is then
applied to the image
(620). In an embodiment, the compensation curves are automatically selected
from a set of
compensation curves based on image statistics or statistics of a region of
interest within the
reconstructed image. In an embodiment, the fluence compensation curve may be
computed
based on a region-of-interest identified in real-time by a system operator,
the fluence
compensation curve being dependent on a measure of depth of the identified
region-of-interest.
In an embodiment, a region-of-interest may be identified by selecting a
rectangular region-of-
interest of a target object, the center of the region corresponding to the
depth used to determine
the compensation curve.
[00187] The following processing steps are an illustrative embodiment of
producing a two
dimensional fluence compensation curve from a selected one dimensional
equation applicable for
an ideal linear array and applying it to an uncompensated image:
a. Compute one dimensional array containing the depths for each pixel in the
image
starting at the minimum image depth until the maximum image depth. Store the
result in the vector "x".
b. Calculate one dimensional common fluence compensation curve based on the
common gain parameter "go" using a selected compensation function for fo(x,go)
for the fluence compensation.
c. Calculate one dimensional channel-specific compensation curves for each
channel
i. The channel 1 curve is based gain parameter "gi" using a selected
compensation function for fi(x,gi) for the fluence compensation.
ii. The channel 2 curve is based gain parameter "g2" using a selected
compensation function for f2(x,g2) for the fluence compensation.
d. Calculate the overall two dimensional normalization curves from the one
dimensional common curve and channel specific curve.
i. For each channel, create an overall one dimensional curve by multiplying
the common curve with the channel specific curve
- 54 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
ii. Set each vertical column in the two dimensional normalization curve equal
to overall one dimensional curve
e. For the current channel reconstructed image
i. for each pixel in the image, multiply the value of the pixel by the
corresponding pixel in overall two dimensional normalization curve
belonging to the current channel
[00188] In an embodiment, Fluence Compensation (510) may process the
complex image,
and provides a new complex image as its output. In an embodiment, Fluence
Compensation
(510) may process a real image, and provides a modified real image as its
output.
Image Processing (230) - Complex Magnitude (515)
[00189] In an embodiment, the complex magnitude (515) step takes as input
the complex
image (or a real image where the imaginary component is not available), and
produces an
envelope image that has the same number of rows and columns as the input
image. The envelope
image may be determined by taking the complex magnitude of each element of the
input. Where
the real image alone is available, the envelope image is the absolute value of
the information in
that image. In an embodiment, the envelope can be computed alternately from
the real image
alone by producing an image in substitute for the imaginary component image
where each
vertical line in the imaginary image is the Hilbert transform of the
corresponding line in the real
image; the complex magnitude being applied in the same way.
Generate Parametric Images (240)
[00190] As discussed above, after the long and short sinogram are acquired
(steps 205,
210), optionally preprocessed (step 220) reconstructed (step 225) to form
images, and processed
(step 230) to produce short (232) and long (234) envelope images, the envelope
images are used
to generate parametric images (step 240), and more specifically, to generate
one or more of the
following parametric images: an oxygenation map (250), a hemoglobin map (255)
and a masked
oxygenation map (260). In an embodiment, parametric images are presented by
providing a
colorized image reflective of qualitative information obtained from within the
short and long
envelope images (232, 234).
[00191] Turning now to Figure 7, the short envelope image (232) and long
envelope image
(234) are processed to provide at least one of the parametric images (250,
255, 260). In an
embodiment, the short envelope image (232) and long envelope image (234) may
be processed
- 55 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
by motion and tracking (705) to improve the signal to noise ratio and/or
provide better alignment
between the images. In an embodiment, the short envelope image (232) and long
envelope
image (234) are processed by oxygenation and hemoglobin calculation (720) to
produce
grayscale maps of oxygenation and hemoglobin. More generally, a plurality of
parametric maps
(i.e., two or more) may each be formed from the information in a plurality of
images (i.e., two or
more), and another parametric map may be formed from the information in at
least two of the
plurality of parametric maps. It is within the scope of this disclosure that,
rather than forming
another parametric map from the information in at least two of the plurality
of parametric images,
such latter parametric map may be created directly from the information in the
plurality of
images. In other words, in cases where mathematics does not require the
creation of the
intermediate parametric maps, should the only reason to do so be to combine
them into the latter
combined parametric map, the separate step of producing the intermediate maps
may, in an
embodiment, be omitted.
[00192] Once created, parametric maps may be denoised (735). In an
embodiment the
grayscale maps are statistically color mapped to produce color maps of
oxygenation (250) and
hemoglobin (255). The hemoglobin map (255) may thereafter be in combination
with the
oxygenation map (250) to provide a masked oxygenation map (260) in the combine
transparency
mask (750). In an embodiment, the result of Generate Parametric Images (240)
is an RGBA
oxygenation map an RGBA hemoglobin map and an RGBA Hg0 masked oxygenation map.
As
discussed above, in an embodiment, the color mapped quantity similar to the
masked
oxygenation map may be generated directly from the data in the two envelope
images, rather than
passing through the intermediate stage of combining the transparency channels
of the
oxygenation map and hemoglobin map.
Generate Parametric Images (240) - Motion and Tracking (705)
[00193] Motion and tracking (705) may be necessary because, as successive
images of a
static (or slow moving) scene are generated, motion in the sensor will cause
the position of
content of the scene to "move" relative to each other. Thus, a subsequent
image, gb, taken a short
time (e.g., 100 ms) after a previous image, ga, may be offset by a number of
image pixels in the
horizontal and vertical dimension from the previous image, ga. Similarly,
subsequent images
may also be subject to non-rigid deformations that can occur between frames.
In an embodiment,
corrections may be made for non-rigid deformations. Moreover, in an
embodiment, further
motion and tracking may be employed to determine how the probe is moving, thus
providing a
- 56 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
basis to generate a 3D image of the tissue structures. In an embodiment, and
as discussed in
more detail below, the system may include sensors (e.g., accelerometers, or
fixed positions
sensors and targets, or otherwise) that will provide data concerning the
position or movement of
the probe during imaging. Such information concerning position or movement may
be taken into
account in making correction for translation, rotation, angular deflection, or
other probe
movement that may cause deformations from frame to frame.
[00194] Turning briefly to Figure 8, in an embodiment, the step of motion
and tracking
(705) is broken out into component parts, which may include motion estimation
(810),
persistence (820) and alignment (830). In an embodiment, the motion estimation
(810) process
may be used to estimate motion between two images. In an embodiment, the rigid
motion
between the images is assumed to have no rotational component of motion. In an
embodiment,
the rigid motion between the images may be assumed to have a rotational
component of motion.
In an embodiment, the persistence (820) process may be used to improve the
signal to noise ratio.
In an embodiment, the alignment (830) process aligns two images, such as a
short envelope
image (232) and a long envelope image (234).
[00195] Motion estimation (810) can provide information that may support
one or more
methods of removing the effect of probe motion between successive image
acquisitions. In an
illustrative embodiment, motion estimation (810) estimates motion that
occurred between a short
envelope image (232) and a long envelope image (234). In an embodiment, the
motion
estimation (801) process requires input of the number of rows and columns in
the image, as well
as cutoff values for a raised cosine apodized bandpass filter. In an
embodiment, a filter array is
created on startup, or whenever there is a change to the input parameters. The
filter array may be
created by determining the 2D frequency components, and then using a raised
cosine apodization
function to smoothly shape the bandpass characteristics of the filter and/or o
that the bandpass
range corresponds to frequencies relevant to features that are tracking. In an
embodiment, using
a raised cosine apodization function creates a radial 2D bandpass filter in
the frequency domain
to suppress components that are less likely to correlate in the motion
estimation procedure, which
may depend on the specific nature of optoacoustic scans. A correlation array
computed using a
buffered image and another image may then be determined, and correlation
determined there-
from. In an embodiment, a phase correlation algorithm may provide a frequency
domain
approach to estimate the relative positions of the content of two images. In
an embodiment,
given two input images, ga. and gb, taken a short time apart, and where Ga. =
F {g}, and Gb =
- 57 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
F {gb}, and where F {g} = 2D Fourier Transform if image g, the cross-power
spectrum of the
phase, R can be formed as follows:
r
"
=
161, 67; I
a normalized cross-correlation, r, can be provided by using the inverse
Fourier Transform:
r = fR)
and the offset, in pixels, is equal to the location of the peak in r:
= arg M a tri
In an embodiment, filtering (2-D) or zero padding in the edges may be applied
to the images
(before the Fourier transform) to compensate for edge effects. In an
embodiment, a small
constant may be added to the denominator of the cross-power spectrum term R,
to serve as a
filter for weak values, and/or to prevent division by zero. In an embodiment a
bandpass filter
(i.e. the 2D radial raised-cosine apodized frequency domain bandpass filter
described above) may
be multiplied with the numerator of the cross-power spectrum.
[00196] In an embodiment, the motion is expressed in horizontal and
vertical pixels, and
may be provided along with additional correlation values. The correlation
values may be
expressed in a variety of ways, and in an embodiment, is expressed by
providing a mean value of
the absolute value of the cross correlation array along with the maximum value
of the absolute
value of the cross correlation array. In an embodiment, the pixel motion
between successive
frames, by knowing the timing of when frames are collected, may be used to
estimate the
velocity of the motion along an axis. In an embodiment, the estimated velocity
of the motion may
be filtered to remove error, to produce a filtered estimate of velocity. In an
embodiment, the
estimates of velocity may be used to estimate the position of the probe at a
given time. In an
embodiment, the estimate of the position of the probe at a given time may be
used in co-
registration with ultrasound, such that during co-registration, the position
of the optoacoustic
parametric map or opto-acoustic image is shifted to correspond with the
anticipated position for
the overlay based upon the known time at which the ultrasound frame gets
collected;
accordingly, when ultrasound and optoacoustic information is collected in an
interleaved fashion,
a smoothly tracking motion of the co-registered overlay can be produced, that
can also reduce
positional misalignment between co-registered frames.
[00197] The following processing steps are an illustrative embodiment of
motion
estimation:
a. Create (or recreate) a filter array based on the input parameters,
by:
i. Getting the radial frequency components,
- 58 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
ii. Using a raised cosine apodization function to create a bandpass filter
array;
b. Determine the correlation between the previous frame (stored in prior
iteration of
algorithm) and the current frame, and calculate the translation offset vector;
c. If the value of the correlation is lower than a threshold, and the
translation is also
lower than a threshold, the motion can be assumed perpendicular to the imaging
plane;
d. Store the current frame as the "previous" frame;
e. The probe velocity may be estimated from the translation using the time
elapsed
between the frames;
f. In an embodiment, the translation or velocity outputs may be low pass
filtered to
have a smoother estimate of velocity.
[00198] In an embodiment, once motion is estimated, a persistence (820)
process may be
run to filter out noise and strengthen the true signal in the image. The
persistence (820) process
presumes that unwanted signal, e.g., noise, may be present in the image, than
the unwanted signal
will change from frame to frame. In an embodiment, the unwanted signal may be
modeled as
Gaussian white noise. In an embodiment, it is assumed that the two images upon
which the
persistence (820) process is run will be highly correlated, making the change
in true image
content from frame to frame small. It will be apparent to a person of skill in
the art that the lower
the change in true image content, the better the results that will be
achieved.
[00199] In an embodiment, the persistence (820) process performs a
weighted moving
averaging (WMA) on image data, where one or more previous frames are weighted
and
considered with the image. In an embodiment, the weight given to previous
frame or frames may
depend on a single input parameter. In an embodiment, the weight given to
previous frames may
depend on a plurality of parameters. In an embodiment, the persistence (820)
process performs
exponentially weighted moving averaging (EWMA) on image data, which is a type
of (infinite
impulse response) IIR filter. Using an IIR filter, instead of a finite impulse
response (FIR) filter
permits storing less data in memory for calculation, such as, for example,
having only an array of
the image, and an array for previous frames in memory.
[00200] In an embodiment, for a sample, n, the output value, y[n] is
calculated from an
input value x[n] and the previous output value y[n- 1 ] as y[n] = (1-a) x[n] +
a y[n-1]. If n < 0 then
y[n] = 0.
[00201] The following processing steps are an illustrative embodiment of
persistence:
- 59 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
a. During initialization or if the image size has changed
Allocate and initialize an array called persistence buffer
b. If translational motion has been detected (and the buffer is not being
flushed)
i. shift the persistence buffer for the current channel using linear
translation
the detected amount
c. For each pixel in the input image
i. If the persistence buffer is not being flushed, then
persistence buffer[channel][pixel] = (1-alpha)*input image[pixel] +
alpha*persistence buffer [channel] [pixel];
else
flush the persistence buffer for the channel by setting the value of the
input image pixel e.g., persistence buffer [channel] [pixel] =
input image [pixel];
ii. output image[pixel] = persistence buffer[channel][pixel]
[00202] In an embodiment, once the persistence (820) process is run, an
alignment (830)
process may be used to align the present image and the prior one. In an
embodiment, the
alignment (830) process may rely upon the results (e.g., horizontal and
vertical pixel
calculations) of motion estimation (810). In an embodiment, the alignment
(830) process may
estimate the movement between the previous frame and the frame under
consideration. The
alignment (830) process provides an output image shifted by a vertical and/or
horizontal offset.
In an embodiment, the vertical and/or horizontal offset is provided in pixels.
In an embodiment,
the motion estimate for the persistence process uses phase correlation
information from the
images of similar wavelength channels, since images from similar channels will
have the most
similar features for performing motion estimation. In an embodiment, the
alignment process runs
on images of dissimilar wavelength channels since the images from dissimilar
channels should be
aligned prior to calculation.
[00203] In an embodiment, the motion estimate and correlation are used to
automatically
detect frames used by the interframe persistent artifact estimation procedure.
Generate Parametric Images (240) - Oxygenation and Hemoglobin Calculation
(720)
[00204] After motion and tracking (705) an aligned short envelope image
(710) and an
aligned long envelope image (715) can be processed using oxygenation and
hemoglobin
calculation (720) to produce a grayscale oxygenation map (725) and a grayscale
hemoglobin map
- 60 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
(730). Generally, optical absorption in blood is different at differing
wavelengths of light.
Moreover, optical absorption in blood is affected by blood oxygenation.
Because of the
coefficient of absorption, at some wavelengths of light, blood of a given
oxygenation is more
optoacoustically responsive than blood at a lower oxygenation, while at other
wavelengths of
light, the reverse is true. For example, oxygenated blood is less
optoacoustically responsive than
deoxygenated blood in response to stimulus from an Alexandrite laser, which
has predominant
output at about a 757 nm wavelength, while blood oxygenated blood is more
optoacoustically
responsive than deoxygenated blood in response to stimulus from an Nd:YAG
laser, which has
predominant output at about a 1,064 nm wavelength.
[00205] Turning to Figure 9, and as discussed in more detail below, a
hemoglobin map and
an oxygenation may be computed using information about the absorption
coefficients for deoxy-
hemoglobin and oxy-hemoglobin at the short and long wavelengths. Because the
penetration of
light into tissue can vary, in an embodiment, the light penetration may be
statistically normalized
(normalize fluence (910)), In an embodiment, light penetration may be
statistically normalized
within a region of interest (ROI). In an embodiment, smoothing (920) may be
applied. In
addition, in an embodiment, oxygenation calculation (940) (but not hemoglobin
calculation
(950)) may be enhanced by a noise removal (930) process. In an embodiment,
either hemoglobin
and/or oxygenation calculations may be enhanced by a noise removal process
[00206] In an embodiment, the system performing processing on the
optoacoustic data,
and/or the system displaying the optoacoustic output ¨ which may, but need not
be the same as
the system acquiring the sinogram ¨ would provide the operator the ability to
select a region of
interest. In an embodiment, a graphical user interface would permit the user
to identify a region
of interest within, e.g., an ultrasound or optoacoustic image. In an
embodiment, the ROI is a
rectangular region. In an embodiment, the ROI may be non-rectangular. In an
embodiment, the
ROI is specified by a value, e.g., a Boolean value, for each pixel in the
image and/or in the
resulting parametric map to indicate if that pixel is part of the
computational region of interest; in
this way, the calculation is not limited to performing on rectangular shapes.
In an embodiment, a
separate ROI may be used for display purposes, thus, for example, one ROI may
be used
computationally, and a separate ROI may be used as a boundary display in the
displayed image.
In other words, the computational ROI and the display ROI need to be the same
ROI.
[00207] In an embodiment, the fluence in the ROI within the short envelope
image (232)
and the long envelope image (234) may be statistically normalized. In an
embodiment, the
-61 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
fluence in the ROI within the short envelope image (232) and the long envelope
image (234) may
be statistically normalized using a mathematical function. In an embodiment,
to statistically
normalize each pixel with the ROI of an envelope image, the value of that
pixel is divided by the
standard deviation for pixel values in the ROI. This normalization method is
used to compensate
for variation in the actual fluence of light on a specific target within the
tissue, because the actual
fluence is unknown, and may vary from person to person as well as from laser
event to laser
event. Once statistically normalized the ROI generally reflects qualitative
information
concerning the target tissue or volume. The physical justification for the
normalization is not
based on OA principles, but rather, the effect of the operation is to
normalize the histogram of
each of wavelength in the region of interest, based on an observation that the
width (standard-
deviation) of the histograms for each wavelength tend to be invariant under
certain conditions.
Moreover, although the laser fluence may not be accurately quantified at
depth, the histogram
width between wavelengths is believed to have some general stability with
regard to other
unknowns.
[00208] In an embodiment, smoothing (920) may be performed on the images
via a two
dimensional convolutional filter. In an embodiment, the two dimensional
convolutional filter
kernel may be based on an adjustable parameter. In an embodiment, the filter
kernel parameter
defaults to Gaussian. In an embodiment, the Gaussian or other filter kernel is
separable which
may permit more efficient implementation. In an embodiment, the smoothing
kernel may provide
a facility to permit focus on objects of a particular size or scale, which may
be related to a
feature-size selection. In an embodiment, a feature-size selection kernel may
be a bandpass
filter. In an embodiment, the system performing processing on the optoacoustic
data, and/or the
system displaying the optoacoustic output ¨ which may, but need not be the
same as the system
acquiring the sinogram ¨ would provide the operator the ability to select the
adjustable parameter
upon which the two dimensional convolutional filter kernel is based. The
filter kernel may be
applied to parametric images or to the envelope images or to the complex-
valued image. In an
embodiment, the filter kernel may be applied at any stage of processing.
[00209] The following processing steps are an illustrative embodiment of
smoothing:
a. Compute a filter kernel according to the dimensions of the image, the
kernel type
and the scaling parameter, sigma;
b. Use the kernel to perform two dimensional symmetric convolution with the
data.
- 62 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00210] A hemoglobin calculation (950) process may be performed using the
short and
long envelope images. In an embodiment, the normalized, smoothed short and
long envelope
images (922, 924) are used in the hemoglobin calculation (950) process along
with a 2x2 matrix
of hemoglobin coefficients. The hemoglobin coefficients, referred to following
as kll, k12, k21
and k22, are in proportion to the pseudo-inverse absorption coefficients for
hemoglobin or blood.
In an embodiment, the forward absorption coefficients may be used in the
derivation of the
hemoglobin coefficients and would pertain to the absorption of oxygenated and
deoxygenated
blood or hemoglobin at each of the short and long wavelengths and may also
account for the
absorption of water and other absorbers. In an embodiment, the pseudo-inverse
coefficients may
instead be arrived at directly or may be empirically tuned or adjusted. In an
embodiment, the
pseudo-inverse absorption coefficients may also take into account expected
values of other
absorption material in the tissue. This methodology can be extended to
situations where more
absorbing materials exist or where more laser wavelengths are used. The
computation can also
be applied for different absorbers. This methodology can be extended to
situations where more
absorbing materials exist or where more laser wavelengths are used. As further
illustrated in the
Appendix, in an embodiment, the pixels of the grayscale hemoglobin map (730)
may be
computed on a pixel by pixel basis as (k11+k21) * short image + (k21+k22) *
long image.
[00211] A remove common noise (930) process may be performed using the
short and
long envelope images. In an embodiment, the normalized, smoothed short and
long envelope
images (922, 924) are used in the remove common noise (930) process. An
illustrative
embodiment of a process to remove common noise is presented in pseudo code in
the Appendix.
In an embodiment, the remove common noise (930) process produces normalized,
smoothed,
common noise removed, short and long envelope images (932, 934). In an
embodiment, these
images (932, 934) are then used by the oxygenation calculation (950) process
along with a 2x2
matrix of oxygenation coefficients. The oxygenation coefficients, referred to
following as kll,
k12, k21 and k22, are in proportion to the pseudo-inverse absorption
coefficients for hemoglobin
or blood. In an embodiment, the forward absorption coefficients may be used in
the derivation of
the hemoglobin coefficients and would pertain to the absorption of oxygenated
and deoxygenated
blood or hemoglobin at each of the short and long wavelengths and may also
account for the
absorption of water and other absorbers. In an embodiment, the pseudo-inverse
coefficients may
instead be arrived at directly or may be empirically tuned or adjusted. In an
embodiment, as
discussed above for a hemoglobin calculation process, the pseudo-inverse
absorption coefficients
- 63 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
may also take into account expected values of other absorption material in the
tissue. As above,
the computation can also be applied for different absorbers. As with the
methodology for
performing a hemoglobin calculation process, this methodology as well can be
extended to
situations where more absorbing materials exist or where more laser
wavelengths are used. As
further illustrated in the Appendix, in an embodiment, the pixels of the
grayscale hemoglobin
map (730) may be computed on a pixel by pixel basis as (kl l+k21) * short
image / ((kl l+k21) *
short image + (k12+k22) * long image). In an embodiment, this equation may
further be
modified with the constant terms k01 and k02 such that the computation on a
pixel basis becomes
(k01+ (k11+k21) * short image)/ (k01+(k11+k21) * short image + k02+(k12+k22) *
long image). In an embodiment, the terms k01 and k02 are computed from a
statistical function
of a region of interest.
[00212] Other methods for computing parametric maps may be used in place
of the
methods described above. In an embodiment, multiple laser wavelengths can be
fired at the same
moment in a single frame, with the frame in its entirety corresponding to a
measurement event.
The molecular concentrations may be decoded by analyzing several measurement
events with
different combinations of fired laser wavelengths in each measurement event by
using
Frequency-Hopping Spread Spectrum or other similar techniques. In an
embodiment, multiple
laser wavelengths can be fired in a single frame, but not at the same moment,
wherein molecular
concentrations can be determined by analyzing the frame using Blind Source
Separation or
similar techniques. The multiple wavelength single frame approach can improve
sensitivity to
motion. In an embodiment, the analyzing steps may include solving systems of
absorption
equations from laser wavelengths to determine molecular concentrations in one
or more portions
of the volume.
Generate Parametric Images (240) - Denoising (735)
[00213] Returning to Figure 7, applying a denoising (735) process may
remove noise
having characteristics similar to Gaussian white noise. In an embodiment, with
the grayscale
oxygenation and hemoglobin maps (725, 730) created, a denoising (735) process
is applied to the
maps in the wavelet domain. In an embodiment, a denoising (735) process may be
alternatively,
or additionally, applied to real or complex sinograms and/or real or complex
images. Regardless
of the subject (e.g., maps, images or sinograms), the denoising (735) process
may be applied to
different areas of processing.
- 64 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00214] In an embodiment, a multi-spectral denoising procedure may be
used, which uses
information from more than one optical wavelength to reduce noise. In an
embodiment, multi-
spectral denoising may denoise using information from different sampled
datasets, such as, for
example, two sequential maps, images or sinograms, two non-sequential maps,
images or
sinograms, or from maps, images or sinograms resulting from different
wavelength light events.
[00215] In an embodiment, a denoising (735) process may operate in the two
dimensional
wavelet transform domain. In an embodiment, the wavelet denoising is based on
a thresholding
operation in the wavelet domain coefficients. In an embodiment, a complex-
valued two
dimensional wavelet transform may be used. In an embodiment, wavelet
thresholding via the
bivariate shrinkage method may be applied for noise reduction.
[00216] The following processing steps are an illustrative embodiment of
denoising:
a. Optionally, extend the boundaries of the image, (e.g., by using a symmetric
extension)
b. Compute the two dimensional wavelet transform of the image, (e.g., a two
dimensional complex dual-tree wavelet transform)
c. Threshold the coefficients in the wavelet domain according to an adaptive
or fixed
thresholding function, the thresholding function may be based on
characteristics
of the image, signal, wavelet coefficients and/or statistical properties
thereof,
d. Compute the inverse two dimensional wavelet transform of the modified
coefficients,
e. Delete any extended boundaries of the image to return an image of the
original
size.
[00217] In an embodiment, the denoising (735) process will return a
denoised version of
the input, having the same dimensions as the input, such as, for example, a
denoised grayscale
oxygenation map or a denoised grayscale hemoglobin map.
Generate Parametric Images (240) - Statistical Color Mapping (740)
[00218] The statistical color mapping (740) process is performed in an
embodiment to take
a grayscale (e.g., single-image-channel (as compared with, for example, a 3-
image-channel RGB
image)) map, and provide color to highlight data believed to be more
meaningful, and in an
additional embodiment provide a transparency mask that can be used to obscure
the visibility of
specific pixels. In an embodiment, the statistical color mapping (740)
consists of four stages,
namely calculating statistics for the ROI, generating a color mapping,
interpolating the map, and
- 65 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
generating a transparency mask. In an embodiment, the statistical color
mapping (740) consists
of three stages, namely calculating statistics for the ROI, generating a color
mapping and
generating a transparency mask, as the stage of interpolating the map being
optional, particularly
where the map has sufficient color depth (i.e., a sufficient number of colors)
to render the stage
reasonably superfluous.
[00219] In the calculating statistics stage, statistics of the
computational region of interest
are calculated to be used as calibration or reference points in the color
calculation. In an
embodiment, the mean and the standard deviation are calculated in this stage.
As discussed
above, the ROI may be any shape. In an embodiment, the ROI is specified by a
value, e.g.,
Boolean value, for each pixel in the parametric map to indicate if that pixel
is part of the
computational region of interest; thus calculation is not limited to
rectangular shapes, nor even to
a contiguous ROI. In an embodiment, the ROI may correspond to specific pixels
in the image
that meet one or more criteria, such as, e.g., pixels determined to have at
least a threshold level of
hemoglobin content, or other such molecular or physiological indicator based
on criteria. The
criteria for such ROI pixels may include those criteria which may be useful
for computation or to
enhance the contrast or other aspects of the display.
[00220] In the generating a color mapping stage, a color mapping is
generated from the
grayscale (e.g., single-image-channel) image to a predefined color map. The
color map
determines an ordered list of colors (e.g., RGB colors) that will be used to
represent information
in the output image. In an embodiment, a color reference point is initially
taken as the mean of
the computational ROI, plus an offset, where the offset is calculated by the
dividing the color
offset bias parameter by the standard deviation of the ROI. Then, using the
statistical
information, color limits are calculated. Color limits are numerical values of
the parametric data
that correspond to the first and last indices in the color map. Color limits
may be defined in
relation to the standard deviation of the computational ROI about a computed
or user-supplied
reference parameter, such as a midpoint. In an embodiment, color limits may be
defined in
relation to the standard deviation of the computational ROI about its mean. In
an embodiment,
color limits are defined in relation to a measure of contrast, such as the RMS
contrast, Michelson
contrast, Weber contrast, a local image contrast metric (contrast compared
against a filtered
image) or other measure of contrast, where the color limits are solved to
optimize or maximize
the measure of contrast in the computational ROI and thereby permit the
display of an Adaptive
Qualitative Image. In an exemplary embodiment, the RMS contrast is used. In an
embodiment,
- 66 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
upper and lower limit values are equal to the mean plus or minus the standard
deviation times a
color-contrast parameter. In an embodiment, the mapping to colors may be
achieved by relating
the lower limit value to the first value in the color map and the upper limit
value to the last value
in the color map, and linearly mapping the intermediate values of the
grayscale image between
such endpoints.
[00221] In an illustrative embodiment, the color mapping may be performed
by the
following steps, which may be expressed in more detail in the Appendix:
a. Compute the standard deviation of the region of interest
b. Set the color reference point to the mean of the region of interest plus
the bias
parameter divided by the standard deviation
c. Set the lower color limit to the color reference point minus the standard
deviation
times the color contrast parameter
d. Set the upper color limit to the color reference point plus the standard
deviation
times the color contrast parameter
e. Linearly map each pixel in the grayscale image to a color value in the
color map,
the lower limit value corresponding to the first index in the color map, the
upper
limit value corresponding to the last index in the color map, with values
beyond
the upper and lower limits saturating at the boundary colors, and the in-
between
values linearly interpolated between the upper and lower limits.
[00222] In the (optional) interpolating step, the color map is
interpolated. In an
embodiment, the color map is interpolated to smoothly map the intermediate
color values and
thus, prevent a choppy display. Using the color limits, the interpolating step
rescales the
parametric image onto the color map. In an embodiment, the color of each pixel
is set for
intermediate values by using linear interpolation between the two
corresponding adjacent colors
in the map. In an embodiment, the color map is provided in sufficient depth so
that the rescaling
does not require interpolation, but may provide the resolution required to use
a direct look-up.
[00223] The following processing steps are an illustrative embodiment of
linear mapping
and interpolating the color map, as expressed in more detail in the Appendix:
a. Set maximum color map index to corresponding to the last entry in the color
map
(i.e., the number of colors):
i. maximum colormap index = NumRGBColors - 1
- 67 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
b. Rescale the image so that the intensities correspond to the same numerical
range
as color palette for each pixel by row and column in the parametric map
i. B[row][col] = (parametric map[row][col] ¨ lower color limit range) * (
maximum colormap index)/(upper color limit range¨
lower color limit range)
ii. B[row] [col] = min(max(B[row] [col],0), maximum colormap index)
c. Compute the palette indices of each pixel of B by using the floor
function and call
the resulting array "index":
i. index[row] [col] = min(floor(B[row] [col]), maximum colormap
index)
d. If the color map has sufficient color depth, so that the effect of the
interpolation
would be negligible, the RGB value of the corresponding color map index may be
computed as rgb out[row][col] [component] = colormap(index [row] [col],
component). However, if this color map does not have sufficient color depth,
the
following steps may be performed:
i. Compute the remainder which is the difference between B and index and
call the resulting array "delta":
1. delta[row] [col] = B[row] [col] - index [row] [col]
ii. Use the value of delta to interpolate the RGB color channels onto the
provided color map:
1. For each color channel component (red, green, blue), set the color
component of each pixel in rgb out[row][col] to:
a. rgb out[row] [col] [component] =
colormap(index[row][col],
component)*(1-delta[row] [col]) + colormap(index+1,
component)*delta[row] [col]
e. Ensure that the values for the RGB colors are between 0.0 and 1.0 if the
RGB
values are represented by floating point values.
[00224] In the generating a transparency mask step, the transparency mask
is generated to
identify transparent portions of the map. The parameters lower transparancy
threshold and
upper transparancy threshold define the transparency threshold based on the
color limits
calculated in the interpolation step and the values present in the parametric
image. In an
embodiment, intermediate levels of transparency are used for pixel values
falling around the
lower transparency threshold or upper transparency threshold so that a gradual
fade from
- 68 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
transparent to opaque is provided rather than a hard cutoff In an embodiment,
a parameter for
opacity is used as a smoothing parameter, to smoothly render pixels in the map
rather than
having a hard threshold. As shown in the Appendix, the transparency may be
smoothly
transitioned using a calculate transparency mask subfunction. A predefined or
computed mask
may be used to make the map transparent in specific locations. In an
embodiment, a mask called
display roi (having dimensions the same as the map) would be false (e.g., have
a zero value) in
locations corresponding to pixels in a map that are to be completely
transparent. In an
embodiment, a pixel in display roi is false when it falls outside the ROI. In
an embodiment, a
pixel in display roi can be set to false to obscure the corresponding data in
the map, if the display
overlay should not be shown, such as, for example, where it falls outside of
boundary margins
which may be set for edges of the image.
[00225] In an embodiment, the output of the statistical color mapping
(740) process
comprises a 4 matrices that each comprise the same number of pixels as the
grayscale map, one
for a values of red, green and blue (RGB), and one as an alpha channel (A) or
transparency layer.
Thus, in an embodiment, the statistical color mapping (740) process receives
one matrix in the
form of a grayscale map, and returns four, that may be referred to
collectively as a RGBA data,
or a color map. Accordingly, the grayscale oxygenation map (725) is processed
by statistical
color mapping (740) to produce the RGBA data that collectively are referred to
as the
oxygenation map (250), and the grayscale hemoglobin map (730) is processed by
statistical color
mapping (740) to produce the RGBA data that collectively are referred to as
the hemoglobin map
(255).
[00226] The reference names, oxygenation map and hemoglobin map are not
intended to
suggest that the maps show all, or only, of the namesake material. Instead,
they are being used
for reference only. More specifically, although blood oxygenation is a
significant tissue property
displayed by the oxygenation map, and perhaps, but not necessarily the most
significant tissue
property displayed by the oxygenation map, it is within the scope of the
present disclosure that
the oxygenation map display no other tissue properties, and it is within the
scope of the present
disclosure that the oxygenation map display substantial additional tissue
properties. Likewise,
the hemoglobin map is so named only for reference, and the name is not
intended as a limitation
on the content. Instead, although hemoglobin is a strong optical absorber in
tissue, it is within
the scope of the present disclosure that the hemoglobin map display no other
tissue properties,
and it is within the scope of the present disclosure that the hemoglobin map
display substantial
- 69 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
additional tissue properties. In other words, the names are not intended to be
limitations,
however, they are believed to be representative of at least a substantial
portion of the molecular
indicators reflected in the map. In an embodiment, the statistical map
technique may be used to
display other indicators of the tissue as sources of contrast. In an
embodiment, the statistical map
technique may be used to display qualitative contrast based on a computed
spatially dependent
image representing the speed-of-sound, the optical absorption, the optical
scattering, the density
or other such computed parameter of the tissue. In sum, the present disclosure
section, as its
name implies, concerns statistical color mapping as part of generating
parametric ¨ or parameter-
based ¨ images. The examples showing an oxygenation map and a hemoglobin map
are just
provided for illustration.
[00227] Thus, as described above and detailed further below, a statistical
mapping method
is provided for producing a qualitative image. A qualitative image in this
respect is an image
substantially without numerical values specified, as opposed to a quantitative
image that has
numerical values specified.
[00228] In an embodiment, a system is provided that produces qualitative
images using
relative contrast, where the energy fluence profile in the volume is
sufficiently unknown or not
measurable, or may sufficiently deviate from a mathematical or computer model
of it. This
situation consequently results in an underdetermined set of equations, or loss
of accuracy, and
consequently prevents an accurate quantitative numerical solution of the
solved-for parameter, or
results in the case where the quantitative accuracy of the computed parametric
value is
substantially insufficient to support assigning a specific indicative
(diagnostic) color to specific
levels of a solved-for tissue parameter such as the absolute or relative
concentration of a
molecule. One problem that may arise is that the accuracy of the computed
concentration of a
specific local position may be dependent on the rates of absorption and
scattering of each optical
wavelength, which varies across subjects and with imaging depth. When such a
computation is
performed independently for each spatial position, the computed value may
deviate from the true
value enough to inaccurately display color when a fixed or non-statistical
mapping is used. To
handle this situation, a reference level is determined statistically against
the ordinary background
material contained in the volume within a region of interest. In one
embodiment, sufficiently
ordinary or reference breast tissue is used, the breast tissue having a
specific amount of
oxygenation (for example, above 80%), so the statistics of such background
tissue are used to
qualitatively compare the rest of the colorization against it, the mean of the
region of interest
- 70 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
representing the average background amount. It should be noted that some
phantoms with no
background absorption make the reference level procedure only affix to items
in the foreground
and not the background. However, the background in true tissue actively aids
in being able to
use reference level. The statistics of the background are also used to assign
the upper and lower
limits for the color.
[00229] The method in accordance with an embodiment of the invention
includes
depositing electromagnetic energy that is subject to variability into a
volume, measuring an
acoustic return signal from energy deposited in the volume, and computing a
parametric map that
estimates values of at least one parameter as spatially represented in the
volume. At least one
region of interest of the parametric map is defined. The region of interest
may represent a subset
of the parametric map, or the entire map. The method produces a mapping
configuration to
adjust for the effects resulting from at least some of the variability in the
spatial profile of the
deposited energy. The mapping configuration is produced by determining a
reference level
within the region of interest of the parametric map and then specifying an
upper color map limit
and a lower color map limit, with at least one of the upper color map limit or
the lower color map
limit being determined in relation to the reference level. The reference level
may be offset by an
offset value, and the offset value may be tunable by the user or fixed. The
parametric map is
then rendered in the palette of a color map by mapping estimated values of the
parametric map
onto the color map according to the upper and lower color map limits of the
mapping
configuration to produce a rendered parametric map, in accordance with the
procedures described
above. The rendered parametric map may then be displayed to the user. The
rendered
parametric map may be a representation of oxygen saturation, total opto-
acoustic return signal
intensity, or other property. In an embodiment, the rendered parametric map is
displayed as a
qualitative image, and consequently numerical values of the colorized
representation need not be
displayed with the image. That is, the colorscale of the parametric map is
displayed alongside
the parametric map bearing no numerical reference values to associate against
the colors.
[00230] Two or more wavelengths of energy can be applied by one or more
energy sources
to the volume so as to provide a source of molecular contrast for the
parametric map. Where
dual wavelengths are utilized, computing of the parametric map may include the
steps of
computing a spatial representation of the volume based on the acoustic return
signals for the first
of the two electromagnetic energy wavelengths, computing a spatial
representation of the volume
based on the acoustic return signal for the second of the two electromagnetic
energy
- 71 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
wavelengths, balancing the relationship between the computed spatial
representations for the two
electromagnetic energy wavelengths, estimating the values of at least one
parameter as spatially
represented in the volume based on the balanced spatial representations of
volume for each of the
at least two wavelengths, and outputting the estimated values of the at least
one spatially
represented parameter. In this respect, the balancing may be performed based
on a mathematical
characteristic applied to the region of interest of at least one of the
computed spatial
representations and then applying the result of the mathematical
characteristic to normalize at
least one of the computed spatial representations, thereby producing balanced
spatial
representations of the volume for each of the at least two wavelengths. The
mathematical
characteristic of the balancing may be a statistical function, and the
normalization may be
performed by multiplying the computed spatial representations in proportion to
the result of
statistical function. In an embodiment, the statistical function is the
reciprocal of the standard
deviation of the region of interest. In an embodiment, the result of the
statistical function is a
scalar value and the value that is used for multiplication is constant
throughout the region of
interest. The result of the statistical function may be a scalar value, and
the value that is used for
multiplication may vary spatially throughout the region of interest based on
the result of the
statistical function and according to a pre-determined relationship. Such pre-
determined
relationship is based on an assumed spatial energy distribution. In an
embodiment, the
mathematical characteristic of the balancing is the scalar projection of the
estimated values in the
region of interest for a first of the two wavelengths onto the estimated
values in the region of
interest for a second of the two wavelengths, and the normalization is
performed by multiplying
at least one of the computed spatial representations in proportion to the
result of the scalar
projection.
[00231] The parametric map may be computed by applying an implicit or
explicit model
of, or theoretical basis for, distribution of electromagnetic energy fluence
within the volume
pertaining to the two wavelengths. This may involve multiplying, dividing or
weighting the
respective return signals or image substantially by the energy fluence model
as a function of
depth or distance. The distribution of energy is responsible for the intensity
of the optoacoustic
return signal. The actual electromagnetic energy fluence caused by each
wavelength, as
distributed throughout the volume, has a propensity, due to variability within
the volume or
variability within a population of volumes, to differ from the modeled or
theoretical
electromagnetic energy fluence. The reference level may be determined using a
statistical
- 72 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
function of the numerical values of the parametric map within the region of
interest. The color
map may consist of one or more channels and the mapping step may include
mapping numerical
values of the parametric map onto each channel of the color map according to
the upper and
lower color map limits. The determination of the reference level may use a
particular
mathematical characteristic of the numerical values of the parametric map
within the region of
interest. The particular mathematical characteristic for determining the
reference level may be,
e.g., the mean of numerical values of pixels within the region of interest or
a fixed constant. The
particular mathematical characteristic for determining the reference level
also may be a statistical
function, such a standard deviation, a histogram, a maximum, a minimum, a
median, a
maximum-minimum/2, the proportion above a threshold, the kurtosis, the
skewness, the variance,
a range, or based on a measure of contrast such as Michelson, Weber, local or
RMS contrast.
Two or more wavelengths of electromagnetic energy may be deposited into the
volume, and the
step of computing a parametric map may be performed after the statistical
mapping. By
applying a theoretical basis of distribution of electromagnetic energy fluence
within the volume
pertaining to the two wavelengths, the distribution of energy responsible for
intensity of the
optoacoustic return signal may be factored into the computation. The rendered
map may be
masked with a transparency, and may be co-registered with an ultrasound image.
The co-
registration may involve motion estimation. User input may be used to specify
the region of
interest, such as by allowing the user to define a rectangle on an image. In
this respect, the user
input, which may be received via a graphical user interface, may be input
defining a top and
bottom depth, or a depth and a height which serve to define the top and bottom
depth. The
operator may adjust the region of interest in real time via the user
interface. The upper and lower
color map limits can be determined by computing a statistical function of the
numerical values of
the pixels of the region(s) of interest. Such statistical function may be the
standard deviation or
other such statistical function. The result of the statistical function is
used to proportion the
relationship that the upper and lower color map limits are from the reference
level. The upper
color limit may be defined as the reference level plus a first constant times
the standard deviation
of the region of interest, and the lower color limit may be defined as the
reference level minus a
second constant times the standard deviation of the region of interest. Of
course, the first
constant and the second constant may be the same constant. The reference level
may be fixed,
and the computation of the parametric map may be pre-calibrated or adjusted by
using fluence-
compensation on a per-wavelength basis. A transparency map and the upper and
lower color
-73 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
map limits may be defined in relation to the reference level. The transparency
map may be a
single-channel color map reflecting a transparency channel. The color map may
include a
plurality of colors, or may be a single- channel greyscale map.
Generate Parametric Images (240) - Combine Transparency Mask (750)
[00232] It has been observed that the measured optoacoustic return signal
from locations
with high hemoglobin content are the strongest. Thus, the signal-to-noise
ratio is highest in
regions of high hemoglobin. Moreover, it has been observed that focusing on
regions of high
hemoglobin content may be diagnostically useful. Accordingly, the combine
transparency mask
(750) process is designed to permit a later display of oxygenation from the
regions comprising
higher concentration of hemoglobin, and thus, having a higher signal-to-noise
ratio. In an
embodiment, parametric maps, may be combined synergistically with information
being
presented in the combined output that is not otherwise readily apparent or
observable in the
uncombined parametric maps, or obtainable from the uncombined parametric maps
independently.
[00233] In an embodiment, the combine transparency mask (750) process
calculates a
separate alpha channel, i.e., transparency mask, for the oxygenation data that
will constrain a
specific display of the oxygenation data to regions of higher hemoglobin
content, and thus to
regions having higher signal-to-noise ratio. In an embodiment, the separately
calculated alpha
channel (A) may be combined with the RGB data in the oxygenation map (250) to
form an
RGBA masked oxygenation map (260).
[00234] To calculate the separate alpha channel, and thus, the
transparency mask for the
oxygenation data that will constrain a specific display of the oxygenation
data to regions of
higher hemoglobin content, the A channel (e.g., transparency mask) from the
oxygenation map
(250) and the hemoglobin map (255) are combined. In an embodiment, the RGB
data from the
oxygenation map may be replicated and stored with the combined transparency
mask. In an
embodiment, when the masked oxygenation map (260) is rendered, the RGB data
from the
oxygenation map (250) can be accessed.
[00235] In an embodiment, to calculate the separate alpha channel for the
oxygenation
data, the A channel (e.g., transparency mask) from the oxygenation map (250)
and the
hemoglobin map (255) may be weighted. In an embodiment, where the alpha
channel from the
oxygenation map (250) and the hemoglobin map (255) are stored as real values
between 0 and 1,
the oxygenation map (250) and/or the hemoglobin map (255) may weighted by a
positive
- 74 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
exponent, and the two weighted masks are then multiplied together to produce
the masked
oxygenation map (260) alpha channel. Where the alpha channel from the
oxygenation map (250)
and the hemoglobin map (255) are stored as integer values, in an embodiment,
they may be
scaled prior to exponent weighting and multiplication. In an embodiment, the
oxygenation map
(250) and the hemoglobin map (255) alpha channel data are weighted, multiplied
and then scaled.
Coregister Maps With Ultrasound (265)
[00236] The coregister maps with ultrasound (265) process coregisters the
parametric
oxygenation map (250), hemoglobin map (255) and/or masked oxygenation map
(260) with an
acquired ultrasound image (step 215). In an embodiment, the parametric maps
being co-
registered and the acquired ultrasound image are scaled to fit the desired
size of the final output,
and then a blended overlay with the acquired ultrasound image, based on the
alpha transparency
channel of the respective parametric map. In an embodiment, the system
performing processing
on the optoacoustic data, and/or the system displaying the optoacoustic output
¨ which may, but
need not be the same as the system acquiring the sinogram ¨ would provide the
operator the
ability to select a desired size of the final output.
[00237] The following processing steps are an illustrative embodiment of
coregister maps
with ultrasound, as expressed in more detail in the Appendix:
a. The RGB ultrasound image, which may be defined by a rectangle or other
shape
is interpolated or scaled to fit the co-registered output image.
b. Each RGBA map (e.g., 250, 255 and/or 260) to be coregistered, is
interpolated or
scaled to fit the co-registered output image. The scaled RGBA map is overlaid
on
top of scaled ultrasound image using the blending function based on the
associated
alpha channel.
Method for Creating and Displaying Images
[00238] In an embodiment, the present disclosure includes a method for
display of
information within the optoacoustic return signal is provided. In an
embodiment, a method for
the qualitative display of molecular information reflected by an optoacoustic
return signal is
provided. In an embodiment, a method for the qualitative display of molecular
information
reflected by image statistics of an image reconstructed from an optoacoustic
return signal is
provided.
- 75 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00239] In an embodiment, the present disclosure includes a parametric map
(a.k.a.
parametric image) concerning molecular information in tissue that is computed
(as an input to or
component of this approach). Because of the variability in the nature of how
light penetrates into
tissue in vivo and/or due to an underdetermined set of equations from the
measured data,
however, the values in the resulting parametric map are difficult to
calibrate. It is thus an
objective that the molecular information may be displayed in a useful, and
potentially clinically
useful, qualitative fashion, based on relative values of a parametric map
and/or statistical
information of the parametric map. In an embodiment, an ideal parametric map
may be the
oxygenation saturation of hemoglobin in tissue, including, e.g., breast
tissue. The purpose is to
display clinically useful information and compensate for underdetermined set
of equations
resulting from a lack of complete information, such as, for example: having
less information, or
fewer lasers, than may be required to account for all unknowns in computation;
and varying
patient specific absorption/scattering, skin/tissue properties and morphology,
physiology,
structures, geometry, etc.
[00240] In an embodiment, the following steps may be used to implement a
computer
processing algorithm to accomplish the foregoing objective.
a. Acquiring data including a plurality of short sinograms (205), long
sinograms
(210) and ultrasound images (215);
b. Preprocessing the sinogram data (220)
c. Reconstructing images from the processed sinogram data (225)
d. Processing the reconstructed images (230), and producing long and short
envelope
images (232, 234);
e. Creating parametric maps;
f. Pre-processing of a parametric map may be done as a step (i.e. noise-
removal,
smoothing, statistical normalization)
g. Calculating a color reference point based on statistical information of a
region of
the parametric image (for example, the mean of the region plus and adjustable
bias
offset).
h. Determining a "color range" is calculated based on statistical information
of a
region of the parametric image (for example, the standard deviation of the
region).
i. Scaling and co-registering parametric map data onto a scaled ultrasound
or other
image; and
- 76 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
j. Displaying diagnostic information concerning the tissue examined.
[00241] Algorithms and equations useful for implementation the foregoing
are discussed
above and in the Appendix.
[00242] In biological tissue, blood is a strong absorber in the NIR range.
The calculation
for oxygenation of hemoglobin in tissue may involve a normalization term in
the denominator
which makes the calculation less sensitive to error. This results from the
approximation that oxy-
hemoglobin and deoxy-hemoglobin (i.e., the primary optical absorbers in blood)
are the full
contributors to the return optoacoustic signal. From this, in an embodiment,
it may be deduced
that the oxygenation calculation is sensitive to the spatially dependent
fluence-ratio between the
wavelengths, and not the spatially dependent total fluence of each wavelength
for a given point
(or depth) in the tissue.
[00243] Consider, for example, a linear model of the molecular energy
absorption
containing a (spatially dependent smooth) miscalibration term, and the
resulting model of the
calculated parametric image. Since the model equation is linear (or
approximately linear), the
mean and standard deviation are affected linearly by the miscalibration term
in the region of
interest. Hence, a statistical method is a way to bypass the miscalibration
term in a system
modeled with a miscalibration term. This, in an embodiment, mean and standard
deviation (and
other potential mathematical functions) when transformed by the model remain
stable in relation
to the other data, and in the presence of a miscalibration. Thus, in an
embodiment, even when the
data is miscalibrated, (constant fluence, depth dependent fluence) the
colorizations remain
relatively stable.
[00244] In an embodiment, the foregoing approach can be applied with
varied calibration
methods. In an embodiment, the foregoing approach may also be applied when
other various
signal processing, noise reduction, or other filters are used. In an
embodiment, the foregoing
approach may be used when co-registration and overlay are performed with other
modalities,
such as ultrasound. In an embodiment, the foregoing approach is applicable
even when varied
methods, including more advanced methods, are used to calculate the parametric
map. In an
embodiment, the foregoing approach is applicable when the parametric map is
well calibrated,
but the unknowns such as light penetration or undetermined equations still
exist. In an
embodiment, the foregoing approach is applicable when the parametric map is
well calibrated,
but the unknowns such as light penetration or undetermined equations still
exist, but are
compensated for using another method, such as by estimating the unknowns; by
explicitly
- 77 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
solving for the unknowns; by solving a minimization problem to obtain the
unknowns; or
otherwise. In an embodiment, the foregoing approach is applicable to map
quantitative images
(i.e. a calibrated parametric map) where the reference point is fixed and not
statistical. In an
embodiment, the foregoing approach is applicable to map quantitative images
(i.e. a calibrated
parametric map) where the color range is fixed and not statistical. As
discussed elsewhere
herein, the addition of another laser wavelength, in effect, reduces the
number of unknowns.
[00245] In summary, the foregoing approach provides statistical color
mapping and
relative (i.e., qualitative) images.
[00246] In an embodiment, the present disclosure includes a method for
calibrating
oxygenation or hemoglobin calculation in a dual wavelength optoacoustic system
is provided by
applying at least a plurality of the following steps:
a. using reference points, or reference regions
b. applying calculations - as described herein, or other such calculations
that are
extensions of the calculations described herein, or as will be apparent to one
of
skill in the art in view of the calculations described herein
c. compensating for the effect of light passing through skin layer,
coupling medium,
tissue
d. compensating for differences in scattering, absorption; penetration depth
in a two
dimensional image; a three dimensional volume of tissue with a two dimensional
cross section from light bars, a predefined light distribution, or a
dynamically
measured light distribution;
e. calibration from artifacts, including, differences in artifacts from
arteries or vein
f. applying an alternate detection scheme (automatic or manual) to find
locations of
veins or arteries in advance of calibration, which locations can be used for
calculation
g. using co-registered ultrasound data to provide information supplemental to
the
optoacoustic return signal and its derivatives
h. compare the intensities in the regions or reference point at one wavelength
(for
one or more types of structures/tissues) against (at least) the regions or
reference
points at a second wavelength (and potentially additional wavelength(s)) and
- 78 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
i. use the comparison to compensate for the intensity ratio (fluence ratio)
between
each wavelength with respect to depth and the absorption or scattering values
of
the tissue
[00247] In an embodiment, for the step of using reference points or
reference regions, such
points or regions may correspond to: blood vessels; tissue; the skin layer;
other known structures;
depth; wavelength specific absorption of light through vessels (because light
penetrates through
arteries differently than through veins and hence can be identified and
discriminated in an
image); or a reference point in one or more different images. In an
embodiment, the intensities in
the regions or reference point at a plurality of wavelengths are compared for
the purpose of
compensating for at least one of the following: the intensity ratio (fluence
ratio) between each
wavelength with respect to depth (and/or position); and the absorption or
scattering values of the
tissue. In an embodiment the mean, standard deviation or other such
mathematical characteristic
of a reference region may be used in the calculation. In an embodiment, the
characteristics of a
region at one wavelength, are compared against the characteristics of a region
at a second
wavelength, and furthermore compared against known absorption parameters under
presumptions
of tissue composition; by fixing the presumptions of tissue composition, the
system of equations
becomes solvable to compensate for the unknown fluence or fluence ratio.
[00248] In an embodiment, presumptions of tissue composition may include
using typical
ranges or values for tissue properties such as arteries, veins, vessels,
background tissue, fat,
muscle, or other known tissue or structures; the properties can include
optical properties,
mechanical properties, and/or other such known properties. These presumptions
can yield
assumptions about the nominal optical absorption for each wavelength. The
nominal optical
absorption can be useful in compensating for unknown fluence distribution.
Thus, in an
exemplary embodiment, presumptions may include that ordinary background breast
tissue
consists of blood which is predominantly at approximately 80% blood-oxygen
saturation, and
nominal amounts of water and no other significant absorbing molecules. In
another exemplary
embodiment, presumptions may include that the nominal blood-oxygenation values
of arteries
(90%+) and veins (60% to 80%), combined with the hematocrit levels and other
physical
properties of vessels yield values for the expected optoacoustic return signal
at each wavelength,
which can be used to calibrate for the unknown fluence distribution profile.
For example, a
blood-to-water ratio can be defined to represent the nominal proportion of
blood to water in a
vessel or it could also represent the ratio of blood to ordinary tissue under
the assumption of
- 79 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
tissue with optical absorption properties similar to water, for example tissue
comprising 20%
blood and 80% water. Further, if blood is assumed to be nominally oxygenated
to a value such as
80%, then a nominal optical absorption coefficient can be found for each
wavelength from the
nominal proportions of water, oxy- and deoxy-hemoglobin, based on assumed
tissue
composition. Thus, in an embodiment, nominal optical absorption coefficients
can be computed
for each wavelength for a region with presumed composition by summing the
weighted
contributions from each of its constituents. For dual wavelengths, the ratio
of nominal optical
absorption can be computed. In an embodiment, for a local region that is
presumed to conform to
known tissue composition, the ratio of actual return signals can be multiplied
with the nominal
optical absorption ratio to serve as a fluence correction estimate factor. In
an embodiment, the
fluence correction estimate factor can be spatially smoothed, in order to form
an estimate for
spatial fluence compensation of the parametric map. Alternately, in an
embodiment, vessel
regions can be assumed to have known composition, and thus be used to
calibrate the spatial
fluence by curve fitting a fluence model to the determined fluence correction
estimate factors. In
an embodiment, such fluence compensation may also be done in other similar
ways to this
example. In an embodiment, the blood-to-water ratio or blood oxygenation may
be adjustable by
a user interface. In addition, this example helps to illustrate some concepts
that may be applicable
to using a statistical method of color mapping, if known composition may be
variable. In an
embodiment, other methods of fluence compensation models are also possible.
[00249] In an embodiment, the present disclosure includes a method for
compensation of
light distribution in a clinical optoacoustic imaging system is provided that
performs such
compensation using: one dimensional curves; simulated curves; measured curves;
or a region of
interest specific method. In an embodiment, the compensation may be fixed, or
may be manually
operated. Additional details of the compensation method are described above.
[00250] In an embodiment, a graphical user interface (GUI) is provided for
operating a
clinical optoacoustic system, the GUI including, without limitation: controls
that permit operator
selection of a region of interest or operator selection of the criteria for a
region of interest; and to
adjust display parameters. In an embodiment, such controls may include but are
not limited to
performing the following adjustments: the color contrast parameter; the
selection of fluence
compensation curves; the color reference point bias parameter; upper and lower
color
transparency thresholds; a parameter to adjust the amount of smoothing; other
compensations for
absorption, filter, reconstruction, and display parameters; and a gain
parameter.
- 80 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00251] In an embodiment, a system is disclosed that does not attempt to
fully determine
the exact fluence profiles of the light as it penetrates into the tissue.
Rather a simplification, using
approximative parameters for the fluence model are used (as described above)
to compensate for
the light penetration. In an embodiment, the simple parameters are initially
tuned to best
approximate the light distribution for the majority of patients. If necessary,
the parameters can be
fine-tuned with a user-interface or using automatic methods. Collectively, the
set of parameters
that are used to compensate for how light penetrates into tissue (whether
manually or
automatically produced or tuned) are referred to as the "fluence assumptions".
In this situation it
is noted that the functional parameters displayed will be most precise in
comparing the functional
information of structures that are properly compensated by the fluence
assumptions. Situations
where the fluence assumptions may hold well include, without limitation:
a. where there are strong differences in oxygenation between two compared
structures with respect to the ROI;
b. when two compared structures are near each other and can be assumed to have
similar fluence, provided that the shadow of a strong optical absorber does
not
interfere with the fluence assumption;
c. when there is high contrast between the structure and the background
tissue of the
ROI;
d. when the structures being compared have high optical absorption;
e. when the presence or absence of other sources of high-contrast structures
in ROI
of the functional map are statistically common in the images which are
compared;
[00252] In an embodiment, the system and method disclosed may detect
relative or
qualitative differences in oxygenation (or molecular concentrations) within
the tissue. In an
embodiment, where the displayed values are not mapped precisely in a
calibrated manner on to a
fixed value of blood oxygen saturation or blood volume (which would require
full knowledge of
the fluence profile) it is nonetheless possible to display the contrast of the
functional parameters
within the tissue, using methods as described above. In this manner, the
methods and systems
described above, are also able to produce clinically useful qualitative
medical images. In an
embodiment, the information may be displayed graphically, using color to
display the quantity
without presenting the operator with a numerical value corresponding to the
color mapping,
having a useful display of qualitative optoacoustic information, and without
the direct
presentation of corresponding numerical values. In an embodiment colors are
displayed in a
- 81 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
manner that they do not need to correspond to any particular fixed value, but
rather, the colors
may adjust automatically to display the maximized contrast based on
information contained in
the current image. For example, the color green need not correspond to a fixed
value, e.g., 80%
oxygenation, but instead, may be a representation of relative or of
qualitative information. In an
embodiment, the methods of fluence compensation and calibration can be used to
produce more
accurate quantitative images.
[00253] In an embodiment, the present disclosure includes an apparatus for
detecting
tumors or other structures or anomalies based on functional morphological
information, rather
than merely displaying colors. In an embodiment, the present disclosure
includes an apparatus
for qualitatively detecting tumors or other similar structures based on
functional morphological
information, rather than merely displaying colors.
[00254] In an embodiment, pattern classification or such techniques may be
applied to the
methods of calibration, qualitative imaging or relative imaging above. In an
embodiment, a set
of predetermined rules or guidelines may be used for interpretation of the
images generated by
the above systems and/or method. In an embodiment, a clinical system may
include the rules or
guidelines for the purpose of automatically applying the same, or for
assisting an operator to
manually apply them. In an embodiment, a system with a feature vector assembly
module for
assembling a feature vector concerning a lesion comprising an ordinal
classification of a plurality
of features of a lesion, the plurality features selected from the set of: 1)
internal vascularity and
de-oxygenation, 2) peri-tumoral boundary zone vascularity and deoxygenation,
3) internal
deoxygenated blush, 4) internal total blood, 5) external peri-tumoral
radiating vessels, and 6)
interfering artifact; and a feature vector classifier for calculating a
diagnostic measure of an
outcome for a lesion based on a feature vector concerning the lesion. In an
embodiment, the
feature vector assembly module may contain an identification module for
identifying the
presence of each of the plurality of features of a lesion; and a
quantification module for
computing an ordinal classification for each of the plurality of features
present in a lesion. In an
embodiment, the lesion identification module may comprise a pattern search
module for
identifying, based on the characteristics of a lesion, the presence of a
lesion in the at least one
image. In an embodiment, a diagnositic outcome may be produced by inputting
the produced
feature-vector into a feature-vector classifier designed to operate on the
feature vector. In an
embodiment, a system for automatically analyzing an opto-acoustic image for
the presence of
features, involving a training phase, and a feature detection phase may be
used to output the
- 82 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
feature strength of each spatial position of an image to be used as input for
the feature-vector
assembly module.
[00255] Turning now to Figures 10, 11 and 12, and with reference to Figure
2 as well,
four-image illustrative displays are shown. The image displayed in the upper
left is an
embodiment of short envelope image (232) with a identified rectangular region
of interest. The
image displayed in the upper right is an embodiment of a long envelope image
(234) with the
same identified rectangular region of interest. The image displayed in the
lower left is an
ultrasound image (295) also showing the identified rectangular region of
interest. The image in
the lower left is one embodiment of a display of coregistered ultrasound image
and oxygenation
map (275). On the right hand column of the four-image display are the value
for various
illustrative parameters that, in an embodiment, can be operator selected.
[00256] Turning now to Figures 13, 14 and 15, and with reference to Figure
2 as well, six-
image illustrative displays are shown. The top left is an ultrasound image
(295), the bottom left
and center are embodiments of short and long envelope images (270, 290). The
top center image
is an embodiment of a display of a coregistered ultrasound image and
oxygenation map (275), the
top right image is an embodiment of a display of a coregistered ultrasound
image and
hemoglobin map (280), and the bottom right image is an embodiment of a display
of a
coregistered ultrasound image and masked oxygenation map (285).
[00257] In an embodiment, colorization on an image shows relative
oxygenation, thus, for
example, red may mean an area is less oxygenated than the surrounding tissue
and green may
mean it's more oxygenated. In an embodiment, molecular optical contrast
provides
differentiation between hypoxic blood of breast carcinomas (which may be shown
in red) and
normally oxygenated blood in benign masses (which may be shown in green).
Playback Mode
[00258] As noted above, the Laser Optic Movie (LOM) is a collection of
recorded data
that may be recorded in groups of related files, or more preferably, in a
single data file. In an
embodiment, the disclosed system may include an offline (e.g., non-live)
playback mode in
addition to the live display modes described. In this respect, when the system
is displaying data
in the online mode, the live display may be paused, rewound to an earlier
point in the LOM file
described above, and an earlier portion of the LOM can be processed using one
or more different
system parameters and played back. Thus, the unprocessed data in the LOM can
be used to
playback the same scan as was previously viewed live, but with different
processing so as to
- 83 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
convey different information in the image than is displayed on the display
during live mode. The
user input devices 116 (FIG. 1) in the control panel of the control and
display subsystem 2810
(FIG. 28) may include a trackball and various other input devices such as jog
dials, buttons and
conventional means for controlling video playback, as well as a graphical user
interface (GUI),
discussed above. A pause button may be included for pausing the live display
and entering into
playback mode. An "x seconds back" button may be provided for rewinding the
time that is
currently being displayed by x seconds. For example, if the system is in live
mode and such
button is configured as a "five-seconds back" button, then actuation of such
button causes the
system to enter playback mode and begin playback of images produced from data
taken five
seconds prior to the button being actuated.
[00259] For the playback mode, the raw data that has recently been
acquired is stored in a
large buffer. In an embodiment, when the user clicks "pause" in the GUI, the
playback mode is
initiated and the system can regenerate prior frames from raw data, while
changing parameters to
modify the processing used to generate the prior frames. Using the GUI in
combination with the
trackball or other user input device allows the user to scroll to select a
frame or series of frames
for playback. As the frame or frames are being played back in a loop, the user
can adjust
parameters or modes of the system in order to see the frames with different
processing or in a
different format. The resulting movie, (or an individual processed/re-
processed frame), can be
exported to a file. This can be done in a batch, which allows for offline
processing from raw
data. The raw data itself can be exported to a file. The playback mode can be
configured to
allow only a certain set of user-selected frames, selected using the trackball
or other user input
device, to be exported to a file. In an embodiment, the system stores raw and
processed data on
the optoacoustic electronics subsystem 2804 (FIG. 28), and then sends them
over a network to
the ultrasound subsystem 2802 (FIG. 28), which overlays them and displays the
overlaid images
to the user; a protocol can be provided that performs this process. The
playback mode operation
can be configured to allow a user to scan in one mode (e.g., the six-image
display mode, shown
in FIGS. 13-15 and discussed above), switch modes, and replay in another mode.
One example
of the use of playback mode with the six-image display mode is as follows.
When the user is in
six-image display mode and pauses the live display thereby entering playback
mode, the system
can switch to a different display mode such as a single-image display that
allows the user to see a
single, larger image and focus on a particular region of interest.
- 84 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00260] The playback mode further allows the user to apply different
filters, tuned to find
different physiological features, to the same stored data. The playback mode
further allows a
different reconstruction algorithm to be used during playback or export. One
useful parameter
that can be changed in the playback mode is the ROI depth, described above. It
can also be
configured to allow the interframe persistant artifact reduction, discussed
above, to be applied to
the paused buffer.
Optoacoustic System and Method
[00261] Returning to Figure 1, generally, device 100 provides an
optoacoustic system that
may also be employed as multimodality, combined optoacoustic and ultrasound
system. In an
embodiment, the device 100 includes a probe 102 connected via a light path 132
and an electrical
path 108 to a system chassis 101. Within the system chassis 101 is housed a
light subsystem 129
and a computing subsystem 128. The computing subsystem 128 includes one or
more computing
components for ultrasound control and analysis and optoacoustic control and
analysis; these
components may be separate, or integrated. In an embodiment, the computing
subsystem
comprises a relay system 110, an optoacoustic processing and overlay system
140 and an
ultrasound instrument 150.
[00262] In an embodiment, the light system 129 is capable of producing
pulses of light of
at least two different wavelengths. In an embodiment, the light system 129
outputs should be
capable of producing short pulses of light in each of those wavelengths, e.g.,
a pulse lasting less
than about 100 ns, and potentially as short as about 5 ns. As will be apparent
to one of ordinary
skill in the art from this disclosure, the inventions disclosed herein may
also be practiced using
pulsed light comprising pulses lasting greater than 100 ns. In an embodiment,
the light source
129 includes two separate lights 130, 131. The output of the light system 129
is delivered to the
probe 102 via the optical path 132. In an embodiment, the lights 130, 131 are
lasers producing
light in the infrared, near-infrared, and/or visible spectrum. In an
embodiment, light 130 and
light 131 each produce light at a different wavelength in the infrared or near-
infrared spectrum.
In an embodiment, the optical path 132 used to deliver light from the light
source 129 to the
probe 102 is a fiber optic bundle comprising multiple strands of optical
fiber. In an embodiment,
the optical path 132 comprises sufficient optical fibers of sufficient size
(diameter) to carry a
short, high powered pulse of light to the distal end of the optical path 132.
In an embodiment, the
total pulse energy carried over the optical path 132 may be on the order of
one or more
millijoules. In an embodiment, the total energy per light pulse delivered from
the optical path
- 85 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
132 is less than about 100 millijoules. In an embodiment, the total energy per
light pulse carried
over the optical path 132 is in the range of about 10-30 millijoules, and the
optical path 132
comprises between about 1,000 and 2,000 optical fibers of between about 100
and 300 microns
each. In an embodiment, a single fiber can be used as the optical path. In
such embodiment, the
fiber may be 1000-1500 microns in diameter. Of course, the diameter of such
single fiber may
be smaller, e.g., 400 microns. Given the required total pulse energy carried
over the fiber, one
skilled in the art can calculate the diameter required of the fiber
accordingly.
[00263] In an illustrative embodiment, the light system 129 may use Nd:YAG
and
Alexandrite lasers as its two lights 130, 131, although other types or
wavelengths, and additional
lights, may also be used. Lights 130, 131 should be capable of producing a
short pulse of light,
e.g., a pulse lasting less than about 100 ns, and more preferably around 5 ns.
In an embodiment,
the two lights 130, 131 can be separately triggered. In an embodiment, the
light output by the
lights 130, 131 may be projected onto the same light path 132 through the use
of an optical
element 133 that generally permits one light 130 to pass through from a first
side to a second
side, while reflecting one light 131 that strikes the second side. The use of
optical element 133 or
a similar element permits the alignment of the output of two lights 130, 131
such as lasers onto
proximal end of the light path 132. In an embodiment, optical elements 133 can
align the light
output from more than two lasers, for example, through the use of multiple
optical elements 133.
[00264] Turning briefly to Figure 39 there is shown a schematic block
diagram illustrating
an embodiment of a light subsystem 129 for use in a combined optoacoustic and
ultrasound
system. In an embodiment, light subsystem 129 comprises two light sources 130,
131 each
capable of generating a light pulse; the output of each of the two light
sources 130, 131 is
directed to an optical attenuator 3902, 3912,a sync detector 3903, 3913, and a
power detector
3904, 3914. If the light is not already aligned at appropriate angles, one or
both of the beams of
light may be redirected, e.g., by mirror 3915, and then, the light originating
at the light sources
130, 131 is passed into a combiner 133 that redirects the light onto a common
path. The common
light path may then be passed through a homogenizer 3906, and/or an aperture
3907. After
exiting the aperture, if the combined light path is not already aligned at the
appropriate angle and
location to exit a light output port, the light may once-again be redirected
by the use of one or
more mirrors (not shown).
[00265] Generally, the optical attenuators 3902, 3912 may be provided to
attenuate the
light pulse generated by the light sources 130, 131. Typical light sources
130, 131, may include
- 86 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
a Q-Switched Nd:YAG laser and an Alexandrite Q-Switched laser. Such lasers may
not permit
the kind of fine output attenuation required for an optoacoustic application
as described herein.
Accordingly, an optical attenuator 3902, 3912 is used. In an embodiment, the
optical attenuators
3902, 3912 each comprise two layers of polarized material that are rotatably
mounted with
respect to each other. In an embodiment, an external signal controls a small
motor, which in turn
adjusts the angle of one layer with respect to the other, and thus, the amount
of light that is
transmitted there-through. In an embodiment, one layer is a fixed sheet of
polarized glass and the
second layer is a round piece of polarized glass that can be rotated under
control of a small
electric motor. In an embodiment, the attenuator motor is controlled by the
optoacoustic
processing and overlay system 140 in connection with its processes controlling
light output from
the probe 102.
[00266] The sync detectors 3903, 3913 may be provided to generate a signal
when a light
source pulses. As discussed above, typical light sources 130, 131, may include
a Q-Switched
Nd:YAG laser and an Alexandrite Q-Switched laser. When using such pulse
lasers, which
require certain conditions to be met before they emit a pulse of light, the
command to fire cannot
be relied upon for synchronization as there may be delay, and potentially an
unpredictable delay,
between the command to fire and the actual pulse of light. Because, as
discussed elsewhere
herein, the acoustic sampling to detect the optoacoustic effect lasts less
than 100 microseconds,
precise timing is required, and thus, sync detectors 3903, 3913 are placed in
the optical path. In
an embodiment, a beam splitter (not shown) is used to redirect a small portion
of the optical pulse
into the sync detectors 3903, 3913 and allowing the vast majority of the beam
to continue on its
path. Since one sync detector is used for each light source, separate sync
signals may exist for
each. In an embodiment, a single sync detector could be used. In an
embodiment, a single sync
detector could be used, but the single sync detector may be designed to
distinguish between the
two light sources, and thus, itself, could generate separate sync signals for
each.
[00267] The power detectors 3904, 3914 may be provided to permit a
relative or absolute
determination of the amount of post-attenuation light that will travel through
a light path 132. In
an embodiment, a beam splitter (not shown) is used to redirect a small portion
of the optical pulse
into the power detectors 3903, 3913, but allowing the vast majority of the
beam to continue on its
path. In such an embodiment, the detected amount of power may be scaled to
determine the
emitted light source power.
- 87 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00268] The homogenizer 3906 may be provided to homogenize the beam of
light across
its section. In other words, that the fluence is approximately the same across
a known areas of
the beam. In an embodiment, the beam will be directed to a bundle of fiber
optic cable, and thus,
the beam is homogenized in an effort to ensure that the amount of light
entering each strand of
the fiber optic cable is reasonably the same as the amount of light entering
each other strand.
[00269] An aperture 3907 may be provided to ensure the appropriate
circumference of the
light beam for incidence upon the entry point of the light path 132.
[00270] Returning to Figure 1, in an embodiment, multiple light systems
and light paths
may be employed, with the light of each light system being carried on separate
fibers or fiber
groups that may be intermingled and/or randomized (discussed further below)
and/or grouped at
their distal ends. Intermingled, as used in this context, refers to the
mapping of the fibers in the
light path such that fibers are generally distributed in a relatively even
manner in the distal
groupings. Thus, a plurality of adjacent fibers on the proximal end of the
light path would
generally be about evenly divided in groupings on the distal end. As an
illustrative example,
where there are two distal groupings, any arbitrary selection of a sufficient
group of adjacent
fibers on the proximal end should be about evenly split between the two distal
groupings. The
randomization, intermingling and/or grouping need not take place at any
specific location on the
light path 132. In other words, for example, the division of a fiber cable
from one proximal
group to two distal groups can occur at any point along the light path 132, or
along substantially
the entire length of the light path 132. Similarly, the randomization and/or
intermingling need
not take place along the entire length of the light path, but rather, for
example, may take along a
the distance of, e.g., a few centimeters or more near either end of the light
path, or anywhere else
along the light path 132. Randomizing fibers between one end and the other end
of a light path
prevents a local anomaly affecting an adjacent group of the fibers on the
input from affecting an
significant adjacent group of the fibers on the output. Intermingling fibers
between one end and
the other end of a light path prevents a local anomaly affecting an adjacent
group of the fibers on
the input from disproportionately affecting one group or subgroup of fibers on
the output.
[00271] Where the light path terminates in multiple groupings (or
subgroupings) of fibers,
the distal ends of the groupings (or subgroupings) may be fused, or lapped and
polished, or just
secured together (removably or otherwise). In an embodiment, the distal end of
the light path is
formed into a plurality of groups that are spaced in such a manner so as to
permit light to emit on
each side of the transducer array. In an embodiment, the distal end of the
light path is formed
- 88 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
into a plurality of groups that are spaced in such a manner so as to permit
light to emit around the
entire transducer array. In an embodiment, the distal end of the light path is
formed into two or
more groups, and the two or more groups subdivided into subgroups that are
separately secured
by a light bar guide, which light bar guide may be associated with the group.
In an embodiment,
optical elements 133 can consist of optical elements that are used to measure
the light energy to
determine energy per light pulse.
[00272] Although the total energy per light pulse carried over the optical
path is in the
order of tens of millijoules, because the pulse of lights 130, 131 is so
short, the peak power
output over the optical path 132 is frequently approaching or in the megawatt
range.
Accordingly, the output of lights 130, 131 has the capacity to cause the
optical fibers and/or the
cladding on the optical fibers to burn, discolor or otherwise degrade. Such
degraded optical
fibers and/or cladding, whether burnt, discolored, or otherwise, can
exacerbate the problem as
they begin to transmit less light power and cause more heating. Accordingly,
in an embodiment,
sufficient number and size optical fibers are present in the optical path 132
to permit handling of
the peak power loads and avoid fiber burnout. To accommodate higher peak
power, a larger
fiber bundle can be used. It will be apparent to a person of skill in the art
that the peak power
capacity of a fiber bundle can be increased by increasing the number of
optical fibers, or the
diameter of optical fibers, or both. Notably, however, as the dimension of the
fiber bundle
increases, the weight and flexibility of the optical path 132 may become less
desirable.
Moreover, when using more optical fibers, or optical fibers of a larger
diameter, the output of
light source 129 must be delivered to the optical path 132 across the wider
diameter of the larger
bundle. In an embodiment, regardless of the ultimate size of the proximal end
of light path 132,
the output of light source 129 should be distributed sufficiently across its
cross section to prevent
burn out failures when operating in expected peak power ranges.
[00273] In an embodiment, the fibers of the proximal end of the light path
132 may be
fused to form a fused entry point to the optical path 132 for the output of
light source 129. In an
embodiment, the fiber ends can be fused by applying heat. In an embodiment a
fused end may be
surrounded with a metal ring. In an embodiment a fused end may be surrounded
with a stainless
steel ring. Once the proximal end of optical path 132 has been fused, it will
resist burnout at
substantially higher peak power. For example, using a fused end light path 132
may permit
carriage of three, four or even five times as much peak power. The ability to
carry substantially
higher peak power in a given optical path 132 permits use of a more flexible
and lighter fiber
- 89 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optic bundle to carry the same peak power as an un-fused optical path 132.
Thus, in an
embodiment, where a 'A" fiber optic bundle may have been required in an un-
fused bundle of
optical fibers forming an optical path, a 'A" fiber optic bundle with a fused
proximal end may be
used to carry the same peak power. A 1/4" fiber optic bundle with a fused
proximal end is
approximately 1/4 of the weight and much more flexible than a 'A" fiber optic
bundle. Moreover,
fusing of the proximal end of light path 132 may produce an even smaller fused
area to
illuminate using light source 132 as the fusing removes the inter-fiber spaces
that would have
existed in the bundled end of the round-cross-section optical fibers.
Accordingly, one or more of
the following advantages may be attained by fusing the proximal end of the
optical fibers
comprising the light path 132: reduced weight of the light path; increased
flexibility of the light
path; reduced failure; increased reliability; higher peak power capacity.
[00274] In an embodiment, the proximal end of the light path 132 may be
separated into
separate groups for separate lights 130, 131 in a light source 132, and light
output by the lights
130, 131 may be projected onto different proximal groups of the light path
132. More than two
separate lights may be used, and the proximal end of the light path 132 may be
separated into at
least one group for each light. Each group of fibers at the proximal end of
the light path 132 may
be fused together to form a fused entry point to the optical path 132 for the
light with which it is
associated. In an embodiment, the fibers of a light path having multiple
groups on the proximal
and are intermingled with respect to the groups or subgroups on the proximal
ends. In an
embodiment, the fibers of a light path having multiple groups on the proximal
and are
randomized with respect to the groups or subgroups on the proximal ends. In an
embodiment, a
light path is provided with a fused proximal end (input) and at least two
groups on its distal end
(outputs), the fibers being intermingled and randomized, thus preventing a
local anomaly
affecting adjacent fibers at the input of the light path from: (i) causing an
anomaly affecting a
substantial number of adjacent fibers on an output; and (ii)
disproportionately affecting one of the
outputs. In an embodiment, a light path is provided with at least two groups
on its proximal end
(inputs) and at least two groups on its distal end (outputs), the fibers being
intermingled and
randomized, thus preventing a local anomaly affecting adjacent fibers at an
input of the light path
from: (i) causing an anomaly affecting a substantial number of adjacent fibers
on an output; and
(ii) disproportionately affecting one of the outputs. In an embodiment, a
light path is provided
with at least two fused groups on its proximal end (inputs) and at least two
fused groups on its
distal end (outputs), the fibers being intermingled and randomized, thus
preventing a local
- 90 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
anomaly affecting adjacent fibers at an input of the light path from: (i)
causing an anomaly
affecting a substantial number of adjacent fibers on an output; and (ii)
disproportionately
affecting one of the outputs.
[00275] In an embodiment, optical fiber of the type that may be used in
light path 132
includes a transparent core surrounded by a transparent cladding material with
a lower index of
refraction. The core may be made from any transparent material, although
excellent results have
been observed using pure glass (i.e., silica). In an embodiment where a bundle
of optical fibers
are to be fused, the cladding may be removed in the area to be fused. In an
embodiment, the
cladding may be removed using a chemical process. For example, for some
cladding, hot
sulfuric acid or acetone may be used. The removal of cladding prior to fusing
reduces the chance
of particles of the cladding material becoming embedded in the fused end, as
such particles may
interfere with the light transmission across light path 132.
[00276] In an embodiment, the light output by the lights 130, 131 is sent
towards a fused
optical fiber bundle at the proximal end of light path 132 via an optical
path, which may include
optical element 133, internal to the light source 129. In an embodiment, light
source 129 is a
laser system capable of outputting laser light pulses, at one or a more
wavelengths, onto light
path 132. In an embodiment, light path 132 is a fiber optic bundle having a
fused end proximal
to the light source 129.
[00277] In an embodiment, the device 100 also comprises an electrical path
108 running to
and/or from the probe 102 to the system chassis 101. In an embodiment,
electrical path 108 runs
to and/or from the probe 102 to a relay system 110 within the system chassis
101. The electrical
path 108 may run near, alongside or coaxially with the optical path 132 from
the probe 102
toward their respective connections on the system chassis 101. In an
embodiment, the electrical
path 108 comprises a plurality of separate coaxial wires. In an embodiment,
the electrical path
108 is run in a common jacket with at least a portion of the optical path 132.
Running electrical
path 108 in a common jacket with at least a portion of the optical path 132
reduces the number of
cables running from the system chassis 101 to the probe 102. Running
electrical path 108 in a
common jacket with at least a portion of the optical path 132 may minimize the
diameter and
weight of, and increase the durability of, the combined cables (i.e., optical
path 132 and electrical
path 108) running from the system chassis 101 to the probe 102.
[00278] In an embodiment, the plurality of coaxial wires is woven around
at least a portion
of the optical path 132. As discussed above, many considerations go into the
number of separate
- 91 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optical fibers used in optical path 132. As discussed further below, numerous
design
considerations go into the number of separate electrical leads or traces
forming the electrical path
108. In an embodiment, there are about 256 leads (corresponding to 256
transducers) forming
the electrical path 108 and approximately 1,000 separate optical fibers
forming the optical path
132, making the fiber:lead ratio about 4:1. As will be apparent, it is
possible to comingle the
optical fibers and leads or traces in the electrical path in a variety of
ways, including, for
example, bundling a group of individual fibers with a single electrical lead
or trace, or bundling
proportionally larger groupings of fibers and leads together. In an
embodiment, the bundling of
fibers and leads or traces would be done generally in the proportion of
fibers:leads in the system.
[00279] One or more displays 112, 114, which may be touch screen displays,
are provided
for displaying images and all or portions of the device 100 user interface.
One or more other user
input devices 116 such as a keyboard, mouse, trackball, and various other
input devices (e.g.,
dials, buttons and switches) may be provided for receiving input from an
operator. As an option,
power and control signal lines 109 carry power to the probe 102 and control
signals between the
probe 102 and the computing subsystem 128.
[00280] In an embodiment, the connections between the probe 102 and the
system chassis
101 may be formed into a flexible cable, which may consist of the light path
132, the control
line(s) 109 and the electrical path 108. The flexible cable may be covered in
a common outer
jacket or sheath for convenience and ease of use. In an embodiment, a medial
portion of the light
path 132 forms the core of the single flexible cable, and medial portions of
the electrical path 108
and/or control line(s) 109, if any, may be wrapped or braided about the medial
portion of the
light path 132. In an embodiment, a common outer jacket or sheathing encloses
a fiber optic
bundle forming a medial portion of the light path 132, a coaxial bundle
forming a medial portion
of the electrical path 108, and control line(s) 109, if any. In an embodiment,
the fibers forming a
medial portion of the light path, and the wires forming a medial portion of
the electrical path 108,
as well as control line(s) 109, if any, may be intertwined or intermingled
with each other along
the medial portion of the connections between the probe 102 and the system
chassis 101.
[00281] In an embodiment, the distal end of the flexible cable(s)
connecting the probe 102
and the system chassis 101 is associated with, and non-removably integrated as
part of the probe
102. In an alternative embodiment, the distal end of the flexible cable(s)
connecting the probe
102 and the system chassis 101 is removably associated with the probe 102. To
removably
associate the flexible cable(s) connecting the probe 102 and the system
chassis 101 requires both
- 92 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optical fiber connection for the light path 102 and electrical connection for
the electrical path 108
and control line(s) 109, if any.
[00282] In an embodiment, the light path 132 is split into two sections,
and the two
sections are brought together using an optical fiber connector in close
proximity to the probe 102.
The optical fiber connector may be physically located within the probe 102, or
may span opening
404 (see Figure 4), or be located outside the probe 102. In an embodiment, an
optical fiber
connector would mechanically couple and align the cores of the fibers making
up the light path
132 so that light can pass from one section to the other without significant
loss. In an
embodiment, the facing ends of the two sections of the light path 132 are
fused, and may be first
stripped of cladding and then fused, to mitigate issues of core alignment.
Regardless of whether
the fiber ends are fused, the ends internal to light path 132 that are being
connected by the optical
fiber connector may be lapped and polished to improve light transmission. In
an embodiment,
probe 102 has a removable access panel that permits access to optical and/or
electrical connectors
located within the probe.
[00283] To support removability of the electrical path 108 and control
line(s) 109, if any,
removable electrical connectors may be provided. In an embodiment, flex
circuit is elongated so
that connectors 314 which are connected to the end of electrical path 108 are
accessible from a
removable access panel, thereby permitting the disconnection of electrical
path 108. In an
embodiment, electrical path 108 (and control path 109, if any) is split into
two sections, and the
two sections are brought together using an electrical connector in close
proximity to the probe
102. The electrical connector may be physically located within the probe 102,
or may span
opening 404 (see Figure 4), or be located outside the probe 102. In an
embodiment, an electrical
connector would electrically couple the two portions of the electrical path
108 so that signals can
pass from one section to the other without significant loss.
[00284] In an embodiment, the signals carried on the probe-side portion of
electrical path
108 are analog signals, and are terminated into an analog-to-digital
converter, and the signals
carried on the other portion of the electrical path ¨ the portion that
connects to the system chassis
101 ¨ are digitized representations of the analog signals carried on the probe-
side portion of the
electrical path 108. In an embodiment, the signals carried on the electrical
path 108 are digital
signals given that the analog-to-digital conversion is performed in the body
of the probe handle
[00285] In an embodiment, the optical connector(s) to connect the light
path 132 to the
system chassis, and the electrical connector(s) for the flexible cable(s) that
operationally connects
- 93 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
the system chassis 101 to the probe 102 may be integrated into a single
connector that can be
operated to quickly disconnect the probe 102 from the cable. In an embodiment,
an optical
connector connecting the light path 132 to the system chassis, and a multi-pin
electrical
connector for connecting the electrical path 108 and control line(s) 109 to
the system chassis are
provided as separate connectors. In an embodiment, the optical connector and
the multi-pin
electrical connector are designed to be hand operated permitting tool-free
removal by an operator
or maintenance personnel.
[00286] Turning briefly to Figures 36, 37 and 38, an unconnected view of
one embodiment
of the cable side of a fiber optic connector, a detail view showing the
ferrule of the connector,
and another detail showing the collar of the connector, is shown. A light path
3232 is terminated
at the distal end of a stepped ferrule 3607. In an embodiment, the distal end
3608 of the fiber
bundle forming the light path 3232 is fused and/or lapped and polished. The
stepped ferrule
3607 has an area of wider circumference 37A and an area of narrower
circumference 37B which
meet at the step. The area of narrower circumference is intended for insertion
within the light
output port (not shown) in the chassis side of the connector (not shown). A
collar 3606
substantially surrounds the area of wider circumference 37A of the ferrule
3608. In an
embodiment, a distal end of the collar 3606 is substantially flush with the
step in the ferrule
3607, such that both the step and the distal end of the collar 3606 can come
in contact with the
chassis side of the connector (not shown). In an embodiment, the collar 3606
is made from two
parts 3606A, 3606B that can be fastened together about the ferrule 3607. In an
embodiment, the
collar 3606 is made from semi-cylinders 3606A, 3606B that are fastened
together with screws
about the ferrule 3607. The cable side of the fiber optic connector also
comprises a housing
3605, which may be internally threaded. In an embodiment, the chassis side of
the connector
comprises a cylindrical opening (light output port) permitting insertion of
the area of narrower
circumference 37B up to the step, a flat contact surface, and an externally
threaded cylindrical
protrusion.
[00287] The fiber optic connector is connected by: (i) inserting the area
of narrower
circumference 37B into the cylindrical opening until the step and/or distal
end of the collar 3606
engage with the external surface of the chassis side of the connector; (ii)
sliding the housing 3605
over the collar 3606 and engaging its threading with the threading of the
chassis side of the
connector; and (iii) screwing the threading on the housing together with the
threading on the
chassis side of the connector. In an embodiment, a rear portion of the housing
3605 applies
- 94 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
pressure on the proximal end of the collar 3606 in the direction of the
chassis, and thus urges
secure contact between the collar 3606 and the chassis side of the connector
(not shown).
[00288] In an embodiment, the fiber optic connector comprises a
positioning means that
ensures the that the light path can be repeatably rotationally aligned each
time the connector is
connected. In an embodiment, the positioning means consists of a slot 3805 in
the collar 3606
and a key (not shown) that inserts into the slot 3805 when the area of
narrower circumference
37B is being inserted into the cylindrical opening. In an embodiment, the
positioning means may
consist of at least one key and at least one slot, provided that if there is
more than one key and
slot, only one correct position will permit the connector to be secured. In an
embodiment, the
positioning means may consist of at least one post and at least one hole,
provided again that if
there is more than one post and hole, only one correct position will permit
the connector to be
secured. In an embodiment, the position means may consist of a contour or
shape on one side of
the connector and a complementary contour or shape on the other, such that
there is only one
correct position, and that the correct position can be manually located. The
positioning means is
intended to include all manner of positioning mechanisms that repeatable
rotatational alignment
of the fiber optic bundle. In the foregoing embodiments, as will be apparent
to one of skill in the
art, the first step of connecting the fiber optic connector may additionally
require rotating the
collar until the positioning means properly engages.
[00289] Turning now to Figure 16, the probe 102 includes an array of
ultrasound
transducer elements forming an ultrasound transducer (not shown) covered by an
acoustic lens
1605. In an embodiment the ultrasound transducer comprises an array of
piezoelectric elements
that can both transmit and receive acoustic energy. In an embodiment, at least
some of the
ultrasound transducer elements are capable of detecting ultrasound frequencies
over a wide
range. For example, ultrasound transducer elements may be capable of detecting
ultrasound in
the range from about 50 KHz to 20 MHz. This range can be achieved by applying
a high
impedance load (e.g., in the range of 5,000 to 50,000 ohms) to achieve a lower
frequency
response. The ultrasound transducer elements are capable of generating
electrical energy in
response to receiving ultrasound acoustic energy. The electrical energy
generated by the
ultrasound transducer elements receiving ultrasound is transmitted to the
computing subsystem
128 via electrical path 108.
[00290] The probe 102 also includes one or more optical windows 1603
through which the
light carried on optical path 132 can be transmitted to the surface of a three-
dimensional volume
- 95 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
160. In an embodiment, it is desirable to locate one side of the optical
window 1603 as close as
practical to the acoustic lens 1605. The total area of an optical window 1603
is important to
maximize energy for a given fluence incident on the surface of the volume 160.
[00291] In an embodiment, the multiple strands of optical fiber making up
the optical path
132 are terminated in two light bars (not shown). In an embodiment, the
ultrasound transducer
elements (not shown) are arranged in an array that runs along a geometric
plane and are generally
spaced equidistant from each other. In an embodiment, the light bars (not
shown) are oriented
longitudinally, on each side of the planar array of ultrasound transducer
elements. Preferably the
ultrasound transducer elements generate electrical energy in response to both
ultrasound acoustic
energy received in response to stimulation caused by the pulsed light sources
130, 131 (i.e., the
optoacoustic return signal) and to ultrasound acoustic energy received in
response to acoustic
output of the ultrasound transducer elements.
[00292] Referring back to Figure 1, in use, the probe 102 may be placed in
close proximity
with organic tissue, phantom or other three-dimensional volume 160 that may
have one or more
localized inhomogenities 161, 162, such as e.g., a tumor, within. An
ultrasound gel (not shown)
or other material may be used to improve acoustic coupling between the probe
102 and the
surface of the volume 160. The probe 102, when in proximity with the surface
of the volume
160, can emit a pulse of a light through the optical windows 1603 or an
ultrasound through
acoustic lens 1605, and then generate electrical energy corresponding to
ultrasound detected in
response to the emitted light or sound.
[00293] In an embodiment, the computing subsystem 128 can trigger activity
from light
system 129 over control signal line 106. In an alternative embodiment, the
light system 129 can
create the trigger signal and inform the computing subsystem 128 of its
activity over control
signal line 106. Such information can be used to by the computing subsystem
128 to begin the
data acquisition process. In this respect, it is noted that communication over
control signal line
106 can flow both ways between the computing subsystem 128 (and/or the
optoacoustic
processing and overlay system 140 therein) and the light system 129.
[00294] In an embodiment, computing subsystem 128 can utilize control
signal line 106 to
control the start time and duration of light pulses from each light source
130, 131. The
computing subsystem 128 can also trigger the probe 102 to emit ultrasound
acoustic energy via
the ultrasound transducer elements behind the acoustic lens 1605.
- 96 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00295] In an embodiment, the computing subsystem 128 receives electrical
signals
representative of the ultrasound detected by the ultrasound transducer
elements, in response to an
ultrasound transmitted signal or an optically generated ultrasound signal,
behind the acoustic lens
1605 via electrical path 108. In an embodiment, the electrical signal
representative of the
ultrasound detected by the ultrasound transducer elements behind the acoustic
lens 1605 is the
analog electrical signal created by the elements themselves. In such
embodiment, the electrical
signals representative of the ultrasound detected by the ultrasound transducer
elements behind the
acoustic lens 1605 is transmitted to the computing subsystem via electrical
path 108, and
electrical path 108 is selectively directed by relay system 110 to the
optoacoustic processing and
overlay system 140 or the ultrasound instrument 150 for processing of the
detected ultrasound.
In such embodiment, the ultrasound instrument 150 can receive the same input
(over the same
connector) as it would receive from an ultrasound probe.
[00296] In another embodiment, the electrical signal representative of the
ultrasound
detected by the ultrasound transducer elements behind the acoustic lens 1605
is digitized by an
analog-to-digital converter which can be housed in the probe 102. In such
embodiment, time-
resolved electrical signal representative of the ultrasound detected by the
ultrasound transducer
elements behind the acoustic lens 1605 is transmitted across the electrical
path 108. Where the
electrical signal is digitized at the probe 102, as will be apparent to one of
skill in the art, the
relay system 110 may be implemented to deliver digital data to the
optoacoustic processing and
overlay system 140 or the ultrasound instrument 150, or may not be needed at
all.
[00297] The signal representative of the ultrasound detected by each of
the plurality of
ultrasound transducer elements behind the acoustic lens 1605 may be carried on
a separate wire
over the electrical path 108. Alternatively, the signal representative of the
ultrasound detected by
a plurality of ultrasound transducer elements behind the acoustic lens 1605,
or even all of the
ultrasound transducer elements behind the acoustic lens 1605, may be
multiplexed (e.g., time
division or frequency division) utilizing a multiplexer in the probe and a
demultiplexer in the
computing subsystem 128.
[00298] In an embodiment, the ultrasound instrument 150 processes
ultrasound-induced
acoustic signals to produce ultrasound images and the optoacoustic processing
and overlay
system 140 processes light-induced acoustic signals to produce optoacoustic
images. In an
embodiment, the ultrasound instrument 150 and optoacoustic processing and
overlay system 140
can be combined into an integrated system performing the combined functions of
both. As
- 97 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
discussed above, in an embodiment, electrical signals representative of
ultrasound detected by the
probe 102 and delivered to the computing subsystem 128 via electrical path 108
is switched
between the ultrasound instrument 150 and the optoacoustic instrument 140 via
relay system 110
in accordance with whether the signal results from ultrasound stimulation or
light stimulation.
[00299] In an embodiment, tomographic images reflecting the ultrasound-
stimulated data
may be generated by the ultrasound instrument 150 and tomographic images
reflecting the light-
stimulated data may be generated by the optoacoustic processing and overlay
system 140.
[00300] Images, including tomographic images, produced by the optoacoustic
processing
and overlay system 140 can be stored in a computer memory in that system,
along with data
associated with sequence or time and date of the image data that was captured.
Images, including
tomographic images, produced by the ultrasound instrument 150 may be
transmitted to the
optoacoustic processing and overlay system 140 via a suitable interface 170,
where they can be
stored, along with images generated from the light-stimulated data, in a time-
synchronized
manner. In an embodiment, images stored in the memory of the optoacoustic
processing and
overlay system 140 can be recorded to another memory, e.g., a non-volatile
memory internal to,
or external to, the device.
[00301] In an embodiment, the optoacoustic processing and overlay system
140 can
overlay images produced by the ultrasound instrument with images produced by
optoacoustic
instrument 140 for storage in the memory and/or display on one or more
monitors 112, 114. In
an embodiment, the overlayed optoacoustic image may be shown in a distinct
color to distinguish
it from the ultrasound image. In an embodiment, the overlaid optoacoustic
image may contain
colors that correspond to details discernable through optoacoustic imaging,
such as, for example,
blood oxygenation. In an embodiment, oxygenated blood is shown more in red
than blue, while
deoxygenated blood is shown in more blue than red. As used herein, the
expression overlaid
includes merging of the image by mixing as well as traditional overlaying of
the image.
[00302] In an embodiment, the device 100 may be configured to operate in a
cycle
comprising a sequence of successively generating and acquiring data relating
to one of the
device's modalities, i.e., ultrasound or optoacoustic. The minimum time
spacing between
operation of the device's modalities depends on the device 100 components and
their ability to
fully execute and recycle for use. In an embodiment, a user can select between
a variety of
preprogrammed cycles such as, for example: ultrasound only; wavelength one
only; wavelength
two only; wavelength one and two (which may be caused, e.g., by separate
lasers, or by a single,
- 98 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
quickly tunable, laser); multiple iterations of wavelength one and two
followed by ultrasound;
and/or multiple iterations of ultrasound followed by wavelength one and/or
two. Other and
further combinations will be apparent to one of skill in the art. Moreover,
where the device 100
is capable of generating more than two wavelengths, numerous additional
preprogrammed cycles
may be desirable. In an embodiment, additional cycles can be added by the
machine operator. In
an embodiment, the data collection of an entire cycle is generally intended to
be directed to
substantially the same portion of volume 160 and to be accomplished in rapid
succession. In an
embodiment, the device 100 cycles are normally in the range of 1 to 50 per
second, and more
typically in the range of 2 to 20 per second, as discussed above. The maximum
cycle frequency
is limited only by the capabilities of the cycle and modalities.
[00303] In an embodiment, the displays 112, 114 of device 100 can be
configured to show
various information depending upon the selected operating cycles. In an
embodiment, any
display 112, 144 or portion of the display can show at least one of the
following: an ultrasound
only image; a first wavelength response only image; a second wavelength
response only image; a
combined first and second wavelength response image; and/or an overlay
ultrasound image and a
wavelength response or combined wavelength response image. The combined first
and second
wavelength image may comprise a differential or other combinatorial means to
provide the
image. In an embodiment, an image can be displayed corresponding to each of
the separate data
collections in a cycle, or corresponding to the sum or difference between any
or all of them.
[00304] In an embodiment, the device can be operated using a three-phase
data collection
operation, one phase generating and collecting data in response to ultrasound
stimulus, one phase
generating and collecting data in response to a first wavelength of light, and
one phase generating
and collecting data in response to a second wavelength of light. In an
embodiment having a light
source capable of generating more than two wavelengths, the device can be
operated using a
multi-phase data collection operation, one phase generating and collecting
data in response to
ultrasound stimulus, and one phase generating and collecting data in response
to each wavelength
of light. Other and further combinations will be apparent to one of skill in
the art.
[00305] Using proper wavelength(s), optoacoustics is effective in
identifying blood within
a volume 160, and using multiple wavelengths can be used to readily
distinguish between
oxygenated and deoxygenated blood. Similarly, using proper wavelengths,
optoacoustics is
effective for measuring localized hemoglobin content within a volume 160.
Thus, for example, a
malignant tumor, which is characterized by increased blood concentration and
decreased
- 99 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
oxygenation, will appear very differently in an optoacoustic image than a
benign growth, which
is not characterized by such an increased blood concentration and has more
normal oxygenation.
Moreover, specific wavelengths of light can be selected to better distinguish
between various
biological tissues and organs. While a large spectrum of infrared, near-
infrared and visible
wavelengths can produce optoacoustic response in biological entities,
oxygenated blood is more
optoacoustically responsive than deoxygenated blood to a light source having a
wavelength of
about 1064 nm, while deoxygenated blood is more optoacoustically responsive
than oxygenated
blood to a light source having a wavelength of about 757 nm. The number and
specific
wavelength(s) of light used in the device 100 are selected in accordance with
the makeup of the
volume and the type of target that is of interest.
[00306] In an embodiment employing an ND:Yag laser to emit a pulse of
light having a
predominant wavelength of about 1064 nm and employing an Alexandrite laser to
emit a pulse of
light having a predominant wavelength of about 575 nm, the ND:Yag laser will
be pulsed first,
followed by a delay of about 50 milliseconds, followed by the pulsing of the
Alexandrite laser.
The cycle length before the following pulse of the ND:Yag laser may be 100
milliseconds or
more. Thus, in an embodiment, the pulses/delays may be as follows: ND:Yag
pulse, 50
millisecond delay, Alexandrite pulse, 50 millisecond delay, yielding a
frequency of about 10 Hz,
and a cycle time of about 100 milliseconds. Generally, regardless of the total
cycle time, the time
between the first and second light events should be as short as reasonably
practical. Thus, in
another embodiment, the pulses/delays may be as follows: ND:Yag pulse, 50
millisecond delay,
Alexandrite pulse, 150 millisecond delay, yielding a frequency of about 5 Hz,
and a cycle time of
about 200 milliseconds. In yet another embodiment, the pulses/delays may be as
follows:
ND:Yag pulse, 50 millisecond delay, Alexandrite pulse, 250 millisecond delay,
or a 450
millisecond delay, or a 950 millisecond delay, yielding, respectively, a
frequency of about 3.33, 2
and 1 Hz, and cycle times of about 300, 500 and 1,000 milliseconds. In an
embodiment, the
Alexandrite laser may be pulsed before the ND:Yag. In an embodiment, a
graphical user
interface (GUI) is provided for operating a clinical optoacoustic system, the
GUI including,
without limitation: controls that permit operator selection of the cycle time
and/or the order of
light source pulsing.
[00307] Figure 17 shows an exploded view of an embodiment of the probe 102
shown in
Figure 16. Shells 1702, 1704 are separated to show the components within the
probe 102. The
shells 1702, 1704 may be made from plastic or any other suitable material. The
surfaces of the
- 100 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
shells 1702, 1704 that may be exposed to light, and especially light generated
by the light
subsystem 129, are preferably both reflective (i.e., light colored) material
and light scattering
(i.e., having a scattering coefficient between 1 and 10). In an embodiment,
the surfaces of the
shells 1702, 1704 are highly reflective, i.e., more than 75% reflective. In an
embodiment, the
surfaces of the shells 1702, 1704 are very highly reflective, i.e., more than
about 90% reflective.
In an embodiment, the surfaces of the shells 1702, 1704 have low optical
absorption, i.e., less
than 25% absorptive. In an embodiment, the surfaces of the shells 1702, 1704
have very low
optical absorption, i.e., less than about 10% absorptive. In addition, the
material forming the
shells 1702, 1704 should be acoustically absorbent to absorb, rather than
reflect or transmit
acoustic energy. In an embodiment, white plastic shells 1702, 1704 are used.
[00308] In an embodiment, flex circuit 1712 comprises a plurality of
electrical traces (not
shown) connecting cable connectors 1714 to an array of piezoelectric
ultrasound transducer
elements (not shown) forming ultrasound transducer 1710. In an embodiment,
flex circuit 1712
is folded and wrapped around a backing 1711, and may be secured thereto using
a bonding agent
such as silicon. In an embodiment, a block 1713 is affixed to the backing 1711
opposite the array
of piezoelectric ultrasound transducer elements. In an embodiment, the
ultrasound transducer
1710 comprises at least 128 transducer elements, although it may be desirable
to have a greater
number of transducer elements, as additional elements may reduce distortion,
and/or increase
resolution, accuracy and/or depth of imaging of the device 100. The cable
connectors 1714
operatively connect the electrical traces, and thus, the ultrasound transducer
1710, to the
electrical path 108. In an embodiment, the electrical path 108 includes a
coaxial wire for each
ultrasound transducer element in the ultrasound transducer array 1710.
[00309] The ultrasound transducer 1710 fits within housing 1716 so that
the transducer
elements are in close proximity to, or in contact with an acoustic lens 1605.
The acoustic lens
1605 may comprise a silicon rubber, such as a room temperature vulcanization
(RTV) silicon
rubber. In an embodiment, the housing 1716 and the acoustic lens 1605 are
formed as a single
unit, from the same RTV silicon rubber material. In an embodiment, the
ultrasound transducer
1710, portions of the flex circuit 1712, backing 1711 and block 1713 are
secured within the
housing 1716 including an acoustic lens 1605 using a suitable adhesive such as
silicon to form a
transducer assembly 1715. The block 1713 can be used to affix or secure the
transducer
assembly 1715 to other components.
- 101 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00310] To whiten, and reduce the optoacoustic effect of light generated
by the light
subsystem 129 on an RTV silicon rubber acoustic lens 1605 and/or the
transducer assembly
1715, in an embodiment, the RTV silicon rubber forming the acoustic lens 1605
and/or the
transducer assembly 1715 may be doped with Ti02. In an embodiment, the RTV
silicon rubber
forming the acoustic lens 1605 and/or the transducer assembly 1715 may be
doped with
approximately 4% Ti02. In an embodiment, the outer surface of the acoustic
lens 1605 and/or
the outer surface of the transducer assembly 1715 may additionally be, or
alternatively be, coated
with a thin layer of metal such as brass, aluminum, copper or gold. Gold,
however, has been
found to have a tendency to flake or crack off of RTV silicon rubber. In an
embodiment, the
RTV silicon may be first coated with perylene, then coated with nickel, then
coated with gold,
and finally, again, coated with perylene. In an embodiment, the RTV silicon
may be first coated
with nickel, then coated with perylene, then coated with gold, and finally,
again, coated with
perylene. In an embodiment, the outermost coating of perylene may be omitted.
The multiple
layering provides a durable gold coating without any substantial adverse
effect to the acoustic
properties of the acoustic lens 1605, and without any substantial adverse
effect to the transducer
assembly 1715 to detect ultrasound. In practice, it has been found that the
perylene coatings
adjacent to the nickel and the gold layers, may curl at the edges rather than
adhering well to the
metals or rubber upon which it is deposited. Thus, as discussed in more detail
below, in an
embodiment, the portions of the acoustic lens 1603 and/or transducer assembly
1715 having an
edge capable of being mechanically secured against other components to prevent
curling or
peeling. In an embodiment, substantially the entire outer surface of the
transducer assembly
1715, including the acoustic lens 1605, are coated with continuous layers of
nickel, then
perylene, then gold and then perylene again.
[00311] In an embodiment, a reflective material surrounds the transducer
assembly 1715
from the rear edge of the housing 1716 to the end of the flex circuit 1712 to
reflect any light from
the light path 132 that may be incident upon its surfaces. In an embodiment,
an electromagnetic
shield for RF energy surrounds the transducer assembly 1715 from the rear edge
of the housing
1716 to the end of the flex circuit 1712. In an embodiment, the lights 130,
131, may draw
substantial energy (e.g., more than 1,000 volts for a few nanoseconds)
creating substantial
electromagnetic RF energy in the area of the probe 102. In an embodiment, the
transducer
assembly 1715 from the rear edge of the housing 1716 to the end of the flex
circuit 1712 is
surrounded by a foil, which may act as a reflective material and an RF energy
shield. In an
- 102 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
embodiment, the foil is selected from the group: copper, gold, silver. In an
embodiment, the foil
is tied into the device's 100 electrical ground.
[00312] Spacers 1720 space and position the light bar guide 1722 with
respect to the
transducer assembly 1715. Spacers are preferably made from materials that
reduce its
optoacoustic response to light generated by the light subsystem 129. In an
embodiment, the
spacers 1720 are made from a material similar to the light contacting portions
of the shells 1702,
1704. In an embodiment, the light bar guide 1722 encases optical fibers that
are part of the light
path 132. In an embodiment, the optical fibers making up the light path 132
may be randomly
(or pseudo-randomly) distributed throughout the light bar guide 1722, thus
making specific
locations on the light receiving end of the fiber optic bundle at least pseudo-
random with respect
to corresponding specific locations on the light emitting end of the optical
fibers retained by the
light bar guide 1722. As used herein the term randomly (or pseudo-randomly)
distributed optical
fibers making up the light path 132 means that the mapping of fibers from the
proximal end to
the distal end is done such that a localized interference in the light path
132 (e.g., burnout of a
group of adjacent optical fibers) or a localized phenomenon (e.g., non-uniform
light at the entry
point to the optical path 132) will have an effect on the overall power
transmitted, but will not
have an operationally significant effect on any specific part of the distal
end of the light path 132.
Thus, two optical fibers adjacent at the proximal end are unlikely to be
adjacent at the distal end
of the optical path 132. Where optical fiber bundles are fused at the proximal
and distal ends, the
randomization must be done before at least one end is fused. As used herein
the term randomly
(or pseudo-randomly) distributed optical fibers does not mean that two
different optical paths 132
¨ i.e., for different devices 100 ¨ must differ from each other. In other
words, a single "random"
mapping may be reproduced in the light path of different devices 100 while
still meeting the
criteria of being a randomized. Because light generally behaves in a Gaussian
manner, the entry
point to the light path 132 is typically less than perfectly uniform.
Randomization, as discussed
above, may accommodate for the non-uniform entry of light into the light path
132.
Randomization may also provide homogenization of light fluence over area
illuminated, as it
may aid in more evenly distributing the light fluence.
[00313] In an embodiment, the optical fibers encased by a light bar guide
1722 all end on
substantially the same geometric surface, e.g., a curved or flat plane. In an
embodiment, the
fibers at the distal end, within a given light bar, may be grouped and
subgrouped in a manner that
may help hold the fibers in position during manufacturing. Such grouping (such
as in groups for
- 103 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
the two light bars) and subgroupings (e.g., having subgroups per lightbar) may
further the even
distributing over the geometric surface. Any number of subgroups may be used.
In an
embodiment, the number of subgroups is selected to be practical for
fabrication and
manufacturing. In an embodiment, the number of subgroups is selected to
facilitate the
manufacturing process. In an embodiment, the number of subgroups may be
between 5 and 20,
and may be 15. In an embodiment, the fiber groups are formed by placing fiber
subgroups
between physical channels that are molded or machined into light bar guide
1722, or its internal
and/or external surfaces.
[00314] In one embodiment, after the fibers have been attached to the
light bar guide 1722,
the fiber ends may be lapped and polished to provide for a more uniform angle
of light emission.
In an embodiment, the light bar guide 1722, as installed in the assembled
probe 102, directs the
light emitting there-from at an angle slightly less than normal to the distal
face of the probe 102,
and specifically, at small angle inwards, towards the plane normal to and
intersecting the center
of the acoustic transducer array 1710. In an embodiment, the distal end(s) of
the optical path 132
should match ¨ or closely approximate the shape of the acoustic transducer
array 132.
[00315] The term bar, as used in "light bar guide" herein is not intended
to import a
specific shape. For example, the light bar guide 1722 may guide the distal
ends of optical fibers
into substantially any shape such as, without limitation, a whole or part of a
circle, oval, triangle,
square, rectangle or any irregular shape.
[00316] In an embodiment, one or more light bar guides 1722 and optical
windows 1603
are external to the shells 1702, 1704 housing the acoustic transducer assembly
1715, and are
adapted to be attached to the outer sides of one or more of the shells 1702,
1704.
[00317] In an embodiment, the angle of light emitting from the optical
window 1603 may
be adjustable. In an embodiment, the light emitting from the optical window
1603 may be
adjustable across a range. At one end of the range, light may emit from the
optical window 1603
in a direction normal to the distal face of the probe 102, and at the other
end of the range light
may emit from the optical window 1603 at an inward angle of up to 45 degrees
or more towards
the plane normal to and intersecting the center of the acoustic transducer
array 1710. The range
can be smaller or larger. In this respect, a lower bound of the range could be
set to be not less
than 45 and a higher bound of the range could be set to be not greater than 90
degrees.
[00318] In an embodiment wherein a probe has two optical windows 1603, the
angle of
light emitting from both optical windows 1603 can be adjustable, individually,
or together.
- 104 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Where adjusting the angle of light emitting from both optical windows 1603
together, the light
direction would, in each case increase or decrease the angle of inward
projection, that is,
projection towards the plane normal to and intersecting the center of the
acoustic transducer array
1710. In this manner, a larger light fluence can be directed deeper into the
volume 160 (by
angling toward normal), or shallower (by angling more inwardly).
[00319] Controlling the direction of the light angle can be done by moving
the light bar
guide 1722, or it can be accomplished optically through the use of post-light
path 132 optics. In
this respect, the movable light bar guide and the optical window may be
provided external to the
shell housing the acoustic transducer assembly, and may be adapted to be
attached to an outer
side of the shell. A second movable light bar guide may also be operatively
connected to the
shell housing the acoustic transducer assembly of the probe, and may movably
retain the distal
end of a second set of optical fibers. The first movable light bar guide and
the second movable
light bar guide may be capable of varying the angle of light transmission of a
first set of optical
fibers and varying the angle of light transmission of the second set of
optical fibers independently
of one another. Optical solutions may include the use of one or more lenses
and/or prisms to re-
direct the light that has been transmitted through the light path 132, or by
using an optical
element having a variable index of refraction, such as, for example, an
optical element having an
index of refraction controlled in response to electric fields. Re-directed
light can be directed to
illuminate a desired area, such as an area directly beneath the transducer
elements 1710.
Controlling the direction of light transmitted by the probe 102 is useful to
maintain safe and
optimize the direction of the light with respect to the skin and the
transducers.
[00320] Control line 109 may be used to send commands redirecting light
and/or to report
the actual direction of light at the time a light pulse is emitted from the
light path 132. The angle
of the light emitting from the optical window 1603 may be important data to
consider when
interpreting acoustic information resulting from the light pulse. In
embodiment that include a
second movable light bar guide and second set of fibers, such light bar guide
may be capable of
varying the angle of light transmission of the second set of optical fibers in
response to at least a
second command.
[00321] In an embodiment, the device 100 can adjust the angle of incident
laser light
emitting from the probe 102. Adjustment of the angle of incident laser light
emitting from the
probe 102 may be carried out under the control of commands which may be sent
via control line
109, or may be manually carried out, e.g., by an adjustment mechanism located
on the probe. In
- 105 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
an embodiment, a standoff may be used, e.g., to help direct incident laser
light to the desired
depth, or closer to the surface than can be achieved without a standoff In an
embodiment, the
standoff is relatively transparent to both acoustic and light, and preferably
to acoustics in the
ultrasound range and light one or more of the wavelengths utilized by the
light source 129.
While the use of standoffs is known in ultrasound applications to aid in
imaging of objects close
to the surface of the volume 160 because ultrasound resolution lacks the
capability to detect
objects at a nominal distance from its transducers, the use of a standoff in
the present application
is for a different purpose, namely, to allow the light sources to be aimed
directly under the
transducer elements 1710. In an embodiment, the standoff is separate from the
probe 102, and
placed between the volume 160, and the distal end of the probe 102 comprising
the acoustic lens
1605 and one or more optical windows 1603. In an embodiment, the standoff may
be integral to
the probe, and may be move into place and withdrawn as desired.
[00322] Optical windows 1603 may also be part of the probe 102 assembly.
In an
embodiment, the optical windows 1603 is spaced from the end of the light bar
guide 1722, and
thus, from the ends of the optical fibers making up the light path 132. The
term optical window,
as used here, is not limited to mechanically or optically flat optical matter,
or solely to
transparent optical matter. Instead, the term is used to refer to an optical
element that may or
may not effect light passing there-through, but will permit at least a
substantial portion of the
light incident on the side of the window proximal to the light path 132 to
exit the probe assembly
102 in a manner that is dependent on the properties of the optical element. In
an embodiment,
the optical window 1603 may be transparent, which permits transmission of
light, and
specifically light emitted from the end of the light path 132, to volume 160
when the distal end of
the probe 102 is in contact with or close proximity to that volume 160. In an
embodiment, the
optical window 1603 may be translucent, permitting diffusion and transmission
of light, and
specifically light emitted from the end of the light path 132, to volume 160
when the distal end of
the probe 102 is in contact with or close proximity to that volume 160. In an
embodiment, the
optical window 1603 may be a lens, permitting the shaping and directing of
light, and
specifically light emitted from the end of the light path 132, to volume 160
when the distal end of
the probe 102 is in contact with or close proximity to that volume 160.
[00323] In the assembled probe 102, one edge of the optical window 1603 is
in close
proximity to, or in contact with, the transducer assembly 1715. The proximity
of the optical
window 1603 to the transducer assembly 1715 allows light emitted from the
optical window
- 106 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
1603 to be emitted from a location close to the acoustic lens 1605, and thus
close to the plane of
the transducer array 1710.
[00324] In use, a coupling agent (e.g., gel) may be used to improve the
acoustic contact
between the distal end of probe 102 and the volume 160. If the coupling agent
makes contact
with the distal end of the optical fibers forming the light path 132,
extraneous acoustic signal
may be generated in response to light transmission over the light path 132. In
an embodiment,
the distal end of the probe 102, including optical window 1603, mitigates the
potential acoustic
effect of a coupling agent in response to light emitting from the light path
132 by creating a gap
between the coupling agent and the distal end of the optical fibers.
[00325] Figure 18 shows a cutaway view taken along the centerline of the
wider face of
one embodiment of an assembled probe 102 such as the probe shown in Figure 16.
Shells 1702,
1704 support optical windows 1603 and transducer assembly 1715 at the distal
end of the probe
102. Spacers 1720 supported by transducer assembly 1715 and shells 1702, 1704
aid in the
positioning of optical widows 1603 and light bar guides 1722, and in
maintaining gap 1802
between light bar guides 1722 and the optical windows 1603.
[00326] The distal ends of the optical fibers making up the light path 132
may be
positioned such that they do not create a physical sound conduction path to
the volume 160 or to
the acoustic transducers 1710. In an embodiment, the gap 1802 serves the
purpose of preventing
high frequency sound conduction path between the distal ends of the optical
fibers making up the
light path 132 and the volume 160 or the acoustic transducers 1710. Specially
selected materials,
as discussed below, can be used to ensure that the light bar guide 1722
reduces and/or minimizes
the physical sound conduction path between the distal end of the light path
132 and the volume
160 or the acoustic transducers 1710.
[00327] Flex circuit 1712, with piezoelectric transducer elements (not
shown) thereon,
wraps around backing 1711, and electrically connects the piezoelectric
transducer elements with
the cable connectors 1714 at each end of the flex circuit.
[00328] Opening 1804 in the shells 1702, 1704 provides an opening for
optical path 132
(Figure 1), electrical path 108 (Figure 1) and optional power and control
lines 109 (Figure 1) to
enter the inside of the probe 102. In an embodiment, a rubber grommet (not
shown) may be used
to provide stability and strain relief to the paths or lines passing into the
probe 102 through
opening 1804.
- 107 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00329] Referring briefly to Figures 34 and 35, a probe holder 3400 is
shown. The novel
probe holder 3400 differs from a more typical probe face-up design that is
used for an ultrasound
probe. In an embodiment, the probe holder comprises a wire support 3405 and a
probe support
3406, a rear wall 3408 with screw holes 3407 for securing the probe holder to
a cart or other
component of an optoacoustic system. The probe-end enclosing portion of the
probe holder 3400
operates to encircle the active (distal) end of the probe 102. In an
embodiment, the probe-end
enclosing portion of the probe holder 3400 is made of materials that are
substantially opaque to
the light emanating from the light subsystem 129, thus reducing the risk of
laser light leakage
when the probe is in the probe holder. Moreover, in an embodiment, the probe-
end enclosing
portion of the probe holder 3400 is designed to provide a snug fit with the
outer walls of the
probe housing, again reducing the risk of laser light leakage when the probe
is in the probe
holder.
[00330] As is apparent from the figures, probe support 3406 both supports
the probe in a
position that it can be easily removed manually ¨ by spacing it from the probe
holder bottom
3410 ¨ but also is positioned behind the housing in such a manner as to
inhibit the probe from
sliding backwards and out of the probe holder 3400. In an embodiment, probe
support 3406 may
be used to support the probe 102 by its strain relief collar 3420. The wire
guide 3405 is spaced
from the probe support 3406 to reduce the pressure on the probe's 102 strain
relief collar 3420
and soften the angle of curvature of the light path 132 and the integrated
electrical path 108/109.
In an embodiment, the probe holder will hold the probe 102 at an angle that is
greater than
parallel with the floor. In an embodiment, when seated in the probe holder
3400, the probe 102
will be maintained at an angle between 10 and 45 degrees with respect to
horizontal.
[00331] On the interior distal end of the probe-end enclosing portion of
the probe holder
3400, the distal end of the probe 102 may be supported from the probe's
housing 1702/1704. In
an embodiment, the design permits the probe to be securely positioned in a
manner that the distal
end of the probe's housing 1702/1704 (i.e., adjacent to the optical window
1603) may be in
contact with the interior distal end of the probe-end enclosing portion of the
probe holder 3400,
but the optical windows 1603, acoustic lens 1605, and any other delicate or
operational
components at the active end of the probe 102 are either not in contact with
the probe holder
3400, or in minimal contact therewith. In an embodiment, the interior distal
end of the probe-end
enclosing portion of the probe holder 3400 comprises a recess to permit secure
seating of the
probe 102 therein without contact between it and delicate probe components.
Screw holes 3407
- 108 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
are provided to permit secure attachment of the probe holder 3400 to an
appropriate location. In
an embodiment, the probe holder 3400 can be securely fastened to a cart 3200.
In an
embodiment, a probe holder can be designed to be integral to a cart 3200, and
need not be
external thereto.
[00332] In an embodiment, a probe holder includes a sensor (e.g., a
pressure sensor) to
detect the presence of the properly-seated probe. Where such a sensor is
employed, the output of
the sensor can be used, for example, by the optoacoustic processing and
overlay system 140 to
override laser firing. In such an embodiment, this override can be alternative
to, or in addition to
forming the probe-end enclosing portion of the probe holder from materials
that are substantially
opaque to the light emitted from the optical window(s) of the probe.
Alternatively, in an
embodiment, the probe-end enclosing portion of the probe holder may maintain
the active end of
a properly inserted probe a short distance from an energy or power meter
capable of measuring or
inferring the total power or energy of the light emitting from the probe for
calibration,
maintenance or other purposes. In such an embodiment, where the probe holder
also includes a
sensor, the output of the sensor can be used by system software, such as for
example, by the
optoacoustic processing and overlay system 140 to engage laser firing for
diagnostic, calibration,
maintenance or other purposes.
[00333] Turning to Figures 19A, a typical pattern of light striking a
surface in close
proximity to the ends of ten optical fibers is shown. Today, typical,
reasonably flexible optical
fibers have a diameter in the range of about 50 to 200 microns. Light exiting
an optical fiber
tends to expand slowly, see, for example, an illustrative example of light
expanding after leaving
the end of an optical fiber in Figure 19B. The rate of expansion of the light
beam leaving an
optical fiber is a function of the diameter of the optical fiber and the
refraction index of the
optical fiber material, and may also be a function of the refraction index of
the material to which
the fiber is connected. When a group of optical fibers are placed in close
proximity to a surface
to be illuminated, a light pattern like that seen in Figure 19A results.
[00334] In an embodiment, optical fibers having smaller diameters are
employed to
broaden the illuminated area and minimize weight and increase flexibility of
the light path 132.
Light diverges as it exits a fiber optic, and its divergence as it exits is
inversely related to the
diameter of the fiber ¨ in other words, light diverges faster out of smaller
diameter fiber optics.
Thus, for example, optical fibers in the range of under 50 microns, and
potentially less than 30
microns may be desirable to broaden the illuminated area, thus reducing, or
potentially
- 109 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
eliminating the need for a beam expander. In an embodiment, the distal end of
one or more
groups of the optical fibers comprising the light path 132 may be fused to
avoid the characteristic
pattern of light shown in Figure 19A.
[00335] In an embodiment, an optoacoustic probe should produce a
relatively uniform
light distribution incident upon the surface of the illuminated volume. It may
also be desirable
for an optoacoustic probe to produce a relatively large area of light
distribution. Providing a
relatively large and uniform light distribution permits an optoacoustic probe
to deliver a
maximum amount of energy without exceeding a specific light fluence on any
given area of the
illuminated surface, which can maximize patient safety and/or improve the
signal-to-noise ratio.
For these reasons, it is not desirable to locate the optical fiber ends in too
close proximity with
the surface of the illuminated volume, and thus, obtain a small or uneven
light distribution such
as the one seen in Figure 19A.
[00336] In an embodiment, the optical fibers may be moved away from the
surface of a
volume to be illuminated. Moving the end of the optical fibers away from the
surface of the
volume to be illuminated will cause the beams emitted from each optical fiber
to expand, and
produce a more uniform area of light distribution. One potential issue
associated with moving
the optical fibers away from the surface of the volume to be illuminated, is
the optoacoustic
effects caused by stray portions of the expanding beam. Another potential
issue is the effect of
enlarging the distance (between the end of the optical fibers and the surface
to be illuminated) on
the shape or size of a probe. Further, increasing the number of optical fibers
(and thus enlarging
the area of the fiber bundle emitting light) will increase the cost, weight
and flexibility of the
optical path 132 (Figure 1), and may also affect the size of the probe.
[00337] Because the probe 102 is designed to be handheld, it is desirable
to keep the probe
head (the wider, distal portion of the probe 102) short so that the probe stem
(the narrower,
proximal portion of the probe 102) is relatively close to the surface of
volume 160. Additionally,
because the probe 102 is designed to be handheld, its total thickness is also
a consideration for
comfort, convenience and operational effectiveness. Accordingly, locating the
distal ends of the
fibers forming light path 132 at a sufficient distance from the optical window
1603 to permit
expansion to fill the optical windows 1603 with uniform light fluence is not
preferred. Similarly,
using a very large number of fibers to enlarge the area of the fiber bundle
held by the light bar
guide 1722 at the distal end of the light path 132 and thereby attempting to
permit expansion to
fill the optical windows 1603 with uniform light fluence is also not preferred
as it would, among
- 110 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
other things cause undue weight, inflexibility, size and cost. Moreover,
reducing the size of the
optical window 1603 would reduce the total potential safe energy output of the
device, and thus,
is not preferred.
[00338] Turning to Figures 20B and 20C, in an embodiment, a beam expander
2001b,
2001c may be used to expand the beam of light, causing it to become more
uniform over a
shorter distance. Figure 20b shows the use of a ground or frosted glass beam
expander 2001b,
while Figure 20C shows the use of a lens beam expander 2001c. In an
embodiment, where the
light bar guide 1722 is generally rectangular, a lens beam expander 2001c may
be a cylindrical
convex lens or a cylindrical concave lens. In an embodiment, a convex lens
(not shown) may be
used as a beam expander. It will be apparent to one of skill in the art that
other lenses, lens
systems or other optical systems or combinations thereof, can be used to
spread and more evenly
distribute the light.
[00339] Referring back to Figure 18, in an embodiment, the light bar
guides 1722 are
angled inward toward the ultrasonic imaging plane on the end retaining the
distal ends of the
fibers. The inward angling of the distal end of the light bar guide 1722
permits the light emitting
there-from to better fill, and thus, evenly illuminate the optical window
1603. Gap 1802, which
may include a beam expander, may provide space for the light transmitted
across the light path
132 to expand to fill the optical window 1603. The inward angling tends to
cause the direction of
the light incident on the surface of the volume 160 to strike the surface at
an angle less than
normal, and thus, potentially, to better propagate into the volume beneath the
acoustic lens 1605
covering the ultrasound transducers 1710.
[00340] Turning back to Figure 1, because the probe 102 is intended for
handheld use, the
weight and flexibility of the light path 132, the electrical path 108 and the
optional power and
control lines 109 is of consideration. In an embodiment, to make the light
path 132 lighter and
more flexible, the light path 132 is constructed from as few fibers as
possible. A limiting factor
to how few a number of fibers that can be used, is the amount of light carried
across the optical
path 132. The transmission of too much light over a fiber will damage the
fiber. The light path
132 must carry the total amount of light that will be fluent on the surface of
the volume 160, plus
any light lost (e.g., absorbed or scattered) between the light source 129 and
the surface of the
volume 160 illuminated. Since the maximum area of illumination is known not to
exceed the
size of the optical window 1603, and because the area of illumination is
subject to fluence limits
per unit area, a total light energy carried by the light path 132 can be
approximated by
- 111 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
multiplying the fluence limit by the size of the optical windows 1603. The FDA
provides
numbers for the human safe level of fluence.
[00341] The volume 160 illuminated generally has its own optoacoustic
response, which is
especially apparent where light fluence is greatest, namely, at the surface of
the volume 160.
Increasing the area of illumination onto the surface of the volume 160 (e.g.,
by increasing the
size of the optical window 1603 and beam) reduces the optoacoustic affect
generated by the
surface of the volume 160 itself, and thus may reduce the undesirable
optoacoustic signal
generated by the surface of the volume 160 itself as compared to a desired
signal representing the
inhomogenities 161, 162.
[00342] In addition to unwanted optoacoustic signal generated by the
surface of the
volume 160 itself, there may be other sources of unwanted optoacoustic signals
that can be
detected by the ultrasound transducer, such as the side walls surrounding the
space between the
optical windows 1605 and the respective light bar guides 1722, the acoustic
lens 1605 and
portions of the transducer housing 1716. The optical windows 1603 and any
optional beam
expander 2001B, 2001C may also be sources of unwanted optoacoustic signals
that can be
detected by the ultrasound transducer.
[00343] In an embodiment, the walls surrounding the space between the
optical windows
1605 and the respective light bar guides 1722 may be made from a material that
has high acoustic
absorption properties and/or that is white and/or has high light scattering
and/or reflecting
properties. Using materials having these characteristics may reduce unwanted
optoacoustic
signals that can be detected by the ultrasound transducer. In an embodiment,
the spacers 1722
can be made from a resin material such as Micro-Mark CR-600, a two part high
performance
casting resin that dries to a white color.
[00344] In an embodiment, a layer (not shown) of material that has high
acoustic
absorption properties and/or that is white and/or has high light scattering
properties is placed
between the transducer assembly 1715 and the light bar guides 1722 in the
assembled probe 102.
Alternatively, the layer may be applied directly to the transducer assembly
1715 or the light bar
guide 1722 where the two parts contact in the assembled probe 102. This layer
may reduce
unwanted optoacoustic signals that can be detected by the ultrasound
transducer. In an
embodiment, the layer can be made from a resin material such as Micro-Mark CR-
600, a two part
high performance casting resin that dries to a white color. In an embodiment,
the layer (not
- 112 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
shown) may also comprise a reflective coating. In an embodiment a reflective
coating of gold is
applied to the layer to reflect light that might otherwise strike the layer.
[00345] In an embodiment, anti-reflective coatings may be used to reduce
the optoacoustic
signature of the optical window 1603 and/or the beam expander 2001B, 2001C. In
an
embodiment, magnesium fluoride may be used as an anti-reflective coating on
the optical
window 1603 and/or the beam expander 2001B, 2001C. Anti-reflective coatings
may be used to
reduce and/or minimize energy absorbed or reflected by the optical window
1603.
[00346] In an embodiment, the optoacoustic signature of the transducer
assembly 1715
and/or acoustic lens 1605 can be reduced by whitening. In an embodiment, an
acoustic lens 1605
comprising RTV silicon rubber may be whitened and have its optoacoustic
signature reduced by
being doped with about 4% Ti02. It is believed that the TiO2 doping increases
the reflectivity of
the acoustic lens and therefore the absorption, and also has a scattering
effect that tends to diffuse
the optoacoustic response of the RTV silicon rubber, bringing the response
down to a lower
frequency which can be more easily filtered. As discussed above, the outer
surface of the
transducer assembly 1715 and/or acoustic lens 1605 may be given a metal
coating, such as gold,
copper, aluminum or brass. In an embodiment, the metal coating, and in
particular, gold, reduces
the optoacoustic signature of the transducer assembly 1715 and/or acoustic
lens 1605. It is
believed that gold reduces the optoacoustic signature of the acoustic lens
1605 because of its high
reflectivity in the light spectrum. In an embodiment, the acoustic lens may
not be whitened and
may retain its natural color, or be colored differently to minimize optical
absorption at one or
more particular wavelengths. In an embodiment, the acoustic lens may be made
of materials
other than RTV silicon rubber, such as, for example, buna-N rubber (i.e.,
nitrile rubber) or latex
rubber.
[00347] As discussed above, the optical fibers at the end of the optical
path 132 are
retained by the light bar guide 1722 with all of the fiber ends retained by
the light bar guide 1722
located on substantially the same plane. In an embodiment, the fiber ends may
be fixed in place
using mechanical force, an adhesive, or a combination of mechanical force and
an adhesive. The
fibers may be glued near their distal end to keep them in the desired location
and pattern, and/or
to reduce output of mechanical energy due to laser firing. In an embodiment,
the spaces between
optical fibers fixed within the light bar guide 1722 may be filled with a
material having one or
more of the following characteristics: sound absorbing, light scattering,
white and/or light
reflecting. In an embodiment, the optical fibers, which may be encased by a
light bar guide 1722
- 113 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
at the distal end of the light path 132 are fused. Fusing fibers at the distal
end of the light path
132 may permit the light emitting from the light path to be more uniform.
[00348] In an embodiment, a reflective coating is placed on areas of the
shells 1702, 1704
where laser light emanating from the optical path 132 may strike it, including
with the assembled
probe, and in the areas designed to make skin contact, e.g., near the optical
window 1603 and
other portions of the distal end of the probe 102. In an embodiment, the
shells 1702, 1704 are
coated in gold where laser light emanating from the optical path 132 may, or
is likely to strike it.
In an embodiment, portions of the shell 1702, 1704 may be made from gold,
although at present
this may be cost prohibitive.
[00349] In an embodiment, a proximity detector system (not shown) is used
to determine
that the distal end of the probe 102 is on or very near the surface of a
volume. Among the
reasons such a proximity detector system is desirable is that it can be used
to prevent pulsing of
the light source 129 when the probe 102 is not in close proximity to a volume
160 under
inspection, or to be inspected. This may be a safety issue as the light source
129 may produce
light at levels that can be harmful, e.g., to the eyes. The proximity detector
system may be
implemented in the form of: a mechanical contact switch at the distal end of
the probe; an optical
switch looking at reflections of a non-harmful beam from the surface of the
volume 160; a
conductive switch that is closed by contact with the volume 160 and/or any
acoustic gel or other
materials between the volume 160 and the distal end of the probe; a conductive
switch and a
standoff comprising a conductive surface for contact with the distal end of
the probe 102; a
conductive switch and a thin, optically and acoustically transparent,
conductive surface applied to
the surface of the volume 160 of interest; an acoustic transducer switch that
can detect close
proximity of the volume 160 by transmitting and looking for the reflection of
a sound within a
specific time; an acoustic transducer switch that can detect close proximity
of the volume 160 by
using a narrow shape sound transmitter and receiver and using the reflection
to detect proximity;
using one or more of the transducers in the transducer array as a proximity
detector by looking
for a signal return; or by operating the device 100 in an ultrasound mode and
looking for an
ultrasound image.
[00350] In an embodiment, an optical detector (not shown) may be located
in the probe
102 to take a measurement from which output energy can be estimated or
deduced. In an
embodiment, the optical detector will measure reflected energy such as energy
reflected by the
beam expander or optical window. In an embodiment, the optical detector will
measure scattered
- 114 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
energy such as energy scattered by the materials surrounding the gap 1802. The
measurement of
the optical detector can be transmitted to the system chassis 101 via control
signal line 109,
where it can be analyzed to deduce or estimate the light output of the probe
102. In an
embodiment, control functionality in the system chassis 101 can control or
regulate the light
output of the light system 129, and thus the light output of the probe 102
based on a measurement
made by the optical detector. In an embodiment, control functionality in the
system chassis 101
can control or regulate the gain in the transducer receivers to compensate for
variation of the light
output of the probe 102 based on a measurement made by the optical detector.
In an
embodiment, the computing subsystem 128 can trigger differing activity from
light system 129
over control signal line 106 based on a measurement made by the optical
detector. In an
embodiment, a measurement made by the optical detector can be used to control
for variations in
the electrical system or the power to the device 101. Similarly, in an
embodiment, a
measurement made by the optical detector can be used to control for variations
in the optical path
132 or other optical elements of the device 100. In an embodiment, the optical
detector can be
used to cause the fluence of light output by the probe 102 to remain close to,
but below, safe
limits by accommodating for variations in electrical or optical
characteristics that might
otherwise cause the fluence of light output by the probe 102 to exceed or fall
far below the safe
limit.
[00351] In an embodiment, a safety feature would prevent disconnection of
the probe 102
from the flexible cable when the system is in operation (e.g. when the laser
is firing). To
implement this safety feature, in an embodiment, the system 100 can use
control line(s) 109 to
operate a mechanical lock on the connector between the probe and the flexible
connector. In an
embodiment, a fail-secure mechanical lock would only permit disconnection of
the probe 102
from the flexible cable when a specific control line(s) 109 was at voltage
greater than a
prespecified amount.
[00352] As discussed above, the device 100 comprises a probe 102 that, in
an
embodiment, is capable of transmitting both ultrasound and light to a volume
160, and is capable
of receiving and processing an ultrasonic response to the transmitted
ultrasound and light. The
ultrasonic response to the transmitted ultrasound is typically a narrow
bandwidth around the
transmit frequency, with a percent bandwidth of about 70% and having no
meaningful response
below 2Mhz, while the ultrasonic response to transmitted light is typically in
a much broader
range, such as the range of about 50 KHz to 20 MHz or more, typically centered
in the range of 6
- 115 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
MHz to 8 MHz. In an embodiment, ultrasound is transmitted and received by the
transducers
1710, while light is transmitted by a light 130, 131, across the optical path
132, and across the
optical window 1603 or other aperture, the ultrasonic response thereto is
received by separate
transducers (not shown) tuned to receive the higher frequency range typically
generated by the
optoacoustic effect. The separate transducers are operated with high impedance
amplifiers, e.g.,
having an impedance of more than 200 ohms, and preferably being about 500 ohms
or more.
Where the optoacoustic response is received by separate transducers, or by the
same transducers
using differing impedance loads from their use for ultrasound response, the
signals representing
the ultrasound response may be carried back to the system chassis 101 on
separate wires of the
electrical path 108 from the signals representing optoacoustic response.
[00353] In an embodiment, ultrasound is transmitted by the transducers
1710, and the
ultrasonic response thereto is received by the transducers 1710, and light is
transmitted by a light
130, 131, across the optical path 132, and out the optical window 1603, and
the ultrasonic
response thereto is also received by the transducers 1710. In such embodiment,
the transducers
1710 are operated with high impedance amplifiers having an impedance of more
than 1K ohm
and less than about 100K ohms, and more preferably between 2K and 10K ohms
input
impedance. In an illustrative embodiment, the transducers 1710 may be operated
with a 5K
ohms input impedance amplifier.
[00354] In an embodiment where the probe 102 is equipped with ultrasound
transducers
1710 and separate transducers (not shown) tuned to receive the higher (vs.
broader) frequency
range typically generated by the optoacoustic effect, the optoacoustic
response for light that
transmitted by a light 130, 131, across the optical path 132, and out the
optical window 1603,
may be received by both the transducers 1710 and by the separate transducers.
Using both sets of
transducers to receive ultrasound responsive to the optoacoustic effect may
capture additional
data that can be used to better analyze target 161, 162 within a volume 160.
[00355] Turning to Figures 21-23, phantoms formed from plastisol are
useful for
registration and calibration. Figure 21 shows a phantom 2100 for use in
connection with an
optoacoustic imaging device and/or a multimodal ultrasound and optoacoustic
imaging device.
The phantom 2100 comprises several targets 2102, 2104, 2106. In an embodiment,
the targets
2102, 2104, 2106 are dissimilar, one being particularly responsive to a first
stimuli but not a
second, one being particularly responsive to a second stimuli but not the
first, and one being
particularly responsive to both the first and second stimuli. In an
embodiment, the first stimuli
- 116 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
may be an optoacoustic pulse at a first wavelength and the second stimuli may
be an optoacoustic
pulse at a second wavelength. In an embodiment, the first stimuli may be a
traditional ultrasound
signal and the second stimuli may be an optoacoustic pulse at one or more
wavelengths. To
make materials responsive to the various stimuli, doping is generally used.
For optoacoustic
response, material is doped with an absorber at the relevant frequency or
frequencies. For
ultrasound response, material is doped to be denser. Using phantom 2100 the
response to the
first or second stimuli can be demonstrated and or calibrated in response to
the degree to which
2102, 2104, and/or 2106 targets are doped. This allows the determination of
the doping
percentages at which it is difficult to differentiate between target
responses.
[00356] Figure 23 shows a phantom 2300 for use in connection with an
optoacoustic
imaging device and/or a multimodal ultrasound and optoacoustic imaging device.
The phantom
2300 comprises several targets 2302, 2302 embedded in plastisol. In an
embodiment, the targets
2302, 2304 are generally linear and similar. In an embodiment, the targets
2302, 2304 are natural
or synthetic horsehair. Using phantom 2300 multiple modalities such as
optoacoustics and
ultrasound can be co-registered. In an embodiment, a multimodality probe is
coupled to the
phantom, and an image showing the output of each modality is presented on the
screen overlaid
upon one another. Using a joystick or other input device, an operator can
manually co-register
the images, thus providing co-registration for the multimodality probe. In an
embodiment, the
images of each of the modalities are compared by a computer, and automatically
co-registered.
[00357] Figure 22 shows an active phantom 2200 for use in connection with
an
optoacoustic imaging device and/or a multimodal ultrasound and optoacoustic
imaging device.
The phantom 2200 comprises an active target 2212 embedded in plastisol and
target control
2201. In an embodiment, active target 2212 comprises a linear array of
transducers 2210 on a
backing 2211; the transducers 2210 are operatively connected to target control
2201 through the
body of the active target 2212, connector 2214 and by electrical path 2208.
Target control 2201
can create signals that drive the transducers 2210. In an embodiment, target
control 801
selectively creates signals to output a known ultrasound pattern and/or
simulates an optoacoustic
return signal. Using phantom 2200 permits testing and calibration of the
optoacoustic return
signal receiving and processing portions of an optoacoustic device 100 without
concern for the
integrity of the light output system.
[00358] As discussed above and shown in the Figures discussed above, the
probe 102 may
have a linear array of transducers 1710 that are adapted to receive the
optoacoustic return signal
- 117 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
through an acoustic lens 1605. Other transducer geometries are also desirable.
Turning to
Figures 24A-C, in various embodiments, a linear transducer array may be
oriented with sides that
protrude at angles from the plane of the central portion of the array, or may
be in the general
shape of an ellipse or a semi-circle. Turning to Figures 25A-C, in various
embodiments, a
transducer array may be provided in a two dimensional shape as generally
illustrated. Although
the illustrations show only small numbers of transducers, e.g., 7 per line, in
practice, many more
transducers would be used. As discussed above, in an embodiment, 128 or more
transducers per
line, may be used. For example, in Figure 25A, an illustrative array is shown
comprising four
generally linear arrays of transducers aligned on simple Cartesian coordinates
in asterisk-type
configuration ands sharing a common center transducer. In Figure 25B, an
illustrative array is
shown comprising three generally linear arrays of transducers wherein the
transducers are
arranged similarly distant from one another on concentric rings in the various
arrays, and also
arranged in asterisk-type configuration and sharing a common center
transducer. In Figure 25C,
an illustrative array is shown comprising three generally linear arrays of
transducers arranged in a
simple grid.
[00359] With respect to each of numerous geometries shown, to develop an
image from
the optoacoustic return signal requires (i) that the transducers are coupled
to the volume 160
containing the target(s) of interest when used to detect an optoacoustic
return signal, and (ii) that
the detected optoacoustic return signal is processed using information
relating the relative
position of the transducers to each other in space. Transducers may be use in
a flexible array that
adapts to the shape of the volume 160 when coupled therewith, provided that
the relative position
of the transducers to each other in space is known, and used in processing the
optoacoustic return
signal.
[00360] In an embodiment, an optoacoustic probe can be used to detect the
optoacoustic
return signal by sampling the transducers for a period of time after the
optoacoustic inducement,
such as a laser, has been deployed. In an embodiment, at least some of the
desired content of the
optoacoustic return signal is in the frequency range of about 100 KHz to 12
MHz. Thus the
optoacoustic return signal may be sampled at 30 MHz, which is a sufficient
sampling rate for at
least some of the desired content of the signal. In an embodiment, the
sampling apparatus is
capable of sampling up to 256 channels at 65 MHz. In an embodiment, an
optoacoustic probe
may have 128 or 256 transducers, and may be sampled at or around 30 MHz.
- 118 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00361] In an embodiment, an optoacoustic probe can detect the
optoacoustic return signal
by sweeping through multiple transducer elements or through multiple groups of
transducer
elements. For example turning to Figure 25A, the 25 shown illustrated
transducer elements are
shown in four groups 2510, 2515, 2520, 2525 of seven, noting that each group
shares a common
center element. In an embodiment, after an optoacoustic pulse such as from a
laser, a first cycle
of the detection of the optoacoustic return signal can be conducted first
through one group 2510,
then a second group 2515, then a third group 2520, and then a fourth group
2525. Once that first
cycle of the detection of the optoacoustic return signal is complete, a second
cycle, a third cycle
and so on may continue. The sampling apparatus discussed in an embodiment
above capable of
sampling up to 256 channels 65 MHz is also capable of sampling two separate
arrays of 256
transducers at 30 MHz, or four arrays of 128 transducers at 30 MHz.
Accordingly, in an
embodiment as shown in Figures 25A-C, a sampling apparatus may be used to
sweep through
two or more groups of overlapping (e.g., Figures 25A-B) or unique (e.g.,
Figure 25C) transducers
and thus sample the optoacoustic return signal in response to a single
optoacoustic event, such as
the firing of a single laser pulse.
[00362] As will be apparent to one of skill in the art, sampling apparatus
are capable of
sampling at rates higher than the illustrative one discussed above. Using
sampling apparatus that
can sample more channels or at faster rates would permit a larger number of
total samples to be
generated in response to a single optoacoustic event. Accordingly, it is
within the scope of this
specification and the inventions disclosed herein, to use larger groups,
and/or more groups, of
transducers than are illustrated above, to be swept through in response to a
single optoacoustic
event.
[00363] Advantages exist in connection with each of the differing
transducer geometries
discussed above. The straight linear array is compact, cost efficient, easily
handled, and is the
most commonly used in standard ultrasound B-mode imaging. The curved or winged
linear
arrays may conform better to the irradiated volume, and thus, provide better
coupling. The non-
linear(multiple row, also known as 1.5 dimensional) arrays permit additional
angles from which
to resolve the optical return signal from a given voxel, which may improve
resolution and/or add
clarity and contrast to the image and/or may better support three-dimensional
imaging
applications. Flexible arrays may also provide better coupling with the
volume. The non-linear
arrays can allow transducer elements that are optimized for ultrasound to co-
exist with transducer
- 119 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
elements that are optimized for optoacoustics within the same probe. Different
transducer
elements are used to create either the US or OA images.
[00364] An optoacoustic return signal can be generally acquired within a
window of less
than about 100 microseconds. Using a generally accepted approximation for the
speed of sound
in tissue of around 1,500 m/s, a 100 microsecond acquisition window may
correspond to a depth
of up to about 15 centimeters. In an embodiment, an optoacoustic return signal
can be acquired
within a window of about 65 microseconds, and contain information from as deep
as about 10
centimeters. In an embodiment, the frequency of light events is anticipated to
be generally on the
order of every 50 to 100 milliseconds (0.05 to 0.1 seconds). Accordingly, the
data acquisition
may occur less than 1% of the time, and closer to between 0.1% or 0.2% of the
time, leaving
more than 99% of the time where no data acquisition is occurring. Electrical
noise may be
created by powering the light subsystem 129 and/or other components of the
system 100.
Accordingly, in an embodiment, to prevent electrical noise from affecting the
data acquisition, a
synchronization is utilized to prevent powering unnecessary components during
that period,
leaving power only to the preamps, analog-to-digital converters and
multiplexer. In an
embodiment, the synchronization between power and data acquisition allows for
the power
system to be optimally electrically quiet during the acquisition time period.
In an embodiment,
this may be achieved by powering down noisy digital components during this
period or allowing
charged capacitors to power the acquisition hardware at this time. In an
embodiment, this is
triggered by the same trigger that starts the acquisition cycle and is
controlled by the master
processor to control the turning on/off of the peripheral components not
involved with the
acquisition cycle. In an embodiment, this takes from a few nanoseconds to a
few microseconds.
In an embodiment, the same synchronization signal can be used to synchronize
one or more of
the other switching power supplies within and/or associated with the OA
system. By controlling
one or more such switching power supply, electrical noise produced by the
power supply (e.g.,
switching transients) can be caused to occur at the same time. In an
embodiment, by using a
synchronization signal, electrical noise produced by the power supplies in the
OA system can be
purposefully staggered, leaving temporal windows of electrical quiet during
which data may be
acquired.
[00365] In an embodiment, at least one switching power supply generating
power for the
light sources 130, 131 includes an external control for impeding operation of
its switching
operation ¨ hereinafter a blanking signal ¨ and the data acquisition is
adapted to sample during a
- 120 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
specific period after a pulse of light from a light source. For example, in an
embodiment,
sampling would begin 10 iLts after the light pulse, and sampling would
continue for approximately
65 iLts at a sampling rate of 31.25 Mhz. In an embodiment, the sync detectors
3903, 3913 could
be used to detect the light event. In another embodiment, sampling could begin
5 iLts after a light
pulse from the first light source, but 7 iLts after a light pulse from the
second light source, and
could continue for approximately 65 iLts at a sampling rate of 31.25 Mhz, for
the first light source,
or for approximately 63 iLts at a sampling rate of 31.25 Mhz, for the second
light source. Here
too, the sync detectors 3903, 3913 could be used to detect the light event and
distinguish the light
sources.
[00366] In an embodiment, the optoacoustic processing and overlay system
140 can
control the sequence of certain operations in the optoacoustic system,
including initiating the
light events from the light sources 130, 131, initiate the data sampling
operation sampling the
transducer data, and utilizing the blanking signal to impede the switching
operation of a
switching power supply during the period of data acquisition. In an
embodiment, prior to
initiating the acquisition of data, the optoacoustic processing and overlay
system 140 causes the
light event to occur, and initiates the blanking signal. Even at 20 frames per
second, the period
of data acquisition is just a small fraction of time, i.e., 20 x about 65 iLts
or comfortably less than
0.2% of the total operation time of the switching power, a safety margin can
be used, and the
blanking signal can be issued before data sampling begins, e.g., without any
delay after the sync
detection, and may be maintained for up to 100 iLts or more.
[00367] As discussed above, in an embodiment, the same transducers are
used to receive
acoustic-generated ultrasound and to receive the optoacoustic return signal.
The geometry of
acoustic-generated ultrasound transducers is not optimal for receiving the
optoacoustic return
signal. Accordingly, in an embodiment, separate transducers are used for the
acoustic-generated
ultrasound and the optoacoustic return signal. The acoustic-generated
ultrasound transducers can
have a narrower band because the transducer itself sends the signal that it
needs to detect. The
optoacoustic return signal transducer can have a wider band, such as, for
example, 50 KHz to 20
MHz. This wider band is preferred, among other reasons, because gain falls
faster with depth on
the optoacoustic return signal. Thus, in an embodiment, a plurality of
transducers is used to
receive the acoustic-generated ultrasound and a separate plurality of
transducers is used to
receive the optoacoustic return signal. In an embodiment the plurality of
transducers used to
receive the acoustic-generated ultrasound and the separate plurality of
transducers used to receive
- 121 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
the optoacoustic return signal comprise approximately the same number of
transducers. In an
embodiment the plurality of transducers used to receive the acoustic-generated
ultrasound and the
separate plurality of transducers used to receive the optoacoustic return
signal each comprise at
least 128 transducers, and more preferably, would comprise at least 192
transducers. In an
embodiment the plurality of transducers used to receive the acoustic-generated
ultrasound and the
separate plurality of transducers used to receive the optoacoustic return
signal each comprise at
least 256 transducers. In an embodiment, the transducers used to receive the
optoacoustic return
signal have a wider band frequency response than separate transducers used to
receive the
acoustic-generated ultrasound. In such an embodiment, the transducers used to
receive the
optoacoustic return signal have a frequency response from at least about 1 MHz
to 5 MHz, and
more preferably, from about 100 KHz to about 10 MHz, and even more preferably
from about 50
KHz to about 20 Mhz. In such an embodiment, the transducers used to receive
the optoacoustic
return signal may use high impedance amplifiers, such as 1 Kg2 or more, and
more preferably, 5
Kg2 or more. In such an embodiment, the transducers used to receive the
acoustic-generate
ultrasound would use amplifiers having an impedance of less than 1 Kg, and
more preferably
about 200 S. The use of separate transducers would eliminate the need for
relay system 110, and
the switching of the transducer outputs thereby between the optoacoustic
processing and overlay
system 140 and the ultrasound instrument 150.
[00368] As discussed above, in an embodiment, the same transducers are
used to receive
acoustic-generated ultrasound and to receive the optoacoustic return signal.
Where the same
transducers are used to receive acoustic-generated ultrasound and to receive
the optoacoustic
return signal, amplifiers should be used that have an impedance within the
range of about 1-10
Kg, and more preferably amplifiers should be used that have an impedance of
approximately 5
1(Q.
[00369] In an embodiment, the sampling of an optoacoustic return signal is
performed in a
variable manner, where the gain of the amplifiers associated with each of the
sampled channels is
adjusted over time, and is hereinafter referred to as time gain compensation
or TGC. TGC ramps
up gain on the acoustic input as the optoacoustic return signal becomes
fainter, thus more
accurately sampling the signal, and providing more normalized collected data
and maintaining
good signal-to-noise ratio as the signal become fainter. Optoacoustic return
signal becomes
fainter with time for several reasons, including that the later optoacoustic
return signals have
generally traveled further. Thus, generally optoacoustic return signal becomes
fainter as the
- 122 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
depth of a target increases. However, the magnitude (and thus needed gain) of
optoacoustic
return signals are also affected by the location and source of illumination.
Generally, less light
penetrates to deeper depths, and thus, the optoacoustic return signals are
fainter because an
optoacoustic event occurring at the surface of a volume generally induces a
smaller response at a
deeper depth. TGC is utilized to compensate for the later, fainter
optoacoustic return signals.
[00370] The optoacoustic device 100 may comprise sensors (not shown) that
can measure
power and from that infer both total and peak power of the light subsystem
129, and performance
and efficiency of the optical path 132. In an embodiment, sensors such as
photo detectors can be
placed within or in close proximity to the light subsystem 129 and within or
in close proximity to
the probe 102. In each case, the sensors would take a measurement during the
illumination of a
light 130, 131 which can be used to infer total and peak power. For this
purpose, one or more
sensors can be placed inside the probe 102 to measure reflection from the
optical window.
Similarly, one or more sensors can be placed within the light subsystem 129 to
measure light
reflected therein. Deviation over time in the measurements inferred between
the two sensor
locations may be indicative of anomalies in the light path 132.
[00371] Discussing now an embodiment of the system having sensors (not
shown) such as
photo detectors within or in close proximity to the probe 102. In an
embodiment, one or more
sensors may be placed within the probe, in the gap 1802 to measure reflection
from the optical
window. Alternatively, or additionally, in an embodiment, one or more sensors
may be provided
light directly from a component of the light path 132, such as from one or a
small plurality of the
optical fibers that make up the light path 132. Alternatively, or
additionally, in an embodiment,
one or more sensors may be provided light by another path provided within the
probe. Thus, for
example, one or more sensors could be located within the end of the probe
opposite the optical
windows 1603, and an auxiliary light path (not shown) can e.g., carry light
directly from the light
path 132 or reflected from the optical window or otherwise, to the one or more
sensors.
Alternatively, or additionally, in an embodiment, one or more sensors may be
arranged to detect
light originating in the light path 132 after it has been reflected from the
surface of three-
dimensional volume 160. Using information from sensors arranged to detect
light reflected from
the surface of three-dimensional volume 160, in combination with information
concerning the
light transmitted through the optical window 1603 towards the volume 160 (such
as information
from sensors measuring output from the light subsystem 129 or from the optical
window 1603),
- 123 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
can provide diagnostic information concerning the volume 160. Such diagnostic
information
may include the absorptiveness, or the darkness, of the volume 160.
[00372] In an embodiment, the foregoing sensors can be tuned to specific
wavelengths
through the use of an optical filter. Thus, for example, sensors within or in
close proximity to the
probe 102, sensors within or in close proximity to the light subsystem 129,
sensors receiving
light from an auxiliary light path and/or sensors arranged to detect light
reflected from the
surface of the volume 160, can be filtered to discriminate between the
wavelengths of light
produced by the light subsystem 129 and/or any extraneous light. Accordingly,
sensors may be
provided to detect (or potentially to reject) specific light frequencies, such
as the light from one
of the two light sources 130, 131.
[00373] In an embodiment, one or more sensors within or in close proximity
to the probe
102 can be used as part of a triggering system and method for starting
detection optoacoustic
return signal data. In such a triggering system or method the detection of a
specific threshold
value of light by the one or more sensors can send a detection control signal
to the computing
subsystem 128. In an embodiment, the detection control signal is sent over the
power and control
signal lines 109 to the optoacoustic processing and overlay system 140. The
detection control
signal is used by the computing subsystem 128 to initiate (after any
appropriate delay, if any) the
process of obtaining the optoacoustic return signal data, for example, by
"sampling" data from
the ultrasound transducer elements. As discussed above, because the one or
more sensors can be
optically filtered to detect specific light frequencies, the detection control
signal may be specific
to one or more frequencies of light, and may initiate differing sampling
rates, or delays, based
upon the different frequency of light.
[00374] In an embodiment, one or more sensors within or in close proximity
to the probe
102 can be used as part of a system and method for safely starting the
optoacoustic system 100
and then bringing the laser to its safe power potential. Although laser light
sources (e.g., 130,
131) generally have a controllable power output, many factors can affect the
total power output
by a light source regardless of its setting. Ambient temperature, for example,
may affect the
power output by a laser. Similarly, fluctuations in electrical power can also
affect the power
output by a laser. In addition, the light path 132 can negatively affect the
light output of laser
light sources (e.g., 130, 131). Fibers within the light path 132 can burn out,
or lose transmissive
properties as they age or are used. Moreover, fibers that are positioned in a
bend can lose
transmissive properties. Thus, the setting of a light source (e.g., 130, 131)
to a particular output
- 124 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
level is not necessarily determinative of the light that reaches the other end
of the light path 132,
and ultimately, the volume 160. Accordingly, in an embodiment, the light
source (e.g., 130, 131)
is set to a relatively low power. The relatively low power should be selected
to be a power that,
in the event everything is functioning at its peak output or transmissiveness,
would not exceed a
desired maximum fluence on the volume 160. Once the light source (e.g., 130,
131) is pulsed, a
measurement from the one or more sensors is used to infer the fluence of light
delivered to the
volume 160. In the event that this inferred fluence is lower than the desired
fluence level (or a
desired range of fluence levels), the output from the light source can be
increased, and the
process repeated. Likewise, in the event that the inferred light fluence is
higher than a desired
maximum, the output from the light source can be decreased. Because the system
100 is capable
of a significant number of laser events per second, the rate of increase to
the light output, and
thus, the potential increase in the fluence level between laser events, can be
kept relatively small.
In an embodiment, the amount of change in output from the light source may be
larger when the
inferred fluence is farther away from the desired fluence level (or a desired
range of fluence
levels), and smaller when the inferred fluence is closer to the desired
fluence level.
[00375] In addition to providing a method for safely starting the
optoacoustic system and
bringing the laser to its safe power potential, the same process can be run as
a closed loop control
to ensure that the laser fluence is being monitored and controlled, and that
to the extent it exceeds
a predefined threshold such coming within some margin of a safety limit, its
output power can be
lowered. Similarly, operating the process as a closed loop control can also
ensure that the laser
output is being set to a maximum desirable setting even as the operating
conditions of the system
100 (e.g., ambient temperature and electrical power) change, and regardless of
the existing or
changing condition of the light path 132. Keeping the laser at or close to its
highest safe level
permits the largest light fluence, and thus, strongest optical return signal.
In an embodiment, one
or more of the following: the target fluence level, the acceptable hysteresis
around the target
fluence level and a maximum fluence level, are user selectable, and when
selected can be used by
the processing running as a closed loop control to maintained the laser as
specified. The closed
loop control process can be used to normalize pulse-to-pulse power output.
[00376] In an embodiment, where the measurement taken at the one or more
probe-
proximate sensors falls below a predetermined threshold for a given laser
output, as a failsafe, the
lasers may be shut down. Such a level may reflect a failure or detachment of
the light path 132,
or other unsafe condition.
- 125 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00377] In an embodiment having one or more sensors within or in close
proximity to the
probe 102 and one or more sensors within or in close proximity to the light
subsystem 129, the
sensors can be utilized as part of a system for and method to detect faults in
the light path 132 or
to provide a safety control for faults in the light path. In an embodiment,
the light output of the
light subsystem 129 would be expected to be proportional to the light output
of the light path 132
and the light fluence exiting the optical windows 1603. The use of one or more
light subsystem-
proximate sensors can permit detection of differences in the expected amount
of the light incident
on the several sensors. As discussed above, the light path 132 can negatively
affect the light
output by of laser light sources (e.g., 130, 131). For example, the light path
132 can be
negatively affected by burn out, old or broken fibers within the bundle. Thus,
setting a light
source (e.g., 130, 131) to a particular output level is not necessarily
determinative of the light that
reaches the other end of the light path 132, and ultimately, the volume 160.
By employing both
one or more light subsystem-proximate sensors and one or more probe-proximate
sensors,
performance of the light path 132 can be detected and monitored.
[00378] In an embodiment, the one or more light subsystem-proximate
sensors are used to
measure the power of the light entering the light path 132 and one or more
probe-proximate
sensors are used to measure the power of the light that has been transmitted
through the light path
132. The measurement taken at the one or more light subsystem-proximate
sensors may be used
to predict a measurement at the one or more probe-proximate sensors. In an
embodiment,
deviation from the predicted measurement at the one or more probe-proximate
sensors can be
used to identify potential problems with the light path 132. In an embodiment,
the sensor
readings are recorded with other data concerning the event. In an embodiment,
deviations are
assessed to determine whether action needs to be taken, for example, whether
the user needs to
check the light path 132 connections, or whether the light path 132 is in need
of maintenance
(e.g., straightening, cleaning, lapping and polishing or other maintenance) or
even replacement.
In an embodiment, where the measurement taken at the one or more probe-
proximate sensors
deviates from its predicted measurement by more than a predetermined amount,
as a failsafe, the
lasers may be shut down. Such a deviation may represent a failure or
detachment of the light
path 132 or other fault or unsafe condition.
[00379] In an embodiment having one or more sensors within or in close
proximity to the
probe 102 and/or one or more sensors within or in close proximity to the light
subsystem 129, the
measurements from the sensors, along with the other settings of the machine
(including the
- 126 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
commanded light output) should be stored with the data other data associated
with the light pulse,
such as the optoacoustic return signal.
[00380] In an embodiment, a calibration phantom comprising one or more
embedded
photosensitive sensors is provided. As with the above-described sensors, the
sensors in the
phantom can be used to infer total and peak power, as well as light
distribution. Deviation over
time in the measurements inferred between the phantom sensors and the other
sensors may
similarly be indicative of anomalies. Moreover, changes over time between the
readings of the
various sensors within the phantom or within the probe may be indicative of
issues with the
evenness of light output of the probe. The use of such sensors rather than the
system transducers
avoids acoustic involvement, thus eliminating error introduced by the
transducers themselves.
[00381] In an embodiment, a second calibration phantom may be provided
with acoustic
targets rather than sensors. The use of such a phantom eliminates any error
that may be
introduced by the sensors themselves. Calibration using both the acoustic
target and sensor
phantoms would provide a cross-check and mitigate the potential for
calibration error. Time gain
compensation must be properly calibrated.
[00382] Turning briefly to Figure 40, an embodiment of a calibration
system receiving unit
4000 is shown. The calibration system receiving unit 4000 comprises an opening
4006 sufficient
in height and width to receive a probe 102, sensors 4005 for sensing the
presence of the probe
102 when it is inserted in the calibration system receiving unit, stops 4008
for preventing over
insertion of the probe 102, and arresting its insertion at a fixed distance
from a meter 4007. In an
embodiment, meter 4007 is a sensor calibrated at each of the predominant
wavelengths put out by
the light subsystem 129. In an embodiment, meter 4007 is a sensor that can
measure light energy
and is calibrated for an ND:YAG laser and an Alexandrite laser. In an
embodiment, the meter
4007 is a photo detector. In an embodiment, the meter 4007 is a thermal
measurement device. In
an embodiment, meter 4007 is large enough to measure the entire light output
of the probe 102.
In an embodiment (shown), the power meter is not large enough to measure the
entire light
output of the probe 102, but the total output is inferred based on the overlap
of the area of the
meter 4007 and the area of the optical window(s) 106. When the light subsystem
outputs a pulse
of light that the pulse emits from the distal (active) end of the probe, the
sensor provides a
measurement proportional to the light energy and/or power. In an embodiment,
the voltage to the
light subsystem and the Q-switch delay are constant, and thus, to adjust power
output optical
attenuator 3902, 3912 are employed.
- 127 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00383] In an embodiment, a calibration mode of the optoacoustic
processing and overlay
system 140 operates at least one of the light sources 130, 131 of the light
subsystem 129 only if
the probe sensors 4005 detect the presence of the probe 120 in the calibration
system receiving
unit 4000. After causing at least one of the light sources 130, 131 to cause a
light event, the
optoacoustic processing and overlay system 140 determines the power or energy
measured by the
meter 4007 and determines whether adjustment is appropriate. Where the power
or energy
measured at the probe 102 by the meter 4007 is either too high, or too low,
adjustment may be
made by adjusting (e.g., rotating) the optical attenuator 3902, 3912
associated with the light
source 130, 131 requiring more or less output energy or power at the probe
102. In an
embodiment, the output of sync detector 3903, 3904 may be used in calibration
to determine
which of the light sources 130, 131 caused a condition that requires
adjustment, and permitting
calibration function to then adjust the correct optical attenuator 3902, 3912.
[00384] In an embodiment the meter 4007 is calibrated to determine power
at the first and
second predominant wavelength and adapted to measure power at the first
predominant
wavelength in proximity to at least one optical window 106 after a sync signal
reflecting a light
event at the first light source is detected, and to measure power at the
second predominant
wavelength in proximity to at least one optical window 106 after a sync signal
reflecting a light
event at the second light source is detected; and the apparatus optoacoustic
system to electrically
attenuates appropriate optical attenuator, if necessary, based on the power
measured by the power
meter.
[00385] In an embodiment, a meter could be located proximal to the optical
windows 106
or otherwise able to measure light output from the light path 132. In such an
embodiment, the
optoacoustic processing and overlay system 140 could obtain a measurement from
the meter after
each operation of a light source (or at such other convenient interval as is
desired) and provide
increased or decreased optical attenuation as appropriate based on such
measurements. A meter
operating in proximity to the optical window 106 may use internal reflection
from the optical
window to infer the total energy or power. A meter operating in a manner to
measure light
output from the light path 132 may use a dedicated fiber or plurality of
fibers from the light path
to infer the total energy or power. In an embodiment, the readings of a meter
operating in a
manner to measure or infer light output from the light path 132 can be
compared to or monitored
against the readings of a power meter 3904, 3914, as changes in the relative
strength of these two
measurements may be indicative of a maintenance or safety issue.
- 128 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00386] In an embodiment, calibration history is recorded for maintenance
purposes. For
example, using the calibration history can assist in knowing when or if an
optical attenuator is
nearing the end of its useful life, and thus requires replacement. Similarly,
identifying sudden
changes may indicate a system fault, e.g., burnt fibers in the light path or
loss of alignment at the
light output port.)
[00387] Turning now to Figure 41 which shows a schematic diagram
illustrating an
embodiment of a hardware testing system for use in testing certain portions of
the optoacoustic
system. In an embodiment, the hardware testing system comprises a light pulse
sensor 4107
adapted to sense a light pulse output from the light output port of the
chassis of an optoacoustic
system, e.g., cart 3200, and in response thereto to transmit signals over a
plurality of conductors
operatively connected to the optoacoustic processing and overlay system 140.
In an
embodiment, the plurality of conductors that are used by the hardware testing
system are
assembled into a bundle and terminated at a multi-pin connector having the
same form factor as
the multi-pin electrical connector for connecting the electrical path 108 and
control line(s) 109
from the probe 102 to the system chassis. The hardware testing system also
comprises a signal
output unit 4100. In an embodiment, the signal output unit 4100 stores a
plurality of signal sets
and may output one of them in response to a triggering event. In an
embodiment, the light pulse
sensor 4107 can distinguish between light events occurring at different
wavelengths, e.g.,
between a pulse from an ND:YAG laser and a pulse from an Alexandrite laser,
and can send a
corresponding trigger over one or more trigger wires 4106. In an embodiment,
the light pulse
sensor 4107 comprises two separate light sensors, one that sends a trigger
over its trigger wire
4106 for the ND:YAG laser pulse, but not for the Alexandrite laser pulse, and
the other that
sends a trigger over its trigger wire 4106 for the Alexandrite laser pulse,
but not for the ND:YAG
laser pulse. In an embodiment, a single trigger wire carries the two separate
distinguishable
triggers. In an embodiment, the light pulse sensor may reside within signal
output unit 4100, and
a waveguide connected to the light output port may direct the light pulse to
the light pulse sensor.
[00388] In an embodiment, at least some of the signal sets stored by the
signal output unit
4100 may correspond to data that if received in the normal optoacoustic mode
as a result of the
triggering light source, would be resolved to a known optoacoustic image
(e.g., an optoacoustic
image of a specific mass in tissue). In an embodiment, the signal sets are in
pairs, having one
signal set respond to one light source and the other of the pair respond to
the other light source,
thereby providing information that, after one pulse of each light source would
resolve to a known
- 129 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optoacoustic image and its associated parametric data ¨ in other words, being
essentially
indistinguishable as viewed through the system from an actual live
optoacoustic image, except
that no probe 102 is used. The signal set should be transmitted in a manner
that will not result in
sampling error by the optoacoustic systems' ADC. In an embodiment, e.g., a
digitally stored
signal set should be transmitted at a rate that is at least twice the ADC
sampling rate if it is
asynchronous with the sampling. In an embodiment, signal set pairs can be
created from
sinograms comprising data actually received by the optoacoustic system in
response to its
operation on the tissue of a subject. In an embodiment, signal set pairs can
be created by up-
sampling sinograms comprising data actually received by the optoacoustic
system in response to
its operation on the tissue of a subject. The use of the optoacoustic device
with these signal sets
permits an external verification on the system's processing of known data,
without variations that
may be due to different tissue or other functional variations. Moreover, the
use of the
optoacoustic device with these signal sets controls for ¨ by elimination ¨
problems that may exist
in the probe 102, light path 132 or electrical path 108.
[00389] In an embodiment, at least some of the signal sets stored by the
signal output unit
4100 may correspond to data that could not reasonably result from operation of
the optoacoustic
system ¨ hereinafter diagnostic signal sets. Examples of a diagnostic signal
set may include a
specific sine wave occurring on any one or group of the channels could not
reasonably result
from operation of the optoacoustic system. A near infinite number of other
diagnostic signal sets
can be created. In an embodiment, the optoacoustic processing and overlay
system 140 can
recognize one or more of these diagnostic signal sets, and in response
thereto, perform one or
more system diagnostics associated with the specific diagnostic signal set
received.
[00390] In an embodiment, the signal output unit 4100 comprises a selector
4108. The
selector 4108 can be used to select between signal sets, or between signal set
pairs. The selector
4108 may be a mechanical switch, or implemented in software with an
appropriate user interface,
e.g., touchscreen. In an embodiment, a signal output unit has a variety of
signal set pairs, at least
some of the signal set pairs cause the optoacoustic system to display known
images and
parametric data in response to the operation of both light sources, and at
least some of the signal
set pairs cause the optoacoustic system to perform specific diagnostics in
response to the
operation of one or both of the light sources.
[00391] In an embodiment, the hardware testing system may also be adapted
to receive
and respond to ultrasound energy. In an embodiment, at least one ultrasound
signal set reflecting
- 130 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
a known ultrasound image is returned to the optoacoustic system in response to
receiving
ultrasound energy from the optoacoustic system via the multi-pin connector and
electrical path
4105. In an embodiment, the an ultrasound signal set may correspond to one or
more of the
signal set pairs that are used to respond to optical pulses, and in this
manner, the optoacoustic
system can present overlaid images computed from the signals returned from the
hardware
testing system. In essence, the optoacoustic system need not recognize that
the returned signals
are coming from a testing system rather than from actual optoacoustic
operation. Likewise, the
selector 4108 on the signal output unit 4100 can be used to select between
groups that include
both a signal set pair which are sent in response to optical energy and an
ultrasound signal set
that is sent in response to ultrasound energy.
[00392] In an embodiment, at least some of the signal sets stored by the
signal output unit
4100 may correspond to data that if received in the normal optoacoustic mode
as a result of the
triggering ultrasound energy, could be resolved to a known ultrasound image
(e.g., by
beamforming). The signal set should be transmitted in a manner that will not
result in sampling
error by the optoacoustic systems' ADC. In an embodiment, e.g., a digitally
stored signal set
should be transmitted at a rate that is at least twice the ADC sampling rate
if it is asynchronous
with the sampling. The use of the optoacoustic device with ultrasound signal
sets permits an
external verification on the system's processing of known data, without
variations that may be
due to different tissue or other functional variations. Moreover, the use of
the optoacoustic
device with these signal sets controls for ¨ by elimination ¨ problems that
may exist in the
ultrasound transducers or electrical path 108. In an embodiment, at least some
of the diagnostic
signal sets may be sent in response to ultrasound energy.
[00393] In yet a further embodiment, linear or non-linear arrays may be
physically
separated from each other, but the data there-from may be recovered in
response to the same
optoacoustic event. Turning to Figure 26, as an illustrative example, a two-
armed (or more)
forceps-like probe 2600 may contain linear or non-linear transducer arrays
2620 extending from
arms 2615 that can be physically positioned using finger grips 2605, 2610 at
the time of use, for
example, on each side of a volume to be irradiated. In another example (not
shown), two or more
of the fingers of a glove could contain linear or non-linear arrays of
transducers which can be
manually positioned. In each case, although preferable, it is not necessary to
know the
orientation of one array with respect to the other in use. And while it is
necessary that the
optoacoustic event irradiate the volume sufficiently to permit the at least a
portion of the
- 131 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
transducer arrays coupled to the volume to detect an optoacoustic return
signal, it is not necessary
that the optoacoustic event is generated from the probe.
[00394] Turning to Figure 27, a forceps-like probe 2700 for use in
generating an
optoacoustic image by acquiring data in a forward transmission mode is shown.
The probe 2700
may contain a linear or non-linear transducer array 2720 situated across from
an optical window
2730 that can project light output from a suitable light source such as a
laser. The separation of
the optical window from the transducer array mitigates numerous sources of
noise that interfere
with the sampling process of the optoacoustic return signal.
[00395] Each transducer in probe 102 may exhibit slight variations in
operation.
Accordingly, in an embodiment, once completed, probe 102 is tested in
connection with one or
more known test subjects such phantoms (see Figures 7-9) and the probe's
measured response
from the test subject is recorded. In an embodiment, the test subjects will
produce a known
optoacoustic return signal, either in response to a known optoacoustic event,
or, by active control
of the phantom. Variation from the known/expected optoacoustic return signal
can be identified,
and associated with each specific channel (e.g., transducer) comprising the
variation. In this
manner, the probe's own response characteristics ¨ to the extent they may
differ from probe to
probe ¨ can be accounted for, and may be normalized in later processing. Thus,
if a particular
transducer produces a signal that differs from the expected signal, that
difference can be
accounted for, and then later normalized.
[00396] In an embodiment, information associated with a probe's own
response
characteristics may be stored within the probe itself, and can be reported to
the optoacoustic
processing and overlay system 140 via power and control signal lines 109. In
an alternative
embodiment, information associated with a probe's own response characteristics
may be stored
outside the probe, and can be associated with a serial number or other
identifier of the probe.
The optoacoustic processing and overlay system 140 can obtain the probe
response
characteristics after identifying the probe for use. In an embodiment, the
probe response
characteristics may be stored in an network accessible location, either on a
local disk, network, or
on the Internet, and are made accessible to the optoacoustic processing and
overlay system 140
via a connection (not shown) to that disk, network or the Internet. In an
embodiment, the
optoacoustic processing and overlay system 140 would obtain a unique
identifier from the probe,
and would thereafter query a database on the local device, network, or over
the Internet, to obtain
response characteristics for the probe associated with the unique identifier.
Probe response
- 132 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
characteristics may be recorded and stored at or near the time the probe is
manufactured. In an
embodiment, probe response characteristics may be updated by running a
specialized test on the
probe ¨ the test having a known/expected response.
[00397] The probe identifier may be obtained by the optoacoustic
processing and overlay
system 140 after machine startup, but before engaging the light output. In an
embodiment, the
probe identifier is recorded on a bar code on the probe, and the bar code is
scanned prior to the
device causing light output. In an embodiment, the probe identifier is
recorded on a computer-
readable memory in the probe, and is queried by, or reported to the
optoacoustic processing and
overlay system 140 after startup, but prior to engaging the light output.
[00398] Because the probe identifier is known, the device can maintain
statistics of probe
usage. For example, in an embodiment, the device may maintain statistics of
the operation of the
probe in optoacoustic mode, including, e.g., the number and type of light
output events that have
occurred, and the number of ultrasound events that have occurred. Statistics
can also be
maintained concerning total light energy output from the probe (which may be
deduced from an
internal optical sensor, not shown). In an embodiment, the response
characteristics of the probe
and the probe statistics can be available to any device 100 on which the probe
102 is mounted.
Thus, for example, such characteristics and statistics can be stored in a
manner that they are
accessible over the Internet. In an embodiment, a VPN is used for security on
the Internet.
[00399] In an embodiment where the light path 132 is fixedly attached to
the probe 102,
the probe usage statistics may also be relevant to the fiber optics. For
example, the fibers in the
light path 132 may degrade with time and/or use resulting in some loss of
transmission, e.g.,
broken or burned fibers. Accordingly, in an embodiment, the device can
maintain statistics
relevant to total light energy, peak light energy and the number of pulses
passed through a light
path 132. In an embodiment, sensors in the probe can detect information about
the energy output
of the light path, and sensors in the light subsystem 129 can detect
information about the energy
output of the light subsystem 129. By detecting variation in the sensors at
the two ends over
time, maintenance issues can be identified. For example, seeing a decrease at
the probe-side
sensors relative to the light subsystem-side sensors may indicate that the
light path 132 is
degrading and needs replacement. Moreover, a specific difference between the
probe-side
sensors and the light subsystem-side sensors may result in a condition that
causes the device 100
to indicate that it is in need of maintenance. In an embodiment, where the
difference is greater
- 133 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
than a specific safety threshold, the device 100 may fail to continue to emit
light events. In an
embodiment, the information reported by these sensors may be stored with the
usage statistics.
[00400] In an embodiment where the light path 132 is completely or
partially detachable
from the probe 102, the detachable portion of the light path may have its own
unique identifier.
Where the detachable portion of the light path has its own unique identifier,
usage statistics that
relate to that portion of the light path may be maintained in much the same
manner as the usage
statistics for the probe, but associated with the light path or portion.
[00401] In an embodiment, serialized components, that is, components such
as a probe 102
or a light path 132 may comprise a memory for storing data concerning
utilization of the
serialized component. Log files can be written to such memory. In an
embodiment the memory
is affixed to the component and accessible to the optoacoustic processing and
overlay system 140
via power and control signal lines 109. In an embodiment the memory is affixed
to the
component and accessible other software for reading and writing logs, which
may execute on the
optoacoustic processing and overlay system 140, via another electrical (e.g.,
conductive wires),
optical (e.g., using a fiber optic waveguide or infrared transmission), radio
frequency (e.g.
Bluetooth or other radio frequency transmission), as would be apparent to one
of skill in the art.
[00402] Turning briefly to Figures 32 and 33, an embodiment of an
optoacoustic system is
implemented in the form of a cart 3200 having wheels 3282 for portability. The
optoacoustic
system comprises displays 3212, 3214 for some types of output to an operator,
and user input
devices 3216 including a keyboard and trackball as well as dials, buttons and
switches provided
for receiving input from an operator. Integrated electrical path and power and
control signal lines
108/109 is connected to a probe 102 (largely obscured by a safety cover) on
one end, and to the
cart 3200 via a multi-pin connector 3208. Likewise, a sheathed light path 3232
is connected to
probe 102 on one end, and to the cart 3200 via a fiber optic connector 3250. A
foot switch 3300
is connected to the cart 3200 by a hardwired connection 3260, and provides for
a hands-free
means of engaging and disengaging the operation of the optoacoustic system.
[00403] In an embodiment, the probe component, consisting of the probe
102, the
integrated electrical path 108/109 and its multi-pin connector 3208, the
sheathed light path 3232
and its side of the fiber optic connector 3250, further comprises a memory
(not shown). In an
embodiment, the memory could be located within the probe 102 housing, within
the multi-pin
connector 3208 housing. In another embodiment, the memory could be located
anywhere within
or upon the probe component, or even external to the probe component. The
memory is capable
- 134 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
of storing data concerning utilization of the probe component. In an
embodiment, a unique
identifier is associated with the probe component, and may be stored in the
memory, or in
another memory associated with the probe component. In an embodiment, the
unique identifier
may be printed on the probe component, or placed on the probe component in the
form of a bar
code or other optically recognizable computer code. In an embodiment, the
unique identifier
may be stored in an RFID tag embedded in or associated with the probe
component.
[00404] As the optoacoustic device operates, e.g., to create optoacoustic
images, software
which may operate in the optoacoustic processing and overlay system 140 or on
another
processor can accumulate information concerning the use and response of the
probe component.
Then, on command or at specific intervals, such information, or parts or
summaries of that
information may be written to the probe component memory as a log entry. In an
embodiment,
the specific intervals may comprise one or more of the following: each light
event (i.e., pulse of
light) traversing the light path 109; each time a pre-specified number of
light events have
traversed the light path; each interval during which the foot switch 3300 is
used to operate the
optoacoustic system; each patient session, which may be designated by the
operator using the
user input devices 3216; each power cycle of the optoacoustic system (i.e.,
from the time it is
turned on until the time it is turned off); or upon elapsing of a time
interval, such as, e.g., a
second, a minute, or ten minutes.
[00405] In an embodiment, a log entry includes one or more of the
following: time/date;
unique identifier associated with the probe component; version information for
any hardware or
software comprising the optoacoustic system; counters, measurements or
statistics relevant to
total light energy, peak light energy and the number of pulses passed through
a light path 132
during the interval, since a previously specified time (such as the last
maintenance of the probe
component) or since the probe component was placed into service; counters,
measurements or
statistics relevant to performance or characteristics of the light path or
transmission loss from the
cart's light output to the probe's light output; counters, measurements or
statistics relevant to the
performance or characteristics of the probe's ultrasound transducer array or
its elements; or
counters, measurements or statistics relevant to the performance or
characteristics of any of the
probe's other discrete components.
[00406] In an embodiment, previously written logs may be read and/or
analyzed before
normal operation of the optoacoustic system. The information read from
previously written logs
may be used to form a baseline for ensuring safe and efficient operation of
the system, and to
- 135 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
determine maintenance needs. In an embodiment, previously written logs may be
read and
analyzed as part of a maintenance function for the optoacoustic system.
Significant changes in
measurements or statistics relevant to performance or characteristics may
indicate a need for
maintenance. In an embodiment, significant changes in measurements or
statistics relevant to
performance or characteristics of the probe component or its constituent parts
are reported to the
system operator, or to maintenance personnel.
[00407] In an embodiment where a probe 102 is separable from a light path
132, electrical
path 109 and/or power and control lines 108, any of these constituent parts
may be separately
serialized, and a separate memory may be maintained for the part itself, apart
from the assembled
probe component. For example, in an embodiment, a separable light path 132
comprises a
unique identifier and memory separate from that of a probe component including
an integrated
electrical path 108/109 and its multi-pin connector 3208. In another example,
in an embodiment,
a separable light path 132, and electrical path 109 with its multi-pin
connector 3208 each have a
unique identifier and memory, separate from that of a probe component
including power and
control lines 108. In a similar manner, other components for which usage
statistics or operational
information is required may be separately serialized, and given their own
unique identifier and
memory.
[00408] One use of the device 100 is performing imaging examinations on
humans for
breast cancer detection. A clinical device 100 may be a multimodality system
incorporating
optoacoustic imaging capability and ultrasound imaging capability. An
advantage of optoacoustic
imaging over ultrasound imaging alone is that it provides very high contrast
images which may
provide for the direct functional evaluation of tumors.
[00409] A block diagram of an embodiment of the clinical system is shown
in Figure 28
that illustrates the interaction between major subsystems and the type of
signals they represent.
In an embodiment, device 100 provides an integrated system consisting of the
following
subsystems: ultrasound subsystem 2802, optoacoustic electronics subsystem
2804, power supply
subsystem 2806, probe 102 and illumination/laser subsystem 2808, which may be
housed in one
console, and the control and display subsystem 2810 that can be attached to a
console. The
ultrasound subsystem 2802, the optoacoustic electronics subsystem 2804 and the
control &
display subsystem 2810 will be referred to hereinafter collectively as the
UOA.
[00410] The ultrasound subsystem 2802 may be, e.g., a fully functional
stand-alone
ultrasound system. The ultrasound subsystem 2802 includes an ultrasound
transmitter 2812 that
- 136 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
outputs an ultrasound signal that is used to stimulate tissue. The ultrasound
transmitter 2812
provides its output to a relay board 2814 in the optoacoustic electronics
subsystem 2804 which
switches the ultrasound signal to the probe 102. The ultrasound subsystem
further includes a
data acquisition board, or DAQ, that receives ultrasound signals from the
relay board 2814 and
processes them for transmission to and further processing by a computer 2816.
The computer
2816 provides signal processing, user interface, and command and control
functionality through
software. The computer 2816 includes one or more computer-readable medium for
storage of
programming as well as data generated by the system. The computer-readable
medium may be
in the form of volatile and/or non-volatile RAM, ROM, solid state drive,
optical media, magnetic
media (e.g., hard drive) or other storage device. The memory and storage may
be integrated into
or physically separate from the remaining components of the computer. The
computer 2816
further receives and transmits command and control signals to the DAQ for
control of the data
acquisition process and the ultrasound transmitter.
[00411] The optoacoustic electronics subsystem 284 includes a relay board
2814 that
provides switching functionality for alternately switching received ultrasound
signals to the DAQ
of the ultrasound subsystem 2802 and received optoacoustic signals to a
digital acquisition and
processing (DAP) board 2818. The relay board 2814 includes firmware for both
switching
control and timing control. In an embodiment, flex circuits that form
ultrasound transducers for
both transmitting and receiving ultrasound signals are integrated into the
relay board 2814. The
DAP 2818 receives and processes the OA signal and outputs processed OA signals
to the
computer 2816. The computer 2816 provides command and control signals via a
backplane to
the DAP 2818 and the relay board 2814, and provides timing signals via the
backplane to the
illumination/laser subsystem 2808.
[00412] Figure 29 shows a block diagram illustrating the illumination
subsystem 2808 and
control interfaces of the system 100 in accordance with an embodiment thereof.
Triggers are
TTL positive for activation. Some of illumination subsystem external control
and interfaces
include interlocks, photo diode based outputs (6), grounds, R5232, power and
optical port.
[00413] Figure 30 shows a pulse diagram illustrating a radiation
restriction in the system
100.
[00414] In an embodiment the device 100 uses a hand held probe 102
including an array of
transducers and an opening through which laser light can pass. In use, an
operator manipulates
controls and views the display as they move the probe 102 over the body or
other volume to
- 137 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
identify critical image characteristics. In an ultrasound mode the laser light
source has no
emission. In an optoacoustic mode the laser emits light according to specific
preconfigured
and/or operator set up parameters. In an embodiment the hand held probe may be
manipulated in
a similar fashion to the manipulation of an ultrasound probe. In an
embodiment, the device 100
includes an operator selectable operational mode whereby an optoacoustic mode
and ultrasound
mode are interlaced.
[00415] In an embodiment the clinical device 100 includes an illumination
source 1408
capable of providing two output wavelengths according to specific
preconfigured and/or operator
set up parameters. In an embodiment, the operator will be able to select
either an Nd:YAG laser
output at 1064nm or an Alexandrite laser output at 757nm, or to select the use
of both laser
outputs. When two wavelengths are selected, the laser subsystem, according to
specific
preconfigured and/or operator set up parameters, may alternate between the two
wavelengths one
after the other, or in other preconfigured or operator set up cycles. In an
embodiment, laser
operating parameters such as energy, pulse rate, and wavelength will be
operator selectable, and
subject, however, to specific preconfigured parameters.
[00416] In an embodiment, communication of the laser energy will be via a
fiber optic
bundle with a detachable mechanism. The detachable mechanism for interfacing
the laser output
to the fiber optic bundle includes a safety interlock/laser shutdown if
disconnected. In an
embodiment, the laser subsystem components include heat exchangers; pulse
drivers; direct laser
controls; laser power supplies; laser power management; laser head(s),
cavities and optics;
control and drive electronics; electronic interface ports; and a laser output
port.
[00417] In an embodiment, the laser is completely controlled by the UOA
control system.
The clinical device may be powered ON/OFF by the use of a low current key
switch located near
the user control panel. Through the action of this low current switch, closure
will cause the
secondary output of an isolation transformer's 230 VAC to be applied to each
of the subsystems,
including the laser. Opening this switch removes power from each of the
subsystems.
[00418] In an embodiment, the laser subsystem consists of a Q-Switched
Nd:YAG laser
and an Alexandrite Q-Switched laser with a common concentric output connector
designed to
have a fiber optic bundle attached. It contains all necessary electronics,
cooling, power
management, optics, and connections necessary to meet operational
requirements.
[00419] As discussed above, according to specific preconfigured
parameters, in an
embodiment the operator will be able to select the clinical device 100 laser
light output from the
- 138 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
Nd:YAG (1064 nm) only or select laser light output from the Alexandrite
(757nm) only or
alternating the laser light output of both wavelengths. In an embodiment,
selection will be
accomplished via RS232 commands from the UOA.
[00420] In an embodiment, the time between wavelength changes will
preferably be less
than 0.05 seconds, and the time delay to initiate the response to a wavelength
change shall be less
than 0.01 seconds (which is included in the 0.05 seconds to change
wavelengths). This would
allow a command to be 0.01 seconds before the actual wavelength change is
made. These timing
parameters will permit the device 100 to be capable of alternating the
wavelength output at a rate
up to 20 times per second so as to interleave each separate wavelength
operating at 10 pulses per
second.
[00421] In an embodiment, the laser output pulse width for the Nd:YAG
laser is
approximately 7ns but as long as practical, and in any case should be less
than 25 ns for the best
pulse stability. The laser output pulse width for the Alexandrite laser may be
less than
approximately 60 ns and more preferably less than approximately 50 ns. In an
embodiment, no
satellite pulse (a secondary laser pulse occurring shortly after the primary
pulse) is allowed for
either laser. As discussed above, in an embodiment, one or more light sources
other than the
Nd:YAG or Alexandrite lasers may be employed. Thus, for example, in an
embodiment, one
quickly tunable laser could be deployed to create two or more separate
wavelengths in sequential
light pulses during operation of the device.
[00422] The pulse rate may be operator selectable. In an embodiment, the
pulse rate is
operator selectable from 2, 5, 10 PPS for each wavelength, and when interlace
is selected the
pulse rate will double to 4, 10, 20 PPS. In an embodiment, the maximum time to
select between
pulse rates will be 10 seconds. The pulse rate for each laser wavelength will
be independent of
single wavelength or interlace operation.
[00423] In an embodiment, the energy per pulse (laser output) that will be
directed into the
fiber bundle will be variable between 25 mJ to 250 mJ in a minimum of 15 steps
for each
wavelength. In an embodiment, the control will be via the RS232 port. Energy
per pulse will be
independently adjustable for each wavelength. In an embodiment, the maximum
time for the
output energy to be affected post selection will be approximately 2 seconds.
[00424] It is desirable to minimize the unintended pulse-to-pulse
variation. Accordingly,
in an embodiment, the (uncontrolled) pulse-to-pulse energy variation will be
less than 3% RMS
from the output of either laser after 50 laser pulses.
- 139 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
[00425] In an embodiment, a measure of the output energy of each pulse
(both
wavelengths) will be made and will be communicated with an analog output pulse
to the UOA.
In an embodiment, the pulse will be a stretched representation of the
optically detected pulse.
The amplitude will be a representation of the energy of each output pulse. In
an embodiment, the
amplitude will be 0 to 5 V peak with 5V peak equal to the maximum energy
expected. In an
embodiment, the driver for these signals may be DC coupled throughout and
drive a 1000 ohm
termination with 0 to 5 Volts. In an embodiment, the pulse may be peak
detected and stretched
by at least 200 ns but the peak must occur before 2 us to permit, that at
least two samples are
captures, when employing a 6.8 MHz anti aliasing filter at 20 M samples/sec.
In an embodiment,
a 20 M samples/sec sampling unit is located in the UOA electronics. Interface
connectors may
use BNC on the laser subsystem. The connector output can be provided on either
a single BNC
connector or a pair of BNC connectors,
[00426] In an embodiment, each rising edge of the laser pulses will be
detected and
communicated to the UOA in a TTL format over a coax cable with a BNC
connector. In an
embodiment, separate signals, coax cables and connector may be used for each
additional
wavelength. In an embodiment, the signal will be a positive going TTL signal
that will have a
duration of at least 1 microsecond. In an embodiment, the UOA termination will
be AC coupled
into 50 Ohms.
[00427] In an embodiment, there will be a sync pulse jitter test. The test
may use an
oscilloscope with the trigger using the TTL sync pulse. The input will be the
output of a
wideband optical test detector that is sampling the output of the laser pulse.
The RMS jitter of the
optical detected waveform is preferably less than about 6 ns.
[00428] In an embodiment, each detected optical pulse for each wavelength
is made
available at two test connectors external to the laser system. In an
embodiment, the test
connectors will be BNC connectors, and the drivers for the signals should be
able to drive a 50
Ohm scope load. These test signals may be used to support system testing and
evaluation. In an
embodiment, there is a separate output for each wavelength from the sync
detectors to an analog
driver for a 50 ohms output load -- the amplitude can be a percentage of the
actual pulse out of
the optical detector.
[00429] In an embodiment, a fiber optical bundle interfaces to the output
of the combined
laser output port. In an embodiment, the optical output will be horizontal at
the front-right of the
- 140 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
optical unit. A quick disconnect connector may to be used to connect the fiber
bundle to the laser
output port.
[00430] In an embodiment, the mount for the fiber cable provides self-
alignment to the
laser energy output. In an embodiment, a ceramic disk with a 6 mm centered
aperture will be
installed at the output of the fiber optic mount to minimize damage to the
fiber bundle. In an
embodiment, a micro switch is engaged when the fiber bundle has made
connection. The micro
switch functions as a safety interlock and is used to ensure that the laser
cannot be fired unless
the micro switch is closed.
[00431] In an embodiment, the laser output beam shape will be circular. In
an
embodiment, the beam profile will be flattened to approximate a top hat shape
to ensure
homogeneous illumination of the optical fiber. In an embodiment, the beam
width will be 6 mm
in diameter at the 10% level. For safety and consistency, the beam shape
should not substantially
deviate from this shape; in an embodiment, the beam shape does not deviate
from this shape by
more than 3% RMS over time and from pulse-to-pulse.
[00432] In an embodiment, the output of each laser will be approximately
6.25 mm onto
the fiber optics, and the beam should not have hot spot(s), including after
extensive use. In an
embodiment, both beam shapes (for the Nd:YAG and the Alexandrite) will be
equal in diameter
to within 5% of the 6 mm diameter. For the purposes herein, a hot spot is
defined as a 15%
variation in energy density over any 2 mm segment of the beam cross section.
In an embodiment,
the laser beam must be aimed at the output connector such that 98% of the
output energy is
transmitted into the fiber cable. In an embodiment, a mechanism is provided
for achieving laser
beam alignment in the field.
[00433] In an embodiment, the laser spectral width will be less than 30 nm
at the FWHM
(Full Wave Half Maximum) level, and the spectral characteristics are
preferably stable and do
not vary from pulse-to-pulse by more than 3 nm RMS.
[00434] In an embodiment, the major operating modes of the clinical device
100 are:
a. Off mode: where all power has been turned off and no current
should be flowing
within the laser subsystem. This can be accomplished by turning OFF the main
circuit breaker or by turning the power key switch to off In this case power
may
still be connected to the isolation transformer.
- 141 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
b. Sleep mode or ultrasound only mode: Almost all power is shut down for all
operations but with sufficient energy to place the laser subsystem into the
"on"
mode. For example only the laser control unit is power up.
c. On Mode: Warm Up Period: Places all necessary power ON to allow the laser
to
be warmed up. The laser will measure and report to the UOA the laser head
temperature. Once the laser head temperature has reached a pre determined
value
the UOA will place the laser system into the "standby mode". In an embodiment,
the laser subsystem will not be allowed to go into the "standby mode" until
sufficient warm up has occurred.
d. Standby Mode: Allows the laser to be placed into the "ready mode" quickly
from
a Ready Mode command.
e. Ready Mode: Places the laser into the emission mode but the shutter remains
closed. In an embodiment, the emission mode can be started a pre-specified
interval, e.g., within 1 second or after 20 pulses, after the emission mode
command.
f. Emission mode: Provides specified output energy for as long as this mode is
commanded. In this mode the laser provides for its lamp sync and driver, the Q-
Switch delay and driver and the pulse rate as determined from external
command.
The wavelength output will be as determined from external command.
[00435] In an embodiment, the laser subsystem will have the capability to
go from any
operating mode to any lower operating mode directly: "off' being the lowest
operating mode and
"emission" being the highest operating mode. For example, in an embodiment,
the operator will
be able to go from the emission mode to the standby, on, sleep or off mode
directly. Preferably,
the operator will not be able to go from off to emission directly without
first going through the
modes between.
[00436] In an embodiment, the laser will operate with internal synchronism
and the UOA
will derive its synchronism from the laser via it sync signal outputs. In an
embodiment, time
sensitive interfaces (synchronism signals) will be interfaced using TTL
signals, while computer
interface information will be via R5232 interface. In an embodiment, the
wavelength selection
mode (single YAG, single ALEX, interlace mode) will be selected via R5232 and
the control
unit will produce the internal commands in interlace or single mode with the
right timing. In an
- 142 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
embodiment, electronics will validate the present laser emission thru energy
photodiode and/or
sync pulses and/or Q-Switch TTL sync outputs.
[00437] In an embodiment, a shutter will open to allow laser light to be
emitted (defined as
the emission mode). In an embodiment, the shutter will remain closed unless
two conditions
exist -- a foot switch closure and an RS-232 command. But, as long as the foot
switch remains
closed and an RS232 command exists the emission will exist. Both the foot
switch closure and
the RS232 must both be present to achieve emissions. The foot switch closure
may provide
within the switch a double contact, NC and NO using a three-wire interface as
shown in Figure
31. When either or both the foot switch and RS232 command is changed emission
will cease to
exist via a closure of the shutter, preferably within about 0.5 seconds. The
laser subsystem may
remain in the Ready mode until commanded otherwise.
[00438] In an embodiment, the laser operating system shall keep a non-
volatile time-
stamped record of error codes, of lamp shots, and operational events, for the
purpose of
accountability and troubleshooting. The non-volatile record may be readable,
and possibly
erasable, via RS-232 commands. In an embodiment, erasure of the non-volatile
record requires a
password or other access device. In an embodiment, a log consisting of not
less than 50 events
may be sufficient. In an embodiment, the UOA can poll the number of messages
and read them.
[00439] In an embodiment, the laser subsystem will monitor the temperature
of the lasers
heads and report each to the UOA on a periodic basis, permitting the UOA to
avoid instructing
the laser to go into the Ready Mode unless the laser head has reached an
acceptable temperature,
and automatically placing the laser subsystem into the off mode if the
temperature is
unexpectedly outside of its appropriate operating range.
[00440] In an embodiment, wires to pockels cell and all internal high
radiated signals
should be shielded. To mitigate electromagnetic radiation during the imaging
time of the clinical
device 100, the lamp driver recharging should be delayed by more than 70
microseconds after the
Q-Switch. See Figure 16. During recharge the electromagnetic radiation must be
sufficiently low
so as not to interfere with ultrasound or OA imaging.
[00441] In an alternative embodiment, a control signal can be used to
suppress power
supply switching noise during OA data acquisition, and also during US data
acquisition. For
example, a TTL trigger from within the laser circuitry may be generated such
that a logic HIGH
would cause the internal switching power supply to stop its internal
oscillator that drives the
switching PWM (pulse width modulation) circuitry that powers the flash lamp
circuits, and/or
- 143 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
any other switching operation, and when at a logic LOW would resume normal
operation. In an
embodiment, this control may not be asserted for more than certain ON time
(e.g., 100
microseconds), and to not exceed a certain duty cycle. In an embodiment, a
trigger signal could
be negative logic wherein a logic LOW would stop the oscillator and a logic
HIGH would allow
it to resume. In an embodiment, the trigger signal can be applied to one or
more other switching
power supplies within the laser and./or elsewhere in the OA system, which may
suppress
electrical noise from the power supply during the non-oscillatory interval. In
an embodiment, the
data acquisition period should be within the interval during which the one or
more switching
power supplies have the switching circuitry inhibited. Even where a switching
power supply is
of a type that is not PWM controlled, the trigger can in any event be used to
inhibit operation of
the internal oscillator used to control the switching functions.
[00442] In an embodiment, the user interface console will contain a "Panic
Button" to
place the laser into the off mode by removing all AC power to the laser
system.
[00443] In an embodiment, the laser subsystem and all other subsystems
will operate from
230 +1- 10% VAC, single phases, 60/50 +/-3 Hz, 4000 VA max. In an embodiment,
the mains
voltage may be isolated from the various subsystems by the use of an isolation
transformer such
as part number 925.1202, manufactured by www.toroids.com, or equivalent, and
protected with a
switchable AC circuit breaker on the primary side. The secondary side of this
transformer will
provide AC power to each of the four (4) AC powered subsystems through a soft
start isolation
transformer to avoid inrush current problems. In an embodiment, the laser
subsystem is adapted
to accommodate a sudden loss of input power or brownout without causing
damage, requiring
realignment, tuning or causing unsafe operations.
[00444] In an embodiment, all operating system controls may be provided
via UOA
electronics.
[00445] The present system and methods are described above with reference
to block
diagrams and operational illustrations of methods and devices comprising an
optoacoustic probe.
It is understood that each block of the block diagrams or operational
illustrations, and
combinations of blocks in the block diagrams or operational illustrations, may
be implemented
by means of analog or digital hardware and computer program instructions.
These computer
program instructions may be provided to a processor of a general purpose
computer, special
purpose computer, ASIC, FPGA or other programmable data processing apparatus,
such that the
instructions, which execute via the processor of the computer or other
programmable data
- 144 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
processing apparatus, implements the functions/acts specified in the block
diagrams or
operational block or blocks. In some alternate implementations, the
functions/acts noted in the
blocks may occur out of the order noted in the operational illustrations. For
example, two blocks
shown in succession may in fact be executed substantially concurrently or the
blocks may
sometimes be executed in the reverse order, depending upon the
functionality/acts involved.
[00446] As used in this description and in the following claims, "a" or
"an" means "at least
one" or "one or more" unless otherwise indicated. In addition, the singular
forms "a", "an", and
"the" include plural referents unless the content clearly dictates otherwise.
Thus, for example,
reference to a composition containing "a compound" includes a mixture of two
or more
compounds.
[00447] As used in this specification and the appended claims, the term
"or" is generally
employed in its sense including "and/or" unless the content clearly dictates
otherwise.
[00448] The recitation herein of numerical ranges by endpoints includes
all numbers
subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4,
and 5).
[00449] Unless otherwise indicated, all numbers expressing quantities of
ingredients,
measurement of properties and so forth used in the specification and claims
are to be understood
as being modified in all instances by the term "about," unless the context
clearly dictates
otherwise. Accordingly, unless indicated to the contrary, the numerical
parameters set forth in
the foregoing specification and attached claims are approximations that can
vary depending upon
the desired properties sought to be obtained by those skilled in the art
utilizing the teachings of
the present invention. At the very least, and not as an attempt to limit the
scope of the claims,
each numerical parameter should at least be construed in light of the number
of reported
significant digits and by applying ordinary rounding techniques. Any numerical
value, however,
inherently contains certain errors necessarily resulting from the standard
deviations found in their
respective testing measurements.
[00450] Those skilled in the art will recognize that the methods and
systems of the present
disclosure may be implemented in many manners and as such are not to be
limited by the
foregoing exemplary embodiments and examples. In other words, functional
elements being
performed by single or multiple components, in various combinations of
hardware and software
or firmware, and individual functions, may be distributed among software
applications at either
the client level or server level or both. In this regard, any number of the
features of the different
embodiments described herein may be combined into single or multiple
embodiments, and
- 145 -
CA 02902222 2015-08-20
WO 2014/144257 PCT/US2014/028587
alternate embodiments having fewer than, or more than, all of the features
described herein are
possible. Functionality may also be, in whole or in part, distributed among
multiple components,
in manners now known or to become known. Thus, myriad
software/hardware/firmware
combinations are possible in achieving the functions, features, interfaces and
preferences
described herein. Moreover, the scope of the present disclosure covers
conventionally known
manners for carrying out the described features and functions and interfaces,
as well as those
variations and modifications that may be made to the hardware or software or
firmware
components described herein as would be understood by those skilled in the art
now and
hereafter.
[00451] Furthermore, the embodiments of methods presented and described as
flowcharts
in this disclosure are provided by way of example in order to provide a more
complete
understanding of the technology. The disclosed methods are not limited to the
operations and
logical flow presented herein. Alternative embodiments are contemplated in
which the order of
the various operations is altered and in which sub-operations described as
being part of a larger
operation are performed independently.
[00452] Various modifications and alterations to the invention will become
apparent to
those skilled in the art without departing from the scope and spirit of this
invention. It should be
understood that the invention is not intended to be unduly limited by the
specific embodiments
and examples set forth herein, and that such embodiments and examples are
presented merely to
illustrate the invention, with the scope of the invention intended to be
limited only by the claims
attached hereto. Thus, while the invention has been particularly shown and
described with
reference to a preferred embodiment thereof, it will be understood by those
skilled in the art that
various changes in form and details may be made therein without departing from
the spirit and
scope of the invention.
- 146 -
