Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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METHODS AND DEVICES FOR IMPROVING
BROADBAND ULTRASONIC ATTENUATION AND
SPEED OF SOUND MEASUREMENTS
S TECHNICAL FIELD
The invention relates to ultrasonic methods, compositions and devices,
particularly methods, compositions and devices that provide for reproducible
positioning of the ultrasonic transducers) over an anatomical region using
anatomical
landmarks and soft tissue correction.
BACKGROUND
Ultrasonic techniques have recently been introduced as methods free of
ionizing
radiation for non-invasive assessment of skeletal status in patients with
osteoporosis.
Quantitative aspects of these ultrasonic techniques can permit assessment of
bone mass
1 S and density, as well as bone structure. Ultrasonic techniques for
evaluating skeletal
status also include measurements of speed of sound ("SOS") that reflect the
transmission velocity of ultrasonic waves passing through bone tissue and soft
tissue,
measurements of broadband ultrasonic attenuation ("BUA") that assess the
frequency
dependence of ultrasonic attenuation, and pulse echo techniques that measure
the energy
scattered from the internal structure of the bone.
Many different measurement sites have been proposed for osteoporosis, such as
the tibia, the patella, the phalanges, or the calcaneus. The calcaneus is
preferred for
quantitative ultrasonic measurements of skeletal status. It is composed of
predominantly
trabecular bone with only a thin cortical bone envelope medially and
laterally, which
2S together provide an excellent medium for detecting changes in SOS and BUA
measurements. The calcaneus also permits convenient ultrasonic interrogation
for the
operator and the patient alike.
Although a number of commercial devices exist for diagnosis of osteoporosis,
clinicians have recognized the limitations of such devices and methods.
Correlations
between quantitative ultrasonic measurements and assessments of bone mineral
density
using quantitative computed tomography, dual x-ray absorptiometry, and single
photon
absorptiometry have been reported to be poor at the calcaneus, as well as at
other sites.
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Consequently, the inventors have recognized the need, among other things, to
provide reliable ultrasonic devices and accurate, and qualitative or
quantitative methods
for ultrasonic measurements in the diagnosis of osteoporosis, as well as
methods and
devices to generally improve diagnostic tools based on ultrasonic
measurements.
The present invention recognizes for the first time that errors arising from
misplacement of interrogation sites in ultrasonic measurements of speed of
sound and
broadband ultrasonic attenuation of the ankle bone can be corrected by
positoning the
transducers) with respect to an anatomical landmark. Previously, it was not
recognized
that BUA or SOS measurements could be improved by compensating for positioning
errors introduced by soft tissues, growth of the ankle, or interindividual
size differences.
Nor was it recognized that changes in ankle shape, soft tissue or position are
a potential
source of decreased accuracy and reproducibility of SOS and BUA measurements
in
patients with peripheral edema undergoing diuretic or other types of medical
treatment
of edema with resultant fluctuations in soft tissue thickness. The present
invention
includes positioning the ankle using A-scan or B-scan technology to identify
anatomical
locations used for measuring SOS and BUA.
The invention provides for an improved ultrasonic system for tissue BUA or
SOS interrogation of a heel, comprising: a) a first ultrasonic transducer with
an axis of
transmission in common with a second ultrasonic transducer, wherein the axis
of
transmission is through a portion of tissue of a heel, b) an x, y positioner
that engages a
first ultrasonic transducer and a second ultrasonic transducer, the x, y -
positioner
controllably positions the first ultrasonic transducer and the second
ultrasonic transducer
in a desired manner between at least a first and a second position while
generally
maintaining the axis of transmission, and c) a computational unit designed to
manage
ultrasonic signal transmission and reception of the first ultrasonic
transducer and the
second ultrasonic transducer. Typically, the computational unit generates an
anatomical
landmark from either an A-scan or B-scan in order to direct BUA and SOS
measurements. The ultrasonic system may also include a computational unit that
can
identify an anatomical landmark in the heel and direct the x, y positioner to
a position
over the anatomic landmark, and thereby positioning the first ultrasonic
transducer and
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second ultrasonic transducer to have an axis of transmission generally through
the
anatomical landmark in the heel.
In another embodiment, the invention includes an ultrasonic system for
automated ultrasonic identification of an anatomical landmark in the heel,
comprising:
a) an ultrasonic transducer unit comprising a pair of ultrasonic transducers
where a first
member of the pair is designed to transmit signals and a second member of the
pair is
designed to receive signals, and b) a computational unit designed to manage
ultrasonic
signal transmission and reception of the ultrasonic transducer unit for BUA
and SOS
measurements in the heel and to process signals to identify an anatomical
landmark in
the heel in either a A scan or B-scan mode or both. The ultrasonic system can
further
comprise a positioning unit for changing the spatial relationship between the
anatomic
landmark in the anatomical region and the ultrasonic transducer unit, thereby
permitting
interrogation with reference to the anatomical landmark in, the heel by
positioning the
transducer unit with respect to the anatomical landmark.
In another embodiment, the invention includes an ultrasonic method for
generating an anatomic landmark for ultrasonic interrogation of a heel,
comprising:
positioning, with respect to an anatomical region of a heel, an ultrasonic
transducer unit
comprising a pair of ultrasonic transducers where a first member of the pair
is designed
to transmit signals and a second member of the pair is designed to receive
signals,
interrogating the anatomical region with the ultrasonic transducer unit,
identifying an
anatomical landmark in the anatomical region with an ultrasonic property of
the heel,
and storing the anatomic landmark in a storage device. The ultrasonic method
may
include' the--Steps-- of comparing the. location of the ultrasonic-transducer
unit to the
location of the anatomical landmark in the heel and positioning the ultrasonic
transducer
unit at a preselected or desired set of coordinates in relation to the
anatomical landmark
of the heel.
While many of the embodiments of the invention will find particular
application
in clinical measurements, such as BUA or SOS, and surgical procedures, such
trocar
procedures and catheter procedures, the invention provides for general
ultrasonic
devices and methods that will be applicable to many clinical applications.
The invention provides for an improved ultrasonic system for tissue ultrasonic
interrogation, comprising: a) a first ultrasonic transducer with an axis of
transmission in
common with a second ultrasonic transducer, wherein the axis of transmission
is
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through a portion of tissue, b) an x, y positioner that engages the first
ultrasonic
transducer and the second ultrasonic transducer, the x, y positioner
controllably
positions the first ultrasonic transducer and the second ultrasonic transducer
in a desired
manner between at least a first and a second position while generally
maintaining the
axis of transmission, and c) a computational unit designed to manage
ultrasonic signal
transmission and reception of the first ultrasonic transducer and the second
ultrasonic
transducer in either A scan or B scan mode or both and may optionally be
designed to
control movement of the x, y positioner. The ultrasonic system can further
comprise a z
positioner that positions at least one of the first or second ultrasonic
transducers, and the
z positioner changes the distance of transmission along the axis of
transmission between
the first ultrasonic transducer and the second ultrasonic transducer. The
ultrasonic
system may include a computational unit that can identify an anatomic landmark
in an
interrogated tissue and direct the x, y positioner to a position over the
anatomic
landmark, and thereby positioning the first ultrasonic transducer and second
ultrasonic
transducer to have an axis of transmission generally through the anatomic
landmark.
In another embodiment, the invention includes an ultrasonic system for
automated ultrasonic identification of an anatomical landmark, comprising: a)
an
ultrasonic transducer unit comprising either 1 ) a first ultrasonic transducer
that can
transmit and receive signals or 2) a pair of ultrasonic transducers where a
first member
of the pair is designed to transmit signals and a second member of the pair is
designed
to receive signals, and b) a computational unit designed to manage ultrasonic
signal
transmission and reception of the ultrasonic transducer unit and to process
signals to
-identify an anatomical landmark--in an anatomical region in either a A scan
or B scan-----.-. -- .--.- -
mode or both. The ultrasonic system can further comprise a positioning unit
for
changing the spatial relationship between the anatomic landmark in the
anatomical
region and the ultrasonic transducer unit, thereby permitting interrogation
with
reference to the anatomic landmark in the anatomical region by positioning the
transducer unit with respect to the anatomical landmark.
In another embodiment, the invention includes an ultrasonic method for
generating an anatomic landmark for ultrasonic interrogation, comprising:
positioning,
with respect to an anatomical region, an ultrasonic transducer unit comprising
either 1 ) a
first ultrasonic transducer that can transmit and receive signals or 2) a pair
of ultrasonic
transducers where a first member of the pair is designed to transmit signals
and a second
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member of the pair is designed to receive signals, interrogating the
anatomical region
with the ultrasonic transducer unit, identifying an anatomic landmark in the
anatomical
region with an ultrasonic property of the anatomical region, and storing the
anatomic
landmark in a storage device. The ultrasonic method may include the steps of
S comparing the location and axis of transmission of the ultrasonic transducer
unit to the
location of the anatomic landmark and positioning the ultrasonic transducer
unit to
produce an axis of transmission at a preselected or desired set of coordinates
in relation
to the anatomic landmark.
In another embodiment, the invention includes an ultrasonic method for
generating an anatomic landmark for ultrasonic interrogation of an anatomical
region,
comprising: a) positioning, if necessary, on the surface of a patient, with
respect to an
anatomical region, an ultrasonic transducer unit comprising either 1) a first
ultrasonic
transducer that can transmit and receive signals or 2) a pair of ultrasonic
transducers
wherein a first member of the pair is designed to transmit signals and a
second member
of the pair is designed to receive signals, b) interrogating the anatomical
region with the
ultrasonic transducer unit at a first transmission angle, c) interrogating the
anatomical
region with the ultrasonic transducer unit at a second transmission angle, and
d)
identifying an anatomic landmark in common with the signals obtained in steps
(b) and
(c) in the anatomical region with an ultrasonic property of the anatomical
region. The
ultrasonic method may include the step of storing the anatomic landmark in a
storage
device. The positioning step may also include positioning the transducer unit
at a
plurality of predetermined transmission angles for interrogation. Typically,
the use of a
second transmission angle increases the accuracy of the anatomical landmark
compared. _- .-
to interrogation with a single transmission angle.
In another embodiment, the invention includes a computer program product,
comprising:
a) instructions for a positioning unit to position a transducer or plurality
of
transducers at a plurality of interrogation sites in an anatomical region,
b) instructions for interrogating the anatomical region with the transducer or
the plurality of transducers at the plurality of interrogation sites,
c) instructions for generating a map of the anatomical region using
ultrasonic measurements from the plurality of interrogation sites,
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d) instructions for the positioning unit to position the
transducerinstructions
or the plurality of transducers at a second plurality of interrogation sites
in the
anatomical region if the map lacks sufficient features to be clinically
relevant for a
clinically relevant measurement,
e) instructions for interrogating the anatomical region for a clinically
relevant instructions measurement;
wherein instructions (a) through (e) permit the generation of the map which
facilitates a clinically relevant measurement and instructions (a) through (e)
are stored
on a computer retrievable medium. The computer program product can also
include
instructions for comparing the map with a reference map of substantially the
same
anatomical region using predefined criteria, the predefined criteria
optionally
comprising percent similarity of contours of bones, percent similarity of an
anatomical
landmark or percent similarity of reflective surfaces; instructions for
interrogating the
anatomical region for a clinically relevant measurement if the map matches the
reference map; and instructions for the positioning unit to position the
transducer or the
plurality of transducers at a second plurality of interrogation sites in the
anatomical
region if the map lacks sufficient features to be clinically relevant for a
clinically
relevant measurement.
The methods and devices provided also herein permit, among other things,
correction of ultrasonic parameters, such as speed of sound and broadband
ultrasonic
attenuation, for soft tissue interposed in the ultrasonic beam.
The invention also provides for an improved ultrasonic system for BUA or SOS
- - measurements- in a heel using soft -tissue correction: - The- s-ystem can
include a first - -- - -- -- .- -----
ultrasonic transducer with an axis of transmission in common with a second
ultrasonic
transducer. The axis of transmission is designed to pass through a portion of
tissue
from a heel. Soft tissue is usually measured using A scan or B scan.
Preferably, soft
tissue thickness greater than about 1 cm can be detected within about 3 mm of
the actual
layer thickness. Estimates of soft tissue can be used to correct BUA or SOS
measurements. The system can include an x, y positioner that engages the first
ultrasonic transducer and the second ultrasonic transducer and is adapted to
accommodate the heel. Typically, the x, y positioner controllably positions
the first
ultrasonic transducer and the second ultrasonic transducer in a desired manner
between
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at least a first and a second position while generally maintaining the axis of
transmission.
The system includes a computational unit designed to manage 1) ultrasonic
signal transmission and reception of the first ultrasonic transducer and the
second
ultrasonic transducer and 2) soft tissue correction of BUA or SOS
measurements. It
may optionally be designed to control movement of the x, y positioner. The
system
offers the advantage of improving BUA and SOS measurements by the soft tissue
correction compared to the absence of soft tissue correction. The
computational unit
can include instructions to estimate broadband ultrasonic attenuation (or SOS)
in the
heel and correct the broadband ultrasonic attenuation (or SOS) for soft tissue
present in
the heel. The computational unit can also comprise a database of correction
factors for
soft tissue thicknesses and broadband ultrasonic attenuation or speed of
sound. The
computational unit can also include instructions to calculate soft tissue
thickness.
In another embodiment, the invention provides for an ultrasonic system for
soft
tissue correction for BUA or SOS measurements in a heel. The system includes
an
ultrasonic transducer unit comprising a pair of ultrasonic transducers for
either BUA or
SOS measurements where a first member of the pair is designed to transmit
signals and
a second member of the pair is designed to receive signals. The system
includes a
computational unit designed to manage ultrasonic signal transmission and
reception of
the ultrasonic transducer unit and to correct BUA or SOS measurements for the
presence of soft tissue in an anatomical region of a heel. The computational
unit can be
designed to process ultrasonic signals received from the ultrasonic transducer
unit to
generate-an estimate-of.saft.tissue in the anatomical region;-and to correct
the BUA or
SOS measurement. Preferably, the computational unit is further designed to
process
received ultrasonic signals from an ultrasonic transducer to generate at least
one data set
of an ultrasonic property to estimate soft tissue thickness. Typically, the
ultrasonic
property measures soft tissue thickness from bone to skin.
The invention also includes an ultrasonic method for determining broadband
ultrasonic attenuation or speed of sound measurements in a heel of a human in
need of
diagnosis of osteoporosis, comprising:
a) interrogating a tissue of the heel with an ultrasonic transducer unit
adapted for
either 1) broadband ultrasonic attenuation or 2) speed of sound measurements
or
both,
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b) interrogating the tissue with an ultrasonic transducer to determine soft
tissue
thickness in a heel, and
c) determining dense tissue broadband ultrasonic attenuation, dense tissue
speed of
sound or both by correcting for the soft tissue thickness,
wherein the determining step generates a dense tissue broadband ultrasonic
attenuation value, dense tissue speed of sound value or both that is more
indicative
of broadband ultrasonic attenuation or speed of sound in dense tissue than in
the
absence of correcting for soft tissue thickness.
The invention also includes an ultrasonic method for correcting for soft
tissue
interposed between ultrasonic transducers in a heel of a human in need of
broadband
ultrasonic attenuation or speed of sound measurements, comprising:
a) interrogating a tissue of the heel with an ultrasonic transducer unit
adapted for
either 1 ) broadband ultrasonic attenuation or 2) speed of sound measurements
or
both,
b) interrogating the tissue with an ultrasonic transducer to determine soft
tissue in
an anatomical region in a heel with the ultrasonic transducer, and
c) determining dense tissue broadband ultrasonic attenuation, dense tissue
speed of
sound or both by correcting for the soft tissue,
wherein the determining step generates a dense tissue broadband ultrasonic
attenuation
value, dense tissue speed of sound value or both that is more indicative of
broadband
ultrasonic attenuation or speed of sound in dense tissue of the heel than in
the absence
of correcting for soft tissue.
The invention also includes a computer program-product; comprising:
a) instructions for interrogating an anatomical region of a heel with a
transducer
unit at an interrogation site for soft tissue in a heel,
b) instructions for generating an estimate of soft tissue of the anatomical
region
using ultrasonic measurements from the interrogation site,
c) instructions for interrogating the anatomical region for a clinically
relevant BUA
and SOS measurement;
wherein instructions (a) through (c) permit the generation of an estimate of
soft
tissue that facilitates a clinically relevant BUA or SOS measurement and
instructions (a) through (c) are stored on a computer retrievable medium.
Computer
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programs of the invention can include instructions to perform the methods and
operation of devices described herein.
While many of the embodiments of the invention will find particular
application
in clinical measurements, such as BUA or SOS, and surgical procedures, such
trocar
procedures and catheter procedures, the invention also provides for general
ultrasonic
devices and methods relating to multiple transmission angle ultrasonic
interrogation in
tissues that will be applicable to many clinical applications.
The invention includes an ultrasonic system for multiple transmission angle
ultrasonic interrogation in tissues with heterogenous structures that alter
ultrasonic
properties. The system can comprise a first ultrasonic transducer with an axis
of
transmission in common with a second ultrasonic transducer, said axis of
transmission
is through a portion of tissue suspected of having heterogenous structures
that alter
ultrasonic properties. The system can include an x, y positioner that can
engage the first
ultrasonic transducer and the second ultrasonic transducer. The x, y
positioner
controllably 1) positions the first ultrasonic transducer and the second
ultrasonic
transducer in a desired manner between at least a first and a second position
while
generally maintaining the axis of transmission and 2) establishes
predetermined
transmission angles for the first ultrasonic transducer and the second
ultrasonic
transducer to interrogate the portion of the tissue at multiple transmission
angles
through heterogenous structures in the tissue. A computational unit can be
included
that is designed to manage ultrasonic signal transmission and reception of the
first
ultrasonic transducer and the second ultrasonic transducer with either BUA or
SOS or
-.--both. It may optionally-be designed to control movement of the x, y
positioner. The
ultrasonic measurements with multiple transmission angles are typically
improved
compared to interrogation in the absence of multiple transmission angles.
In addition, the invention includes an ultrasonic system for automated
ultrasonic
measurements at multiple transmission angles. The system comprises an
ultrasonic
transducer unit comprising 1 ) an ultrasonic transducer that can transmit and
receive
signals and 2) a multiple transmission angle positioner to vary the
transmission angle of
the ultrasonic transducer with respect to the plane of a tissue in a
predetermined fashion.
Preferably, the transducer unit is designed to vary the transmission angle
without
necessarily changing the general position of the ultrasonic transducer with
respect to the
tissue. This allows the substantially same region to be interrogated at
different angles.
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The system can include a computational unit designed to manage ultrasonic
signal
transmission and reception of the ultrasonic transducer unit and to process
signals from
the ultrasonic transducer unit at multiple transmission angles, for example
using signal
averaging, filtering unwanted signals or pattern recognition of desired types
of acoustic
5 signatures. Preferably, the computational unit is designed to process
received ultrasonic
signals from the ultrasonic transducer to generate at least one data set of an
ultrasonic
property determined at predetermined, multiple transmission angles. Such an
ultrasonic
property can be selected from the group consisting of broadband ultrasonic
attenuation,
echogenicity, reflective surfaces, distances from the transducer unit, speed
of sound, and
10 ultrasonic images.
In addition, the invention includes an ultrasonic system for tissue ultrasonic
interrogation for broadband ultrasonic attenuation at multiple transmission
angles. The
system comprises a first ultrasonic transducer with an axis of transmission
through an
anatomical region to be interrogated and the first ultrasonic transducer is
adapted for
BUA and a second ultrasonic transducer adapted for BUA with the axis of
transmission
through the anatomical region to be interrogated, wherein monitoring broadband
ultrasonic attenuation between the first ultrasonic transducer and the second
ultrasonic
transducer is permitted. The system includes a positioning unit to vary the
transmission
angle of the axis of transmission with respect to the tissue plane. The system
may have
a computational unit designed to manage ultrasonic signal transmission of the
first
ultrasonic transducer, to manage ultrasonic signal reception of the second
ultrasonic
transducer and to control the transmission angle of the axis of transmission.
Typically,
-- the positioning unit comprises- an x, y positioner for the first -
ultrasonic transducer-and
the second ultrasonic transducer that can establish at least 3 predetermined
transmission
angles while maintaining a common axis of transmission. Preferably, the x, y
positioner
is designed to position the first ultrasonic transducer and the second
ultrasonic
transducer with first axis of transmission at each transmission angle
generally passing
through the same anatomical region. Typically, the center of axis of
transmission at
each angle passes through an area of the anatomical region that is no more
than about 5
to 8 cm squared.
The invention also includes an ultrasonic method for ultrasonic interrogation
at
multiple transmission angles: The method comprises positioning, with respect
to an
anatomical region, an ultrasonic transducer unit comprising either 1 ) a first
ultrasonic
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transducer that can transmit and receive signals or 2) a pair of ultrasonic
transducers
where a first member of the pair is designed to transmit signals and a second
member of
the pair is designed to receive signals. The methods includes interrogating
the
anatomical region with the ultrasonic transducer unit at predetermined,
multiple
transmission angles, and recording an ultrasonic property of the anatomical
region. The
method further comprises storing the ultrasonic property in a storage device.
The invention also includes an ultrasonic method for determining broadband
ultrasonic attenuation or speed of sound measurements in dense tissues. The
method
comprises interrogating a tissue at predetermined, multiple transmission
angles with an
ultrasonic transducer unit adapted for either 1) broadband ultrasonic
attenuation or 2)
speed of sound measurements or both. The method includes determining dense
tissue
broadband ultrasonic attenuation, dense tissue speed of sound or both at two
or more
predetermined, multiple transmission angles, wherein the determining step
generates a
dense tissue broadband ultrasonic attenuation value, dense tissue speed of
sound value
or both that is more indicative of broadband ultrasonic attenuation or speed
of sound in
dense tissue than interrogation in the absence of predetermined, multiple
transmission
angles.
The invention also includes an ultrasonic method for generating an anatomic
landmark for ultrasonic interrogation of an anatomical region, comprising:
positioning, if necessary, on the surface of a patient, with respect to an
anatomical region, an ultrasonic transducer unit comprising either 1 ) a first
ultrasonic
transducer that can transmit and receive signals or 2) a pair of ultrasonic
transducers
wherein a-first member- of the pair is designed to transmit signals and a
second--member
of the pair is designed to receive signals, and
interrogating the anatomical region with the ultrasonic transducer unit at a
first
transmission angle,
interrogating the anatomical region with the ultrasonic transducer unit at a
second transmission angle,
identifying an anatomic landmark in common with the signals obtained in the
above steps in the anatomical region with an ultrasonic property of the
anatomical
region.
The invention also includes an ultrasonic method for determining broadband
ultrasonic attenuation or speed of sound measurements in dense tissues,
comprising:
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interrogating a patient's tissue with at least a first ultrasonic transducer
unit at a
first transmission angle and a second ultrasonic transducer unit at a second
transmission
angle, wherein said first ultrasonic transducer unit and said second
ultrasonic transducer
unit are a) adapted for either 1) broadband ultrasonic attenuation or 2) speed
of sound
measurements or both and b) have an angle of least about 150 degrees between
said first
ultrasonic transducer unit and said second transducer unit,
interrogating said patient's tissue with said first ultrasonic transducer unit
at a
third transmission angle and said second ultrasonic transducer unit at a
fourth
transmission angle while maintaining an angle of at least about 150 degrees
between
said first transducer unit and said second transducer unit, and
determining dense tissue broadband ultrasonic attenuation, dense tissue speed
of
sound or both for said tissue; wherein said determining step generates a dense
tissue
broadband ultrasonic attenuation value, dense tissue speed of sound value or
both that is
more indicative of broadband ultrasonic attenuation or speed of sound in dense
tissue
than in the absence of interrogating said patient's tissue with at least said
first ultrasonic
transducer unit at a third transmission angle and said second ultrasonic
transducer unit
at a fourth transmission angle.
The invention also includes an ultrasonic system for determining broadband
ultrasonic attenuation or speed of sound measurements in a tissue, comprising:
a transducer unit comprising at least a first ultrasonic transducer engaged
with a
first multiple transmission angle unit to controllably vary first transmission
angles and a
second ultrasonic transducer engaged with a second multiple transmission angle
unit to
- ---- --eont-rollably vary second transmission angles; -wherein the first
ultrasonic transducer- - - --
unit and the second ultrasonic transducer unit are adapted for either 1 )
broadband
ultrasonic attenuation or 2) speed of sound measurements or both, and
a computational unit for controllably adjusting transmission angles of the
first
and second transducer; wherein the ultrasonic system will measure broadband
ultrasonic
attenuation value, speed of sound value or both if so desired.
The invention also includes a computer program product, comprising:
instructions for a positioning unit to vary the transmission angle of a
transducer
or plurality of transducers at a plurality of transmission angles in an
anatomical region,
instructions for interrogating the anatomical region with the transducer or
the
plurality of transducers at the plurality of transmission angles, and
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instructions for recording at least one ultrasonic property at the plurality
of
transmission angles, wherein the above instructions facilitates a clinically
relevant
measurement and such instructions are stored on a computer retrievable medium.
S BRIEF DESCRIPTION OF FIGURES
FIG. 1 shows one embodiment of the invention relating to methods of
interrogating a tissue, generating an anatomical map or instructing a
positioner to
position a transducer(s). An anatomical map is generated from data by
interrogating the
tissue at a first transducers) positions) (nl), for instance using either A
scan or B scan
or both. A clinical measurement is then made at the first position n~ . The
process of
interrogation, map generation and clinical measurement can be repeated at each
subsequent position (n~, n2, ...). Optionally, the anatomical map can be
compared to a
reference map that is usually stored in computational unit. When a suitable
match
occurs with the reference map interrogation can be initiated.
1S FIG. 2 shows another embodiment of the invention relating to methods of
interrogating a tissue, identifying an anatomical landmark or instructing a
positioner to
position a transducer(s). The transducers) is positioned. An anatomical map is
generated from data by interrogating the tissue at a first transducers)
positions) (nl),
for instance using either A scan or B scan or both. A comparison of the map to
landmark criteria is then made to identify a landmark at the first position
n~. The process
of positioning, inten:ogation, map generation and comparison can be repeated
at each
subsequent position (n~, n2,...). After a landmark has been identified, a
clinical
measurement can-be initiated. _ .
FIG. 3A shows an example demonstrating the influence of soft tissue thickness
2S on ultrasonic measurements of speed of sound. As the thickness of the soft
tissue
interposed in the scan path increases, measured speed of sound, in this
example of the
calcaneus, decreases.
FIG. 3B shows an example demonstrating the results when measured speed of
sound is corrected for thickness of the soft tissue layers interposed in the
scan path.
This correction is typically performed by measuring soft tissue thickness with
A-scan or
B-scan ultrasonics. As the soft tissue thickness increases, corrected speed of
sound does
not change significantly.
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FIG. 4A shows an example demonstrating the influence of soft tissue thickness
on measurements of broadband ultrasonic attenuation. As the thickness of the
soft tissue
interposed in the scan path increases, measured broadband ultrasonic
attenuation values,
in this example of the calcaneus, decrease.
FIG. 4B shows an example demonstrating the results when measured broadband
ultrasonic attenuation is corrected for thickness of the soft tissue layers
interposed in the
scan path. This correction is typically performed by measuring soft tissue
thickness
with A-scan or B-scan ultrasonics. As the soft tissue thickness increases,
corrected
broadband ultrasonic attenuation values do not change significantly.
FIG. 5A shows an example of a typical prior art device for measuring the speed
of sound or broadband ultrasonic attenuation in a healthy non-edematous
patient. The
position of the patient's foot 500, of the calcaneus 510, and of the
ultrasonic
interrogation site 520 are fixed with respect to the device frame 530.
FIG. 5B shows an example of a typical prior art device for measuring the speed
1 S of sound or broadband ultrasonic attenuation in a patient with peripheral
edema. Edema
increases the thickness of the soft tissue inferior and posterior to the
calcaneus. Since
the position of the ultrasonic interrogation site 520 is fixed relative to the
device frame
530, a more inferior and posterior region is measured within the calcaneus 510
when
compared to FIG. 5A that is even partially outside the calcaneus 510.
FIG. 5C shows one embodiment of the invention with a probe for measuring for
example speed of sound or broadband ultrasonic attenuation of the calcaneus,
in this
case in a healthy non-edematous patient. The position of the ultrasonic
interrogation
-- site 520 is not fixed with respect to the device frame 530 but is
determined, for example,
based on landmarks or anatomical maps using A-scan or B-scan ultrasonics.
FIG. 5D shows the same embodiment of the invention as seen in FIG. 5C with
a probe for measuring for example speed of sound or broadband ultrasonic
attenuation
of the calcaneus, in this case in a patient with peripheral edema. Edema
increases the
thickness of the soft tissue inferior and posterior to the calcaneus. Since
the position of
the ultrasonic interrogation site 520 is not fixed relative to the device
frame 530, but is
determined, for example, based on landmarks or anatomical maps using A-scan or
B-
scan ultrasonic, the interrogation site in the calcaneus remains substantially
constant in
the presence of peripheral edema and does not change significantly compared to
conditions illustrated in FIG. 5C.
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FIG. 6A shows another embodiment of the invention with a device for
measuring for example speed of sound or broadband ultrasonic attenuation of
the
calcaneus, in this case in a healthy non-edematous patient. The position of
the patient's
foot 600 and of the calcaneus 610 are not fixed with respect to the device
frame 650.
5 The ultrasonic transducer 620 is, however, attached 630 to the device frame
650. The
foot 600 is placed on a foot holder 640 that can be moved in the x- or y-
direction 660.
The foot 600 and the calcaneus 610 are positioned relative to the ultrasonic
transducer
620 for example based on landmarks or anatomic maps using A-scan or B-scan
ultrasonics.
10 FIG. 6B shows the same embodiment of the invention as demonstrated in FIG.
6A with a probe for measuring for example speed of sound or broadband
ultrasonic
attenuation of the calcaneus, in this case in a patient with peripheral edema.
Since the
position of the foot 600 and of the calcaneus 610 is not fixed relative to the
device
frame 650, but is determined, for example, based on landmarks or anatomical
maps
15 using A-scan or B-scan ultrasonics, the interrogation site of the
ultrasonic transducer
620 at the calcaneus remains substantially constant in the presence of
peripheral edema
and does not change significantly when compared to the condition illustrated
in FIG.
6A.
FIG. 7A shows another embodiment of the invention comprising two ultrasonic
transducers 700 attached to an x-positioner 710 and a y-positioner 720. The
heel 730
and the calcaneus 740 are seated on a foot holder 750. The ultrasonic
transducer 700 is
brought in contact with the heel 730 using a z-positioner member 760 that can
move in
- -and - out of - a frame 770 continuously or in a- stEpwise -fashion. The
ultrasonic
transmission axis 780 is also shown.
FIG. 7B is a side view of the ultrasonic transducer (T) 700, the x-positioner
710,
and the y-positioner 720 shown in FIG. 7A showing the tracks of each
positioner.
Typically, one positioner will engage the other positioner to permit x, y
movement
either concurrently (moving in both directions simultaneously) or sequentially
(moving
in one dimension first and then in a second dimension).
FIG. 7C shows another embodiment of the invention. The ultrasonic transducers
700 are attached to a positioning system 790 that affords movement of the
transducers
in x, y-, and z-direction, as well as angulation of the transducers 700 and
the resultant
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ultrasonic transmission axis 780. The angulation position of the transducers
700 and the
ultrasonic transmission axis 780 is substantially zero.
FIG. 7D shows the ultrasonic transducers 700 attached to a positioning system
790 that affords movement of the transducers in x, y-, and z-direction, as
well as
angulation of the transducers 700 and the resultant ultrasonic transmission
axis 780.
The angulation position of the transducers 700 and the ultrasonic transmission
axis 780
is substantially different from zero.
FIG. 7E shows an expanded view of the embodiment presented in FIGS. 7A-D.
The ultrasonic transducer 700 is attached to a positioning system 790 that
affords
movement of the transducers in x, y-, and z-direction, as well as angulation
of the
transducers 700. The ultrasonic beam 795 has substantially zero angulation.
FIG. 7F shows an expanded view of the positioning system 790 and the
ultrasonic transducers 700 with inferior angulation of the ultrasonic beam
795.
FIG. 7G shows a magnification view of the positioning system 790 and the
ultrasonic transducers 700 with superior angulation of the ultrasonic beam
795.
FIG. 8A is a front view of another embodiment of the invention where the
transducer 800 is moved along an x, y- positioner 810 using electromagnetic
forces
rather than using a mechanical or electro-mechanical x, y-positioner.
FIG. 8B shows a side view of the transducer 800 and the electromagnetic x, y-
positioner 810. The transducer 800 is brought in contact with the heel (not
shown) using
a z-positioner member 820 that is moved in and out of frame 830.
FIG. 8C shows a modification of the embodiment present in FIG. 8B. The
sides of the transducer- 800 are--isolated from the electromagnetic x; y-
positioner 810 -.
using a flexible or movable electromagnetic insulator 840.
FIG. 9A and FIG. 9B show a tissue interrogated by an ultrasonic transducer
(940; T) that transmits to an ultrasonic receiver (950; R) (or detector) at
different
transmission angles and with different axes of transmission. The axis of
transmission is
shown as a (or ~3) and has a transmission path from T to R.
FIG. 9C and FIG. 9D show the same tissue as FIG. 9A and FIG. 9B in a
different physiological state that changes the dimensions of the tissue and
its underlying
structure. The tissue is interrogated by an ultrasonic transducer (940; T)
that transmits
to an ultrasonic receiver (950; R) (or detector) at different transmission
angles and with
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different axes of transmission as in FIG. 9C and FIG. 9D. The axis of
transmission is
shown as a (or (3) and has a transmission path from T to R.
FIG. 9E shows received signals in such tissue in different physiological
states
and at different transmission angles.
DETAILED DESCRIPTION OF THE INVENTION
1.0 ABBREVIATIONS AND DEFINITIONS
ABBREVIATIONS include broadband ultrasonic attenuation (BUA) and speed of
sound (S()S).
Acoustic communication refers to the passage of ultrasonic waves between two
points in a predetermined manner. Usually, this is accomplished by selecting a
desired
pathway between the two points that permits the passage of ultrasonic waves
either
directly or indirectly. Direct passage of ultrasonic waves would occur, for
instance,
when an ultrasonic crystal is directly disposed to (usually touching) an
acoustic
coupling material, such as a composite. Indirect passage of ultrasonic waves
would
occur, for instance, when an ultrasonic crystal is located at a predetermined
distance
from an acoustic coupling material or when a number of acoustic coupling
materials,
often heterogenous materials, form two or more layers.
Acoustic coupler refers to a connection or plurality of connections between an
ultrasonic crystal and a substance that reflects or passes ultrasonic pulses
and is not part
of the device or object being interrogated. The acoustic coupler will permit
passage of
ultrasonic waves. It is desirable for such couplers to minimize attenuation of
ultrasonic
pulses or signals artd-to minimize changes in the physical properties-of an
ultrasonic
wave, such as wave amplitude, frequency, shape and wavelength. Typically, an
ultrasonic coupler will either comprise a gel or other substantially soft
material, such as
a pliable polymer matrix, that can transmit ultrasonic pulses. Alternatively,
an
ultrasonic coupler can be a substantially solid material, such as a polymer
matrix, that
can transmit ultrasonic pulses. An ultrasonic coupler is usually selected
based on its
acoustic impedance match between the object being interrogated and the
ultrasonic
crystal(s). If a reflective surface is desired, for instance as a spatial
marker, a larger
impedance difference is selected compared to situations where it is
advantageous to
minimize a reflective surface to avoid a sharp reflective surface.
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Acoustic coupling material is a material that passes ultrasonic waves, usually
from a probe to a subject or tissue to be interrogated. It is usually not a
living material
and is most often a polymer or gel or acoustic coupler.
Acoustic mirror refers to a device that can reflect an ultrasonic wave and
redirect
the ultrasonic wave in a predetermined manner. If the original ultrasonic
waves are
transmitted at an angle a, which is measured relative to the surface of the
plane of the
acoustic minor, the reflected ultrasonic waves can be oriented at an angle a'
= 180 - a
relative to the plane of the acoustic mirror. An acoustic mirrors) can be used
in an
ultrasonic system to vary the transmission angle.
Anatomical region refers to a site on the surface of the skin, tumor, organ or
other definable biomass that can be identified by an anatomical features) or
location.
Anatomical region can include the biomass underlying the surface. Usually,
such a
region will be definable according to standard medical reference methodology,
such as
that found in Williams et al., Gray's Anatomy, 1980.
BUA means broadband ultrasonic attenuation and when measured a BUA value
is expressed as dB/MHz. Note that actual attenuation of broadband ultrasonic
waves
increases as soft tissue thickness increases, while BUA values (dB/MbIz)
decrease as
soft tissue thickness increases. This distinction is often not recognized in
the literature,
which leads to misleading or potentially misleading conclusions about the
effect of soft
tissue on actual attenuation of broadband ultrasonic waves and BUA values.
A - scan refers to an ultrasonic technique where an ultrasonic source
transmits an
ultrasonic wave into an object, such as a patient's body, and the amplitude of
the
returning echoes (signals) are recorded as a function of time. Structures thaf
lie along
the direction of propagation are interrogated. As echoes return from
interfaces within
the object or tissue, the transducer crystal produces a voltage that is
proportional to the
echo intensity. The sequence of signal acquisition and processing of A - scan
data in a
modern ultrasonic instrument usually occurs in six major steps:
Detection of the echo (signal) occurs via mechanical deformation of the
piezoelectric crystal and is converted to an electric signal having a small
voltage.
Preamplification of the electronic signal from the crystal, into a more
useful range of voltages is usually necessary to ensure appropriate signal
processing.
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Time Gain Compensation compensates for the attenuation of the
ultrasonic signal with time, which arises from travel distance. Time gain
compensation may be user-adjustable and may be changed to meet the needs of
the specific application. Usually, the ideal time gain compensation curve
corrects the signal for the depth of the reflective boundary. Time gain
compensation works by increasing the amplification factor of the signal as a
function of time after the ultrasonic pulse has been emitted. Thus, reflective
boundaries having equal abilities to reflect ultrasonic waves will have equal
ultrasonic signals, regardless of the depth of the boundary.
Compression of the time compensated signal can be accomplished using
logarithmic amplification to reduce the large dynamic range (range of smallest
to largest signals) of the echo amplitudes. Small signals are made larger and
large signals are made smaller. This step provides a convenient scale for
display
of the amplitude variations on the limited gray scale range of a monitor.
1 S Rectification, demodulation and envelope detection of the high frequency
electronic signal permits the sampling and digitization of the echo amplitude
free of variations induced by the sinusoidal nature of the waveform.
Rejection level adjustment sets the threshold of signal amplitudes that are
permitted to enter a data storage, processing or display system. Rejection of
lower signal amplitudes reduces noise levels from scattered ultrasonic
signals.
B - scan refers to an ultrasonic technique where the amplitude of the detected
returning echo is recorded as a function of the transmission time, the
relative location of
- - - -- the detector in the probe and the signal amplitude. This is often
represented by the
brightness of a visual element, such as a pixel, in a two-dimensional image.
The
position of the pixel along the y-axis represents the depth, i.e. half the
time for the echo
to return to the transducer (for one half of the distance traveled). The
position along the
x-axis represents the location of the returning echoes relative to the long
axis of the
transducer, i.e. the location of the pixel either in a superoinferior or
mediolateral
direction or a combination of both. The display of multiple adjacent scan
lines creates a
composite two-dimensional image that portrays the general contour of internal
organs.
Chip refers to any current and future electronic hardware device that can be
used
in a computational unit and can be used as an aid in controlling the
components of an
ultrasonic unit including: 1 ) timing and synchronizing trigger pulses and
subsequent
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transmission of ultrasonic waves, 2) measuring and analyzing incoming
ultrasonic
signals, 3) comparing data to predetermined standards and data cut-offs (e.g.
electronic
filtering), and 4) perfonming multiple other simple and complex calculations.
Typically,
a chip is silicon-based, micro-electronic circuit.
5 Computational unit refers to any current or future hardware, software (e.g.
computer program), chip or other device used for calculations or for providing
instructions now developed or developed in the future or combination thereof.
The
computational unit may be used for controlling the ultrasonic generator or
source, for
defining or varying the firing rate and pulse repetition rate (as well as
other parameters
10 related to the ultrasonic generator or source), for measuring a reflected
signal, for image
reconstruction in B-scan mode and for filtering and thresholding of the
ultrasonic signal.
Other applications of the computational unit to the methods and devices
described
herein will be recognized by those skilled in the art. The computational unit
may be
used for any other application related to this technology that may be
facilitated with use
15 of computer software or hardware. The computational unit may comprise a
computer
program product with instructions to control the ultrasonic system. Such
computer
program products may be stored in storage devices, such as hard drives, floppy
discs,
electronic storage devices or any other storage device capable of reliable
storage and
retrieval of information (including electronic signals).
20 Crystal refers to the material used in the ultrasonic transducer to
transmit
ultrasonic waves and includes any current and future material used for this
purpose.
Crystals typically consist of lead zirconate titanate, barium lead titanate,
lead
metaniobate; lithium sulfate and polyvinylidene fluoride or a combination
thereof. A -
crystal is typically a piezoelectric material, but any material that will
contract and
expand when an external voltage is applied can be used, if such a material can
generate
ultrasonic waves described herein and known in the art. Crystals emit
ultrasonic waves
because the rapid mechanical contraction and expansion of the material moves
the
medium to generate ultrasonic waves. Conversely, when incoming ultrasonic
waves
deform the crystal, a current is induced in the material. The material then
emits an
electrical discharge that can be measured and, ultimately, with B-scan
technology, can
be used to reconstruct an image. Crystals or combinations of crystals with
dipoles that
approximate the acoustic impedance of human tissue are preferred, so as to
reduce the
impedance mismatch at the tissue/probe interface.
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Detector refers to any structure capable of measuring an ultrasonic wave or
pulse, currently known or developed in the future. Crystals containing dipoles
are
typically used to measure ultrasonic waves. Crystals, such as piezoelectric
crystals,
shift in dipole orientation in response to an applied electric current. If the
applied
electric current fluctuates, the crystals vibrate to cause an ultrasonic wave
in a medium.
Conversely, crystals vibrate in response to an ultrasonic wave that
mechanically
deforms the crystals, which changes dipole alignment within the crystal. This,
in turn,
changes the charge distribution to generate an electric current across a
crystal's surface.
Electrodes connected to electronic circuitry sense a potential difference
across the
crystal in relation to the incident mechanical pressure. A transducer can be a
detector.
Echogenicity refers to the brightness of a tissue in an ultrasonic image
relative to
the adjacent tissues, typically on a B-scan image. Echogenicity is dependent
on the
amount of ultrasonic waves reflected by the tissue. Certain tissues are more
echogenic
than other tissues. Fatty tissue, for example, is more echogenic than muscle
tissue. For
identical imaging parameters, fatty tissue will thus appear brighter than
muscle tissue.
Consequently, image brightness can be used to identify different tissues.
Edema refers to a pathologic accumulation of fluid within or between body
tissues. Edema fluid can accumulate in the interstitial space (e.g., in an
extracellular
location) between tissue cells thereby expanding the interstitial space. Edema
fluid can
also accumulate within the cells.
Frame time, when used in the context of positioning an ultrasonic source,
refers
to the time that is required to move an ultrasonic source from a first to a
second position
(or other additional positions) and back using a mechanical motor or-other
current and
future devices. Frame time typically ranges from 10 ms to 2,000 ms.
Linear array refers to a transducer design where the crystals are arranged in
a
linear fashion along one or more axes. Crystals can be fired in sequential, as
well as
non-sequential and simultaneous firing patterns or a combination thereof. With
sequential firing, each crystal can produce an ultrasonic beam and receive a
returning
echo for data collection. The number of crystals in one array usually
determines the
number of lines of sight for each recording. With segmental firing, a group or
segment
of crystals can be activated simultaneously resulting in a deeper near field
and a less
divergent far field compared with sequential activation. A segmental linear
array
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produces, however, a smaller number of lines of sight when compared to a
sequential
linear array with the same number of crystals.
Mechanically connected refers to a connection between two or more mechanical
components, such as an ultrasonic source having at least two transmission
positions. A
mechanical connection between two transmission positions may be accomplished
using
a mechanical motor to rotate or move an ultrasonic source. Optionally, the
ultrasonic
source can be rotated or moved on a track to vary the transmission angle.
Mechanical motor refers to any device that can move a device, such as the
ultrasonic source, from at least a first to a second position and, if desired,
to additional
positions. A mechanical motor may employ a spring-like mechanism to move the
ultrasonic source from said first to said second position. A mechanical motor
may also
employ a hydraulic, a magnetic, an electromagnetic mechanism or any other
current and
future mechanism that is capable of moving the ultrasonic source from a first
to a
second position.
Programmed mechanical motor refers to any motor controlled by a program,
such as a program in a chip or computer. Such motors include mechanical,
electrical or
hydraulic devices to move an ultrasonic source from a first to a second
position, and if
desired to additional positions. The program usually defines the frame time
that the
mechanical motor moves the ultrasonic source from a first to a second position
and
back. If mare than two positions are used, the program can move the ultrasonic
source
to many different positions, as desired.
Oscillate refers to moving the ultrasonic source repetitively from a first to
a
second position or other additional positions and moving it back from the
second
position or other additional positions. Oscillating from the first to the
second position
and back may be achieved using a mechanical motor. Typically, transducers will
be
oscillated to vary the transmission angle.
Osteoporosis refers to a condition characterized by low bone mass and
microarchitectural deterioration of bone tissue, with a consequent increase of
bone
fragility and susceptibility to fracture. Osteoporosis presents most commonly
with
vertebral fractures due to the decrease in bone mineral density and
deterioration of
structural properties of the bone. The most severe complication is hip
fracture due to its
high morbidity and mortality.
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Plane refers to the surface of a cross-sectional area of tissue interrogated
by an
ultrasonic probe. In ultrasonic measurements, the portion of the tissue
included in the
measurement or image is more accurately referred to as a volume. The x-
dimension of
this volume reflects the length of the tissue plane, i.e. the length of imaged
tissue. The
x-dimension typically varies between 1 and 10 cm or more. The y-dimension of
this
volume reflects tissue depth from the plane, e.g. the distance from the skin
surface to a
reflection point in the tissue. Interrogation of the y-dimension (or depth of
the
interrogation) depends, among other things, on the type of transducer, the
type of tissue,
and the frequency with which the ultrasonic beam is transmitted. With higher
frequencies, tissue penetration decreases and the maximum depth from the
tissue plane
will decrease. The y-dimension typically varies between 1 and 30 cm. The z-
dimension
corresponds to the width of the plane that is interrogated. It typically
varies between 1
and 15-20 mm. It is understood that such dimensions are in reference to
ultrasonic
signals and interrogation. In addition, x, y, and z dimensions are also used
with
different meaning in the context of positioning probes, and devices for
locating probes
in different areas of an anatomical region.
Transmission angle refers to the angle of an ultrasonic beam that intersects
the
object or tissue plane. The transmission angle is normally measured with
respect to the
object or tissue plane. The object or tissue plane has a reference angle of
zero degrees.
For example, as the transmission angle increases toward 90 degrees relative to
the tissue
plane, the ultrasonic beam approaches an orthogonal position relative to the
tissue plane.
Preferably, ultrasonic measurements are performed when the ultrasonic beam is
orthogonal to the plane of the tissue. It is also preferable; in some
embodiments-of the
invention, to vary the transmission angle in a predetermined and controllable
manner in
order to interrogate anatomical region as a function of a preselected
transmission
angle(s). Varying the transmission angle is particularly useful for ultrasonic
methods
used for BUA and SOS measurements. Transmission angle can be varied by
changing
the position of a transducer with respect to the object to be interrogated.
First position refers to a position of an ultrasonic source (or transducer)
that
detects or transmits an ultrasonic signal or pulse, respectively. When
ultrasonic waves
are reflected from different tissue interfaces, reflective distances can be
measured to the
first position. Typically, the first position will have a predetermined
transmission angle
associated with it (e.g. 90, 80, 70 or 60 degrees). Reflective distances, can
be measured
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from the first position, and include, but are not limited to, the distance
between the
ultrasonic source and 1) a skin/soft tissue, 2) a skin/bone or 3) a soft
tissue/bone
interface. BUA and SOS can also be measured at the first position and if
desired
compared with measurements from other positions, particularly positions that
vary the
transmission angle.
Second position refers to a position of an ultrasonic source (or transducer)
that
transmits or detects an ultrasonic pulse or signal, respectively and having
either a
different transmission angle from the first position or a different anatomical
location
than the first position. It is understood that the second position may have
the same
anatomical location as the first position while having a different
transmission angle
compared to the first position. When the ultrasonic waves are reflected at the
different
tissue interfaces, reflective distances can be measured to the second
position. Typically,
the first position will have a predetermined transmission angle associated
with it (e.g.
90, 80, 70 or 60 degrees). Reflective distances, can be measured from the
second
position, and include, but are not limited to, the distance between the
ultrasonic source
and 1) a skin/soft tissue, 2) a skin/bone or 3) a soft tissue/bone interface.
BUA and SOS
can also be measured at the second position and if desired compared with
measurements
from other positions. In some applications it will be desirable for the first
and second
positions to generally have the same anatomical location while varying the
transmission
angle. Additional positions can be readily achieved by relocating the
ultrasonic source
to either vary the anatomical location of interrogation or the transmission
angle.
Transmission freguency refers to the frequency of the ultrasonic wave that is
being transmitted from the ultrasonic source. Transmission frequency typically
ranges-- - - -
between 0.2MHz and 25MHz. Higher frequencies usually provide higher spatial
resolution. Tissue penetration decreases with higher frequencies. Lower
transmission
frequencies are generally characterized by lower spatial resolution with
improved tissue
penetration. Frequencies for BUA measurements typically range from 0.2MHz to
2MHz.
Ultrasonic pulse refers to any ultrasonic wave transmitted by an ultrasonic
source. Typically, the pulse will have a predetermined amplitude, frequency,
and wave
shape. Ultrasonic pulses may range in frequency between 20kHz and 20Mhz or
higher.
Ultrasonic pulses may consist of sine waves with single frequency or varying
frequencies, as well as single amplitudes and varying amplitudes. In addition
to sine
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waves, square waves or any other wave pattern may be employed. Square waves
may
be obtained by adding single-frequency sine waves to other sine waves. The
summation
of waves can then result in a square wave pattern.
Ultrasonic signal refers to any ultrasonic wave measured by an ultrasonic
5 detector after it has been reflected from the interface of an object or
tissue. Ultrasonic
signals may range in frequency between 20kHz and 20Mhz or higher.
Ultrasonic source refers to any structure capable of generating an ultrasonic
wave or pulse, currently known or developed in the future. Crystals containing
dipoles
are typically used to generate an ultrasonic wave above 20 khz. Crystals, such
as
10 piezoelectric crystals, that vibrate in response to an electric current
applied to the crystal
can be used as an ultrasonic source. In some ultrasonic generators, multiple
ultrasonic
sources may be arranged in a linear fashion. This arrangement of ultrasonic
sources is
also referred to as a linear array. With linear arrays, ultrasonic sources are
typically
fired sequentially, although simultaneous firing of groups of adjacent
ultrasonic sources
15 or other firing patterns of individual or groups of ultrasonic sources with
various time
delays can be achieved as described herein or developed in the art. The time
delay
between individual or group firings can be used to vary the depth of the beam
in an
object.
Ultrasonic wave refers to either an ultrasonic signal or pulse.
2.0 INTRODUCTION
The present invention recognizes for the first time that errors arising from
misplacement of interrogation sites and overlying soft tissues in ultrasonic -
.
measurements (e.g. speed of sound and broadband ultrasonic attenuation) of
trabecular
and cortical bone can be corrected by positoning the transducers) with respect
to an
anatomical landmark and/or measuring the thickness of the soft tissues that
are
interposed in the scan beam. Previously, it was not recognized that ultrasonic
measurements could be improved by compensating for positioning or that soft
tissue
thickness can be used to correct measured values (e.g. SOS and BUA) for errors
introduced by overlying soft tissues, growth of regions (e.g. the ankle), or
interindividual size differences. Nor was it recognized that changes in ankle
shape or
position aresoft tissue thickness is a potential source of decreased accuracy
and
reproducibility of SOS and BUA measurements in patients with peripheral edema
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undergoing diuretic or other types of medical treatment of edema with
resultant
fluctuations in soft tissue thickness. The present invention includes
measuring soft
tissue thickness using A-scan or B-scan technology in various anatomical
locations used
for measuring SOS and BUA. The present invention also includes applying
appropriate
S corrections to SOS and BUA based on ultrasonic measurements of soft tissue
thickness,
mass, volume or other indicator of soft tissue known or developed in the art.
In addition, interrogation artifacts in SOS and BUA measurements are
particularly pronounced in patients with abnormally increased soft tissue
thickness that
is commonly encountered in patients suffering from peripheral edema due to
cardiovascular, renal, or hepatic disorders. Previous work failed to recognize
that soft
tissue swelling or fluctuations in soft tissue thickness in patients with
peripheral edema
can affect ultrasonic probe position relative to the underlying bone or other
underlying
structures to be measured. The inventors were the first to recognize that
changes in
ultrasonic probe position relative to the underlying bone induced by local or
generalized
soft tissue swelling or fluctuations in soft tissue thickness can reduce short-
term and
long-term in vivo precision of SOS and BUA measurements. The inventors were
also
the first to recognize that soft tissue swelling induced changes in ultrasonic
probe
position relative to the underlying bone can be particularly significant in
patients with
edema undergoing diuretic or other types of medical treatment of edema with
resultant
fluctuations in soft tissue thickness.
It was also not previously recognized that changes in soft tissue thickness or
local heterogeneity in soft tissue thickness may affect ultrasonic probe
position relative
to the tissue/structure to be measured in any medical and non-medical
ultrasonic
applications. The present invention overcomes these limitations by providing
devices
and methods to correct for changes in tissue structure. The invention also
includes
methods and devices based on the identification of anatomic landmarks of the
structure
to be measured or ultrasonic identification of anatomical landmarks adjacent
to the
structure to be measured with subsequent positioning of the ultrasonic probes
relative to
these anatomic landmarks. The present invention includes also positioning of
ultrasonic
probes using landmarks based on either 1) textural information (e.g. density,
SOS, BUA
or reflective distance or a combination thereof), or 2) 2 or 3 dimensional
contour
information 3) a combination thereof of the tissue or structure to be measured
and of
tissues or structures adjacent to the measurement site. The invention also
includes
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27
methods and devices that are not necessarily based solely on anatomical
landmarks, but
in some applications can be combined with anatomical landmark embodiments.
Preferably, many of the embodiments described herein are designed for
automated use
with a minimum of operator intervention and preferably with remote or computer
control of such devices.
Without limiting aspects of the invention to a particular mechanism of action,
the inventors believe that the poor correlations between quantitative
ultrasonic
techniques and other methods for assessing bone mineral density are often
caused by
variations in the position of the interrogated bone with respect to the
ultrasonic
transducers. Sources of such interrogation artifacts include variations in the
thickness
of the posterior or inferior heel pads that can, in turn, change the position
of the
calcaneus relative to the ultrasonic transducers. The angle of the tissue with
respect to
the ultrasonic transducer can also vary even if the transducer is reproducibly
located at
an interrogation site, which is another potential source of inaccuracy for BUA
and SOS
measurements. In all cases, differences in the amount of soft tissue
interposed in the
ultrasonic beam path can ultimately change the speed of sound and broadband
ultrasonic
attenuation.
Without limiting aspects of the invention to a particular mechanism of action,
the inventors also believe that the poor correlations between quantitative
ultrasonic
techniques and other methods for assessing bone mineral density are often
caused by
variations in the soft tissue overlying the interrogated bone of the ankle.
Sources of
such interrogation artifacts include variations in the thickness of the
interstitial layers,
muscle layers, and edema layers, and changes in the water content-of the ankle
that can,
in turn, change the basic ultrasonic properties of the ankle relative to the
absence or
alteration of such biological conditions. In all cases, differences in the
amount of soft
tissue (or other mass of lighter density than dense bone) interposed in the
ultrasonic
beam path can ultimately change the speed of sound and broadband ultrasonic
attenuation. The inventors were the first to recognize that changes in soft
tissue induced
by local or generalized soft tissue swelling or fluctuations in soft tissue
thickness can
reduce short-term and long-term in vivo precision of SOS and BUA measurements,
as
well as other ultrasonic measurements.
The present invention also recognizes for the first time that errors arising
from
heterogenous tissue structure in ultrasonic measurements of speed of sound and
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28
broadband ultrasonic attenuation of trabecular and cortical bone can be
reduced or
corrected by measuring ultrasonic properties of a tissue (e.g. amplitude
response as a
function of frequency, BUA or SOS) at different transmission angles.
Previously, it was
not recognized that ultrasonic measurements at predetermined transmission
angles can
be used to correct measured SOS and BUA values for errors introduced by
overlying
soft tissues. Nor was it recognized that tissue heterogeneity is a potential
source of
decreased accuracy and reproducibility of SOS and BUA measurements in patients
with
peripheral edema undergoing diuretic or other types of medical treatment of
edema with
resultant fluctuations in tissue heterogeneity. The present invention includes
measuring
ultrasonic properties of tissues (e.g. BUA and SOS) using various transmission
angles to
reduce artifacts imposed by variations in tissue structure that can affect
such
measurements. The present invention also includes applying appropriate
corrections to
SOS and BUA based on ultrasonic measurements at predetermined, multiple
transmission angles.
Without limiting aspects of the invention to a particular mechanism of action,
the inventors also believe that the poor correlations between quantitative
ultrasonic
techniques and other methods for assessing bone mineral density are often
caused by
structural variations in the interrogated tissue (including the interrogated
bone) with
respect to the position of the ultrasonic transducers. Sources of such
interrogation
artifacts include variations in the thickness of the posterior or inferior
heel pads,
variations in water content, variations in extracellular matrix density or
content (e.g.
protein), variations in soft-tissue organization, variations in cortical bone
density or
structure; and variations in trabecular-bone density or structure. Such
variations in .- - _. -
tissue structure can affect transmission of ultrasonic waves or pulses from
the
transmitter to the detector in other tissues as well. Ultrasonic measurements
of the
tissue can also vary even if the transducer is reproducibly located at an
interrogation site
because ultrasonic transmission through the tissue's structure may change as a
function
of position or transmission angle. In all cases, differences in the tissue
structures
interposed in the ultrasonic beam path can ultimately change the speed of
sound and
broadband ultrasonic attenuation as well as other ultrasonic properties.
In addition, interrogation artifacts in SOS and BUA measurements are
particularly pronounced in patients with abnormally increased soft tissue
thickness that
is commonly encountered in patients suffering from peripheral edema due to
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29
cardiovascular, renal, or hepatic disorders. Previous work failed to recognize
that soft
tissue swelling or fluctuations in soft tissue thickness in patients with
peripheral edema
changes, not only the thickness, but the acoustic properties of the
interrogated tissue.
The inventors were the first to recognize that changes in ultrasonic
properties of
interrogated tissue induced by local or generalized soft tissue swelling or
fluctuations in
soft tissue physiology can reduce short-term and long-term in vivo precision
of SOS and
BUA measurements. The inventors were also the first to recognize that soft
tissue
swelling induced changes in ultrasonic properties of interrogated tissue
overlying bone
can be particularly significant in patients with edema undergoing diuretic or
other types
of medical treatment of edema with resultant fluctuations in soft tissue
physiology or
homeostasis.
FIG. 9A through FIG. 9D illustrate tissue structure variations that can lead
to
acoustic variations in ultrasonic measurements due to changes in the
interrogation path.
Three types of tissue structure variations are present in such figures: 1)
soft tissue
structure heterogeneity (as shown FIG. 9A through FIG. 9D), 2) dense tissue
heterogeneity (compare for example FIG. 9A with FIG. 9C) and 3) tissue
structure
variations due to changes in the physiology of the tissue (compare FIG. 9A
with FIG.
9C).
FIG. 9A and FIG. 9B show a tissue interrogated by an ultrasonic transducer
(940; T) that transmits to an ultrasonic receiver (950; R) (or detector) at
different
transmission angles and with different axes of transmission. The axis of
transmission is
shown as a (or (3) and has a transmission path from T to R. The transmission
path
passes through- the tissue comprising skin (900), soft tissue (represented as
white),
locations of organized biomaterial (910) with acoustic properties different
from that of
the extracellular fluid in the soft tissue (e.g. differences in echogenicity,
scatter, SOS,
BUA, or reflection), amorphous, insoluble biomaterial deposits (920) with
acoustic
properties different from that of the extracellular fluid in the soft tissue
(e.g. differences
in echogenicity, scatter, SOS, BUA, or reflection), and dense tissue (930)
with acoustic
properties different from that of the extracellular fluid in the soft tissue.
Comparison of
the transmission paths of FIG. 9A and FIG. 9B shows that the transmission path
traverses tissue structures with different acoustic properties. Hence, the
ultrasonic
measurements, such as the BUA or SOS, will not be the same depending on the
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transmission path, which can be changed by either varying the transmission
angle or the
axis of transmission in an anatomical region.
In addition, the transmission path from R to T traverses tissue structures
with
different acoustic properties in a spatial or time order that is different
from the
5 transmission path from T to R. Hence, the ultrasonic measurements, such as
the BUA
or SOS, will not be the same depending on the direction of the transmission
path, which
can be changed by either varying the direction of transmission in an
anatomical region
from T to R or from R to T.
FIG. 9C and FIG. 9D show the same tissue as FIG. 9A and FIG. 9B in a
10 different physiological state that changes the dimensions of the tissue and
its underlying
structure. The tissue is interrogated by an ultrasonic transducer (940; T)
that transmits
to an ultrasonic receiver (950; R) (or detector) at different transmission
angles and with
different axes of transmission as in FIG. 9C and FIG. 9D. The axis of
transmission is
shown as a (or (3) and has a transmission path from T to R. The transmission
path
15 passes through the tissue comprising skin (900), soft tissue (represented
as white),
locations of organized biomaterial (910) with acoustic properties different
from that of
the extracellular fluid in the soft tissue (e.g. differences in echogenicity,
scatter, SOS,
BUA, or reflection), amorphous, insoluble biomaterial deposits (920) with
acoustic
properties different from that of the extracellular fluid in the soft tissue
(e.g. differences
20 in echogenicity, scatter, SOS, BUA, or reflection}, and dense tissue (930)
with acoustic
properties different from that of the extracellular fluid in the soft tissue.
Comparison of
the transmission paths of FIG. 9A and FIG. 9C shows that the transmission path
- traverses tissue structures with different acoustic properties due to the
different - -- ---
physiological states in the tissue at different times. Hence, the ultrasonic
measurements,
25 such as the BUA or SOS, may not be the same depending on the physiological
state of
the interrogated tissue. Assessment of such differences in physiological
states can be
more accurately determined by either varying the transmission angle or the
axis of
transmission in an anatomical region. FIG. 9E shows received signals in such
tissue in
different physiological states and at different transmission angles.
30 By way of introduction, and not limitation of the various embodiments of
the
invention, the invention includes at least seven general aspects:
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1 ) an ultrasonic method of measuring thickness of soft tissues interposed in
the ultrasonic beam path in conjunction with measurements of speed of
sound and broadband ultrasonic attenuation;
2) a method of correcting measured speed of sound and broadband
ultrasonic attenuation for errors introduced by soft tissues interposed in
the beam path between the ultrasonic transducers and the object to be
measured;
3) an ultrasonic method that identifies anatomic landmarks of the structure
to be measured and subsequently positions the ultrasonic probes over the
measurement area using these anatomic landmarks;
4) an ultrasonic method that identifies anatomic landmarks adjacent to the
structure to be measured and subsequently positions the ultrasonic
probes) over the measurement area using these anatomic landmarks;
5) an ultrasonic method that identifies anatomic landmarks using different
transmission angles;
6) an ultrasonic method that measures ampliture as a function of enerty,
BUA or SOS or both using different transmission angles; and
7) devices and systems to achieve or facilitate the methods 1 through 6.
These aspects of the invention, as well as others described herein, can be
achieved using the methods and devices described herein. To gain a full
appreciation of
the scope of the invention, it will be further recognized that various aspects
of the
invention can be combined to make desirable embodiments of the invention. For
example, the aspects 1 and 2- of the invention can be combined with aspects 3
and/or 4
of the invention thereby improving reproducibility of measurements of SOS and
BUA
even further.
3.0 AUTOMATED SYSTEM FOR POSITIONING ULTRASONIC TRANSDUCERS AND
RELATED METHODS
Ultrasonic -~vst m and ,an~mnrlr notnrtinr~' ~ctvss~c
The present invention includes an ultrasonic system for ultrasonic
interrogation
of heel tissue for BUA or SOS. The system is based, in part, on improving BUA
or
SOS measurements by creating a anatomical landmark, anatomical maps ("maps")
or
both. In the preferred embodiments the ultrasonic system is adapted to provide
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32
anatomical landmarks and interrogate tissues for either broadband ultrasonic
attenuation
or speed of sound measurements.
The invention also includes an ultrasonic system for tissue BUA or SOS
measurements using anatomic landmarks that can be identified by the system.
Such a
system can include an ultrasonic transducer unit for BUA, SOS, or both
comprising a
pair of ultrasonic transducers where a first member of the pair is designed to
transmit
signals and a second member of the pair is designed to receive signals. A
computational
unit can be part of the system and is designed to manage ultrasonic signal
transmission
and reception of the ultrasonic transducer unit and to process signals to
identify an
anatomical landmark in an anatomical region, as well as BUA and SOS
measurements.
For instance, the computational unit is designed to process ultrasonic signals
received
from the ultrasonic transducer unit to generate an anatomical map of the
anatomical
region and identify the anatomic landmark within the anatomical region. The
map can
provide computer stored coordinates to locate the anatomic landmark within the
anatomical region or map for current or future aid in positioning the
transducer with x, y
positioners, as described herein or known in the art. Typically, anatomical
landmarks
are about 10 percent or less of the area of a map and preferably less than
about 2 to 0.2
cm. Preferably, the transducer units and computational unit have adapted A-
scan or B-
scan operation and more preferably can be used for measuring other ultrasonic
properties as described herein or have transducers adapted to measure such
other
properties. Preferably, the process of identifying an anatomical landmark is
programmed into the computational unit to permit highly automated
interrogation. Such
an anatomical landmark can either allow an operator to -locate a transducer or
allow a __.
computer to locate a transducer or some combination thereof.
In many embodiments of a landmark system it will be useful to compare
landmarks within an anatomical region for BUA or SOS measurement. The same
landmark may be compared at different times (intra-landmark comparison) or one
or
more landmarks may be compared (inter-landmark comparison). For instance, an
intra-
landmark comparison can be used during a single interrogation protocol that
entails
multiple interrogations of the same region with reference to a particular
anatomical
landmark. The computational unit can also further comprise a database
comprising
reference anatomical maps and the computational unit is further designed to
compare
the anatomical map with the reference anatomical map. The reference anatomical
map
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33
may be historic (from the same or another patient, generated as part of an
interrogation
protocol), or theoretical or any other type of desired reference map. The
reference map
can include a reference anatomical landmark, or if desired the landmark may be
stored
alone.
S
The present invention includes an ultrasonic system for ultrasonic
interrogation
of tissue. The system is based, in part, on improving ultrasonic measurements
by
creating a desired axis of transmission or spatial relationship between two
ultrasonic
transducers and their transmission paths (or reception paths). In the
preferred
embodiments, the ultrasonic system is adapted to interrogate dense tissues to
measure
either broadband ultrasonic attenuation or speed of sound.
Typically, such a system includes a first ultrasonic transducer with an axis
of
transmission in common with a second ultrasonic transducer. The axis of
transmission
is usually through a portion of a dense tissue and usually the transducers are
not
permanently fixed but are capable of being repositioned to a predetermined or
desired
location. The two transducers can be aligned (e.g. mechanically aligned) to
have a
common axis of transmission. In such situations, the transducers will be
generally
directed at each other to receive signals from each other. In some
applications, the
transducers may not have an axis of transmission in common but are instead
arranged to
each have a predetermined axis of transmission, wherein each transducer may
send
signals that can be received by the other transducer without having a common
axis of
transmission. The axis of transmission for each transducer will have an angle
of
transmission associated with it. Preferably, the transducers are adapted for A
scan or B
scan mode. Alternatively, tandem transducers can be used wherein each tandem
transducer is comprised of 1 ) a transducer designed for A scan or B scan, and
2) a
transducer designed for either broadband ultrasonic attenuation or speed of
sound
measurements or both. It is understood that a tandem transducer can be paired
so that,
for instance, the broadband ultrasonic transducer in the first tandem
transducer transmits
signals and the broadband ultrasonic transducer in the second tandem
transducer
receives signals.
In some embodiments the axis of transmission of each transducer is
predetermined or selected in advance of, or during, transmission or reception
of,
ultrasonic waves. The axis of each transducer can be adjusted or directed to
permit
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34
either 1) a partial overlap (typically less than about a twenty percent
overlap in the
acoustic field), 2) a substantial overlap (typically more than about a twenty
percent
overlap in the acoustic field), 3) a complete overlap (typically more than
about a ninety
percent overlap in the acoustic field) or 4} no overlap (typically less than
about a five
S percent overlap in the acoustic field) with an axis of transmission of
another transducer.
Partial overlap of each axis of transmission facilitates interrogation of
tissue
from two separate interrogation sites while pemitting 1) interrogation of
tissue by a
single transducer (where there is no substantial overlap of each axis of
transmission) or
2) interrogation of tissue by two or more transducers (where there is a
partial overlap of
each axis of transmission). Typically, the sites of interrogation are at least
about 1 cm
apart, often at least about 4 cm apart and sometimes about 6 cm or more cm
apart.
Transducers at interrogation sites can also be positioned on different faces
or sides of a
tissue to be interrogated (e.g. on the medial and lateral portion of an
appendage). In
many of these embodiments the transducers receive signals from each other.
Preferably,
1 S tandem transducers are used that are adapted or programmed to receive
signals from
each other.
The invention, however, is not limited to such embodiments and a plurality of
predetermined axes of transmission for plurality of transducers can be
established,
wherein the transducers are either adapted not receive signals from other
transducers in
the system or the signals received and transmitted by each transducer are
separately
processed. Similarly, substantial or complete overlaps can be achieved if so
desired in
some embodiments.
Multiple transducers can also be used to create multiple overlaps between each-
axis of transmission. Each axis of transmission can overlap the same area in a
tissue to
2S permit interrogation of the tissue by multiple transducers from separate
interrogation
sites. For example, multiple transducers can be directed to have overlapping
axes of
transmission to form a desired interrogation volume or path in the tissue
(e.g. an
interrogation volume substantially shaped like a column or cone). Multiple
transducers
creating common interrogation volumes from separate interrogation sites using
overlapping axes of transmission can improve resolution of internal structures
or
surfaces.
Without limiting aspects of the invention to a particular mechanism of action,
common interrogation volumes can give rise to enhanced, or more precise,
ultrasonic
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measurements due to any one or combination of the following factors. One,
reduction
in interference and scatter by comparing ultrasonic properties (e.g.
ultrasonic data in the
form of A scan or B scan) from each transducer and selecting the data with the
least
amount of interference to use in a reconstruction, map or ultrasonic analysis
of the
5 tissue. Two, reduction in ultrasonic wave attenuation (not necessarily
broadband
ultrasonic attenuation) by comparing ultrasonic properties (e.g. ultrasonic
data in the
form of A scan or B scan) from each transducer and selecting the data with the
least
amount of attenuation to use in a reconstruction, map or ultrasonic analysis
of the tissue.
Three, signal averaging between each transducer participating in constructing
the
10 interrogation volume. Such signal averaging would typically account for the
different
interrogation sites location of each transducer, the amount of axis of
transmission
overlap or selection of the most accurate data generated for each transducer
or a
combination thereof. Four, predetermined noise amplitude cancellation by
transmitting
ultrasonic waves from a first transducer to cancel ultrasonic waves generated
from a
15 second transducer that are creating ultrasonic waves or disturbances that
causes the
noise. Five, unreceived, anticipated signal analysis, which entails analyzing
the absence
of, or change in, signals that are anticipated or predicted to be received by
a detector.
The absence or change in signals will be indicative of the presence of
structures in the
path that remove or alter the transmitted ultrasonic signal.
20 Interference, scattering and attenuation, as well as other sources of
error, may
vary between transducers because the transducers are located at separate
interrogation
sites offering different interrogation paths with varying levels of
interference, scattering,
attenuation; etc. This is based, in part, on the property of ultrasonic
hysteresis meaning
either 1) the path of an ultrasonic signal transmitted by a transducer through
an object of
25 varying compositions with a heterogenous organization returns to the
transducer by a
different path and with an altered wave form or 2) the path of an ultrasonic
signal
transmitted by a first transducer through an object of varying compositions
with a
heterogenous organization will be received by a second transducer by a
different path
and with an altered wave form compared to an ultrasonic signal transmitted by
the
30 second transducer through the same object and received by the first
transducer.
For example, a model interrogation site has layers, from the first side of the
object to the second side of the object, of A, B, and C. Wherein layer A, B
and C all
have different speed of sound constants, and different microstructures
contributing to
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36
interference, attenuation and scatter. A signal moving from A to C and back
again will
have traveled a different path than a signal moving from C to A and back
again. A
transducer that transmits and receives signals at an interrogation site on the
surface of
layer A will receive a different set of signals compared to a transducer that
transmits
and receives signals at an interrogation site on the surface of layer C.
Alternatively, a
signal moving from A to C will have traveled a different path than a signal
moving from
C to A. A transducer that receives signals at an interrogation site on the
surface of layer
C from a transducer sending signals from layer A will receive a different set
of signals
compared to a transducer that receives signals at an interrogation site on the
surface of
layer A from a transducer located on the surface of layer C. Consequently, the
received
signals will have different properties dependent on the path taken through the
object.
The different interrogation paths of each transducer offers the ability to
sample
the data from each path and select the best or appropriate data using defined
selection
criteria, thereby reducing the source of error or enhancing interrogation of
the tissue.
For example, in an interrogation of a tibial region a transducer placed on the
anterior
surface of the tissue may have a sharp and intense reflective surface 1 cm
below the
surface of the skin indicating bone. The same interrogation site will have
little ability to
interrogate the muscle "behind" the bone. A second transducer positioned at a
second
interrogation site on the posterior region of the same tibial region will
offer relatively
greater ability to interrogate the muscle "behind" the bone compared to the
first
interrogation site since the muscle is now interrogated using ultrasonic waves
that have
not been deflected off or attenuated by bone. Data analysis that selects and
combines
data from each interrogation, and optionally including signal averaging, can
be used to- - - - .
generate a reconstruction, map, or ultrasonic analysis of the tissue. Such
positioning
methods and devices can be used with BUA or SOS, as well as imaging
techniques.
Methods and devices used to generate a common interrogation volume, as well
as other methods and devices herein, can aid in producing anatomic maps of the
tissue
or imaging of the tissue. It can also be used in conjunction with invasive
procedures as
guide or monitor of the progress of the procedure, such as catheterization,
trocar based
procedures or other types of surgery.
Some examples of different embodiments of tandem transducers related to an
axis of transmission are as follows:
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37
1 ) a common axis of transmission with each transducer substantially
orthogonal
to the tissue plane,
2) a common axis of transmission with each transducer not substantially
orthogonal to the tissue plane (e.g. a first transducer has a transmission
angle
S 75 degrees and a second transducer has a transmission angle of 105 degrees),
3) a predetermined axis of transmission for a first transducer and a second
transducer, wherein there is a partial overlap of each predetermined axis of
transmission of the first and second transducer and each transducer is
substantially orthogonal to the tissue plane, and
4) a predetermined axis of transmission for a first transducer and a second
transducer, wherein there is a partial overlap of each predetermined axis of
transmission of the first and second transducer and each transducer is not
substantially orthogonal to the tissue plane.
Some examples of different embodiments of plurality of transducers (e.g., 2,
3,
4, 5, 6 or more) related to a desired interrogation volume are as follows:
5) a desired interrogation volume generated from a common axis of
transmission with each transducer substantially orthogonal to the tissue
plane,
6) a desired interrogation volume generated from a plurality of transducers
each
having an axis of transmission at a predetermined angle with respect to the
other transducers or the tissue plane (e.g. a first transducer has a
predetermined angle of 60 degrees with respect to a second transducer and a
predetermined angle of 120 degrees with respect to a third transducer); and
7) a desired interrogation volume generated from a predetermined axis of
transmission for a first transducer and a second transducer, wherein there is
a
partial overlap of each predetermined axis of transmission of the first and
second transducer and each transducer is substantially orthogonal to the
tissue plane.
Generally, the system will include an x, y positioner that engages the first
ultrasonic transducer and the second ultrasonic transducer to locate each
transducer in
the appropriate position on the object to be interrogated. Usually, the x, y
positioner
positions the first ultrasonic transducer and the second ultrasonic transducer
while
generally maintaining the axis of transmission. The x, y positioner can be
designed to
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38
include positioning of each transducer independently or positioning of each
transducer
while simultaneously maintaining a common axis of transmission. The x, y
positioner
can position the ultrasonic transducer at a desired location along the x axis
and y axis of
the system. Typically, the x axis is the horizontal axis and the y axis is
vertical axis.
Preferably, a z-positioner will be included in the positioning unit to move a
transducer
to or away from an interrogation site.
A computational unit can be included in the system to manage ultrasonic
measurements. Typically, the computational unit is designed to manage
ultrasonic
signal transmission and reception of the first ultrasonic transducer and the
second
ultrasonic transducer. It may also be designed to optionally control movement
of the
positioning unit (e.g. x, y positioner). By monitoring signal transmission and
reception
the computational unit can instruct the x, y positioner to appropriately
locate the
transducers in order to achieve the desired relationship between the axis of
transmission
of each transducer. For example, FIG. 1 shows one method of instructing a
positioner
and interrogating a tissue based on anatomical maps. In many instances the
computational unit can be programmed to instruct the x, y positioner to
establish a
common axis of transmission between the two transducers. As described herein,
this is
a particularly useful embodiment for broadband ultrasonic attenuation and
speed of
sound measurements in the human heel.
It is also contemplated to use such a system in other anatomical regions where
ultrasonic measurements would benefit from controlled or predetermined x, y
positioning with two or more probes (e.g. imaging). Typically, the
computational unit
- is programmed to generate anatomical maps-using.either A scan or B scan data
or both. - .
Maps can also be generated using other ultrasound parameters, e.g. Doppler
information
or flow information acquired with ultrasonic contrast agents.
In greater detail, FIG. 1 shows one embodiment of the invention relating to
methods of interrogating a tissue, generating an anatomical map or instructing
a
positioner to position a transducer(s). An anatomical map is generated from
data
obtained by interrogating the tissue at a first transducers) positions) (n,).
This can be
done using any ultrasonic measurement, such as A scan or B scan or both. A
clinical
measurement is then made at the first position n,. Any clinical measurement
can be
used including, SOS, BUA, x-ray, or tomography, as well as a surgical
procedure. The
process of interrogation, map generation and clinical measurement can be
repeated at
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39
each subsequent position (n~, n2, ...). Optionally, the anatomical map can be
compared to
a reference map that is usually stored in the computational unit. When a
suitable match
occurs with the reference map, interrogation can be initiated. Such matches
can be
based on predetermined match criteria, including anyone or combination of the
following criteria: percentage of contour overlap, homology between ultrasonic
features
in a given map (such as the percentage of features in common), and the
proximity of a
set of coordinates in the anatomical map to a defined set of coordinates in
the reference
map. If no match occurs, the positioner repositions the transducer(s), another
interrogation occurs and another map is generated and compared to the
reference map.
This process can be repeated until the desired match is obtained or until it
is determined
that no suitable match is possible. Typically, the positioner moves the
transducer in
increments until the desired location or interrogation site has been reached
and the
tissue is interrogated for clinical measurement, such as speed of sound or
broadband
ultrasonic attenuation measurement. Such methods can be adapted as
instructions for
components of a monitoring system that form a computer program product.
A system (e.g. BUA or SOS measurements) that includes one, two, or more
ultrasonic transducers, a positioning unit (e.g. an x, y positioner), and a
computational
unit for signal management and transducer positioning offers a number of
advantages.
First, transducer positioning can be automatically established without
significant
operator intervention, as well as with operator direction to a desired
position. Second,
accuracy and reproducibility of transducer positioning can be improved by
appropriately
programming the computational unit. Finally, adjustments to transducer
positioning
during interrogation can be accomplished with minimized interruption of the
interrogation process.
In another embodiment the computational unit directs a positioning unit to
position the transducer unit with reference to the anatomical landmark prior
to BUA or
SOS measurement. Preferably, anatomical landmarks in the heel are less than
about 2
cm2, more preferably about less than 1 cm2, and most preferably less than
about 0.5
cm2, unless the anatomical landmarks are based on contours. The transducer can
be
positioned by an iterative process to find a preprogrammed landmark (e.g.
historic) or to
identify a landmark by preprogrammed criteria. Typically, the computational
unit is
designed to instruct the transducer unit to transmit and receive signals after
positioning
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the transducer unit with respect to the anatomical landmark. This process can
be
repeated and is outlined in FIG. 2.
In greater detail, FIG. 2 shows another embodiment of the invention relating
to
methods of interrogating a tissue for BUA or SOS, identifying an anatomical
landmark
5 and instructing a positioner to position a transducer(s). The transducers)
is (are)
positioned. An anatomical map is generated from data obtained by interrogating
the
tissue at a first transducers) positions) (n~). This can be done using any
ultrasonic
measurement, such as A-scan or B-scan or both. A comparison of the map to
landmark
criteria is then made to identify a landmark at the first position n~. The
process of
10 positioning, interrogation, map generation and comparison can be repeated
at each
subsequent position (n1, n2, ...). After a landmark has been identified, a BUA
or SOS
measurement can be initiated. Typically, a computational unit directs a
positioning unit
to position the transducer unit with reference to an anatomical landmark. The
transducer can be positioned by an iterative process to identify a landmark,
e.g. based
15 on preprogrammed landmark criteria. Typically, the computational unit is
designed to
instruct the transducer unit to transmit and receive signals after positioning
the
transducer unit with respect to the anatomical landmark. Such methods can be
adapted
as instructions for components of a monitoring system that form a computer
program
product.
20 The ultrasonic system can further comprise a positioning unit for changing
the
spatial relationship between the anatomic landmark in the heel and the
ultrasonic
transducer unit, thereby permitting interrogation for BUA or SOS with
reference to the
anatomic -landmark in the anatomical region by positioning the transducer unit
with
respect to the anatomical landmark. The computational unit can further
comprise a
25 display for showing the anatomical map.
The system may optionally include a z positioner that engages and/or positions
at least one or more ultrasonic transducers. Preferably, both transducers can
be
positioned in the z dimension by the z positioner. The z positioner changes
the distance
of transmission along the axis of transmission between the first ultrasonic
transducer
30 and the second ultrasonic transducer. Typically, it changes the distance
between the
transducer and the interrogation with minimal compression of the interrogated
tissue. A
pressure sensor can be included on the surface of the transducer or other
location to
moW for transducer pressure against the interrogated tissue. The pressure
sensor can be
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41
part of control unit to regulate the amount of transducer pressure at the
interrogation site
by adjusting the transducer location in the z dimension with the z positioner.
If desired,
an electronic feedback loop can be included to adjust the transducer position
in the z
dimension in response to changes in pressure, which could arise from patient
S movement, tissue swelling or other factors that contribute to changes in
transducer
pressure. The z positioner can position the ultrasonic transducer at a desired
location
along the z axis of the system. Typically, the z axis is the axis
perpendicular to the x
axis which is the horizontal axis, and the y axis is the vertical axis. The z
positioner
moves the transducers) along the z-axis further or closer to the surface of
the
anatomical location.
The system may optionally include, or be designed as a dedicated device, to
achieve speed of sound or broadband ultrasonic attenuation measurements or
both.
Typically, in such a system the computational unit can estimate speed of sound
or
broadband ultrasonic attenuation in an interrogated tissue. Preferably, the
computational unit can correct the speed of sound or broadband ultrasonic
attenuation
measurements for errors generated by soft tissue effects. The Examples offer a
number
of methods for such correction. To accomplish correction methods the system
may
optionally include a computational unit that comprises a database of
correction factors
for soft tissue thicknesses and either speed of sound or broadband ultrasonic
attenuation
measurements. The database may also be comprised of factors related to
empirical
measurements of soft tissue and broadband ultrasonic attenuation, including
historic
patient records for comparison.
The x, y positioner included in the system can be any positioner that can
accurately position a transducer and maintain the transducer position during
interrogation. The x, y positioner can be those known in the art of
positioning devices
or those developed in the future or disclosed herein. In selecting an x, y
positioner the
following features should considered and incorporated into the x, y positioner
design
depending on the application: 1 ) ease of movement of the positioner
preferably with
automated control, 2) integration of the positioner into a computer control
system, 3)
accuracy of positioning (preferably within about ~ Smm, more preferably about
~ lmm
and most preferably about ~ O.OSmm), 4) speed of achieving a new position
should
typically be less than 2 to 4 seconds, and S) ability of the x, y positioner
to either locate
one transducer or two transducers. It is understood that the x, y positioner
may be
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42
configured in many arrangements. For instance, the x, y positioner may be
designed as
one positioning system that moves each transducer concurrently or as two x, y
positioners that move each transducer independently yet in a coordinated
fashion with
respect to each transducer. The x, y positioner can be manually controlled,
operator
computer controlled, or automatically controlled with minimal or no operator
intervention or a combination thereof. Preferably, the system is capable of
all three
modes of operation. If a manual mode is incorporated into the device, the x, y
positioner typically includes a grip to manually direct the first and second
transducers
over a desired anatomic region. Positioners in the art may used as well, such
as those
provided by Newport (Irvine, California), including stages for rectilinear
motion. The
positioning unit can be operated and designed for manual, computer operator or
automatic operation. Positioning units can be those devices known in the art
or
described herein to accomplish such functions.
In one embodiment, the x, y positioner can comprise a frame to maintain the
axis
of transmission between the first and second ultrasonic transducers. In this
embodiment
the x, y positioner maintains a "fixed" axis of transmission. Typically, these
types of
positioners can be less expensive to operate and robust under a variety of
clinical
conditions because the axis of transmission is fixed, typically during
manufacture or in
an adjustment protocol. Thus, the x, y positioner is not required to locate
the transducer
with respect to one another since this is predetermined. Instead the x, y
positioner can
be primarily designed to locate the transducer in tandem with a fixed common
axis of
transmission in relation to the anatomic region of interrogation. Typically,
the frame
engages an x-track and the x track engages a y track, thereby an operator can
move the
first and second ultrasonic transducers manually in either an x or y dimension
or
combination thereof with respect to an anatomic region. It is understood,
however, that
such tracks could also be located on separate frames without a fixed common
axis of
transmission between the two transducers and that a common axis of
transmission could
be established. The x, y positioner can be designed to accommodate an
appendage.
Typically, the appendage is held in a predetermined position in the ultrasonic
system
relative to the x, y positioner. Preferably, the x, y positioner is
automatically controlled
by the computational unit. In one arrangement, the computational unit
instructs an x
servo-motor to drive the first ultrasonic transducer and second transducer in
the x
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43
dimension and a y servo-motor to drive the first ultrasonic transducer and
second
transducer in the y dimension.
A key and useful feature of some embodiments of the invention is an ultrasonic
system wherein the computational unit comprises a computational program to
identify
an anatomic landmark (e.g. in the heel in conjunction with BUA or SOS
measurements),
as described further herein. For example, the ultrasonic system can be
designed
wherein the computational unit is designed to instruct the x, y positioner to
position the
first ultrasonic transducer and the second ultrasonic transducer to
interrogate the
anatomic landmark. Usually, the x, y positioner generally maintains the axis
of
transmission between the first ultrasonic transducer and the second ultrasonic
transducer
and generally through the anatomic landmark.
The anatomical landmark that is selected is part of an anatomical region
appropriate for BUA or SOS measurements in the heel, such as locations of
dense bone.
Other anatomical regions can be selected from the group consisting of a knee
and tibia.
1 S The x, y positioner can be adapted to accommodate the anatomical site.
Preferably, at
least the first ultrasonic transducer and the second ultrasonic transducer are
adapted for
either speed of sound or broadband ultrasonic attenuation (or both)
measurements inheel
tissue comprising bone. In another embodiment the computational unit can
identify an
anatomic landmark in an interrogated tissue and direct the x, y positioner to
position
over the anatomic landmark, thereby the first ultrasonic transducer and second
ultrasonic transducer have an axis of transmission generally through the
anatomic
landmark.
As an example of the invention, the use of an x, y positioner either alone or
in
conjunction with an anatomic landmark can facilitate speed of sound or
broadband
ultrasonic attenuation measurements in the heel. In FIGS. 3A and B the effect
of soft
tissue swelling is illustrated in ultrasonic measurements. By including an x,
y positioner
in an ultrasonic system, the transducers can be positioned to generally
maintain an
interrogation site that takes into account tissue swelling (or possibly
growth). The x, y
positioning system can also be used to generate a common axis of transmission
for
ultrasonic measurements, such as speed of sound measurements or broadband
ultrasonic
attenuation. By including a landmark detection system, as described herein,
even more
reproducible and accurate measurements can be made.
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In one embodiment, the invention includes methods and devices for correcting
for soft tissue in assessment of bone structure or dense tissue, particularly
for
osteoporosis. An ultrasonic method for determining broadband ultrasonic
attenuation or
speed of sound measurements in dense tissues, comprising:
a) interrogating a tissue with an ultrasonic transducer unit adapted for
either 1 )
broadband ultrasonic attenuation or 2) speed of sound measurements or both,
b) interrogating the tissue with the ultrasonic transducer to determine soft
tissue
thickness in the anatomical region with the ultrasonic transducer unit, and
c) determining dense tissue broadband ultrasonic attenuation, dense tissue
speed of
sound or both by correcting for the soft tissue thickness,
wherein the determining step generates a dense tissue broadband ultrasonic
attenuation value, dense tissue speed of sound value or both that is more
indicative
of a broadband ultrasonic attenuation value, or speed of sound value in dense
tissue
than in the absence of correcting for soft tissue thickness.
The ultrasonic method can include a further refined determining step that
further
comprises adjusting either 1) broadband ultrasonic attenuation or 2) speed of
sound in
the tissue or both for the soft thickness based on a database of ultrasonic
measurements
from comparable tissues. The database measurements include soft tissue
thickness and
either a) broadband ultrasonic attenuation, b) speed of sound or c) both. The
determining step can comprise adjusting either 1) broadband ultrasonic
attenuation, 2)
speed of sound in the tissue or 3) both for the soft thickness based on a
correction factor.
These methods can be applied at the heel. Often such measurements can include
calculating speed of sound for calcaneus tissue using Equation 16 or other
equations or
methods described herein or described in the art.
In a related embodiment of the invention, soft tissue thickness measured in a
patient is compared to reference soft tissue thickness obtained from a control
population
(e.g. age-, sex-, race-, or weight-matched normal subjects). Reference soft
tissue
thickness can be generated by measuring soft tissue thickness in healthy
subjects with
normal vascular, cardiac, hepatic, or renal function and no other underlying
medical
condition. Reference soft tissue thicknesses can be expressed as but are not
limited to,
mean and standard deviation or standard error. Reference soft tissue
thicknesses can be
obtained independently for patients 15-20, 20-30, 30-40, 40-50, 50-60, 60-70,
70-80,
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and 80 and more years of age. Reference soft tissue thicknesses for these age
groups
can be obtained separately for men and women and for race (e.g. Asian,
African,
Caucasian, and Hispanic subjects). Additionally, reference soft tissue
thicknesses can
be obtained for different subject weights within each age, sex, and racial
subgroup.
5 Individual patients can be compared to a reference soft tissue thickness. If
patient's soft tissue thickness is elevated, a correction factor can be
applied. The
amount/magnitude of correction factor is influenced by the magnitude of
increase in soft
tissue thickness that can be influenced by the magnitude of fat, fibrous, and
muscle
tissue contribution. Clinical study groups can be evaluated to generate
databases for
10 further study or to generate more refined correction factors. Such study
groups include:
non-edematous non-osteoporotic premenopausal, non-edematous non-osteoporotic
postmenopausal, non-edematous osteoporotic postmenopausal; edematous non-
osteoporotic premenopausal, edematous non-osteoporotic postmenopausal, and
edematous osteoporotic postmenopausal patients. In each study group the
following
15 procedures can be performed for comparison: dual x-ray absorptiometry
("DXA") of the
spine, hip, or calcaneus, along with SOS and BUA measurements or quantitative
computed tomography ("QCT"). Evening measurements are preferred (the time of
maximum edema; and clinically frequent times for outpatient ambulatory office
visits).
Without limiting the invention to a particular mechanism of action, the
inventors
20 believe that correlation between DXA measurements and SOS and BUA will be
better
in non-edematous patients than in edematous patients (artificial change of SOS
and
BUA due to pathologic soft tissue thickening). Correction for soft tissue
thickness can
also improve- the accuracy and discriminatory power of SOS and BUA in non-
edematous and edematous patients. Even non-edematous patients will have
variations
25 in soft tissue thickness due to diet, obesity, sport related conditioning,
hormonal
influences, and the like. Such methods can also be used to identify population
with an
increased or decreased risk of bone fracture, particularly the fracture of the
hip, spine, or
long bones.
;loft Tissue Correction Devices
30 Current ultrasonic probes for measuring SOS and BUA are hand positioned
using visible or palpable regions on the skin surface (e.g. sole of the foot,
posterior
margin of the heel). In the calcaneus, pathologic soft tissue thickening, e.g.
from tissue
edema, will change the position of the calcaneus relative to the transducer on
the skin
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surface. Thus, the transducers) will measure over the same external area, but
will not
measure the same area in the calcaneus. This effect can be particularly
pronounced if
edema/soft tissue thickness changes between follow-up examinations (e.g.
baseline
examination in am with little or no edema, follow-up examination in pm with
more
pronounced edema). Thus, changes in probe position relative to the calcaneus
or other
bone will affect reproducibility of SOS and BUA as well as other US
measurements
significantly.
FIG. 4A shows an example demonstrating the influence of soft tissue thickness
on measurements of broadband ultrasonic attenuation. As the thickness of the
soft tissue
interposed in the scan path increases, measured broadband ultrasonic
attenuation values,
in this example of the calcaneus, decrease.
FIG. 4B shows an example demonstrating the results when measured broadband
ultrasonic attenuation is corrected for thickness of the soft tissue layers
interposed in the
scan path. This correction is typically performed by measuring soft tissue
thickness
with A-scan or B-scan ultrasonics. As the soft tissue thickness increases,
corrected
broadband ultrasonic attenuation values do not change significantly.
FIG. 5A shows an example of a typical prior art device for measuring the speed
of sound or broadband ultrasonic attenuation in a healthy non-edematous
patient. The
position of the patient's foot 500, of the calcaneus 510, and of the
ultrasonic
interrogation site 520 are fixed with respect to the device frame 530.
FIG. 5B shows an example of a typical prior art device for measuring the speed
of sound or broadband ultrasonic attenuation in a patient with peripheral
edema. Edema
increases the thickness of the soft tissue inferior and posterior to the
calcaneus. Since
the position of the ultrasonic interrogation site 520 is fixed relative to the
device frame
530, a more inferior and posterior region is measured within the calcaneus 510
when
compared to FIG. 5A that is even partially outside the calcaneus 510.
FIG. 5C shows one embodiment of the invention with a probe for measuring for
example speed of sound or broadband ultrasonic attenuation of the calcaneus,
in this
case in a healthy non-edematous patient. The position of the ultrasonic
interrogation
site 520 is not fixed with respect to the device frame 530 but is determined,
for example,
based on landmarks or anatomical maps using A-scan or B-scan ultrasonics.
FIG. 5D shows the same embodiment of the invention as seen in FIG. 5C with
a probe for measuring for example speed of sound or broadband ultrasonic
attenuation
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of the calcaneus, in this case in a patient with peripheral edema. Edema
increases the
thickness of the soft tissue inferior and posterior to the calcaneus. Since
the position of
the ultrasonic interrogation site 520 is not fixed relative to the device
frame 530, but is
determined, for example, based on landmarks or anatomical maps using A-scan or
B-
scan ultrasonics, the interrogation site in the calcaneus remains
substantially constant in
the presence of peripheral edema and does not change significantly compared to
conditions illustrated in FIG. 5C.
FIG. 6A shows another embodiment of the invention with a device for
measuring for example speed of sound or broadband ultrasonic attenuation of
the
calcaneus, in this case in a healthy non-edematous patient. The position of
the patient's
foot 600 and of the calcaneus 610 are not fixed with respect to the device
frame 650.
The ultrasonic transducer 620 is, however, attached 630 to the device frame
650. The
foot 600 is placed on a foot holder 640 that can be moved in the x- or y-
direction 660.
The foot 600 and the calcaneus 610 are positioned relative to the ultrasonic
transducer
620 for example based on landmarks or anatomic maps using A-scan or B-scan
ultrasonics.
FIG. 6B shows the same embodiment of the invention as demonstrated in FIG.
6A with a probe for measuring for example speed of sound or broadband
ultrasonic
attenuation of the calcaneus, in this case in a patient with peripheral edema.
Since the
position of the foot 600 and of the calcaneus 610 is not fixed relative to the
device
frame 650, but is determined, for example, based on landmarks or anatomical
maps
using A-scan or B-scan ultrasonics, the interrogation site of the ultrasonic
transducer
620 at the calcaneus remains substantially constant in the presence of
peripheral edema
and does not change significantly when compared to the condition illustrated
in FIG.
6A.
FIG. 7A shows another embodiment of the invention comprising two ultrasonic
transducers 700 attached to an x-positioner 710 and a y-positioner 720. The
heel 730
and the calcaneus 740 are seated on a foot holder 750. The ultrasonic
transducer 700 is
brought in contact with the heel 730 using a z-positioner member 760 that can
move in
and out of a frame 770 continuously or in a stepwise fashion. The ultrasonic
transmission axis 780 is also shown.
FIG. 7B is a side view of the ultrasonic transducer 700, the x-positioner 710,
and the y-positioner 720 shown in FIG. 7A showing the tracks of each
positioner.
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Typically, one positioner will engage the other positioner to permit x, y
movement
either concurrently (moving in both directions simultaneously) or sequentially
(moving
in one dimension first and then in a second dimension).
FIG. 7C shows another embodiment of the invention. The ultrasonic
transducers 700 are attached to a positioning system 790 that affords movement
of the
transducers in x, y, and z-direction, as well as angulation of the transducers
700 and the
resultant ultrasonic transmission axis 780. The angulation position of the
transducers
700 and the ultrasonic transmission axis 780 is substantially zero.
FIG. 7D shows the ultrasonic transducers 700 attached to a positioning system
790 that affords movement of the transducers in x, y, and z-direction, as well
as
angulation of the transducers 700 and the resultant ultrasonic transmission
axis 780.
The angulation position of the transducers 700 and the ultrasonic transmission
axis 780
is substantially different from zero.
FIG. 7E shows an expanded view of the embodiment presented in FIGS. 7A-D.
The ultrasonic transducer 700 is attached to a positioning system 790 that
affords
movement of the transducers in x, y, and z-direction, as well as angulation of
the
transducers 700. The ultrasonic beam 795 has substantially zero angulation.
FIG. 7F shows an expanded view of the positioning system 790 and the
ultrasonic transducers 700 with inferior angulation of the ultrasonic beam
795.
FIG. 7G shows an expanded view of the positioning system 790 and the
ultrasonic transducers 700 with superior angulation of the ultrasonic beam
795.
FIG. 8A is a front view of another embodiment of the invention where the
transducer 800-is moved along an x, y- positioner 810 using electromagnetic
forces
rather than using a mechanical or electro-mechanical x, y-positioner.
FIG. 8B shows a side view of the transducer 800 and the electromagnetic x, y-
positioner 810. The transducer 800 is brought in contact with the heel (not
shown) using
a z-positioner member 830 that is moved in and out of frame 840.
FIG. 8C shows a modification of the embodiment present in FIG. 8B. The
sides of the transducer 800 are isolated from the electromagnetic x, y-
positioner 810
using a flexible or movable electromagnetic insulator 840.
Many of the positioning embodiments of the invention can be used to assist in
enhancing such measurements and as described further herein anatomical
landmarks can
also be used to enhance measurements.
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For example, in one embodiment an A-scan or B-scan ultrasonic device is used
to identify a contour or landmarks of the calcaneus or other bone.
Specifically, the
posterior and inferior margin or other bony landmarks of the calcaneus (or
other bone)
are detected and registered spatially, e.g. on a coordinate system in the
system
computer. The transducers) for BUA and SOS measurements are subsequently
positioned using the bone margins or landmarks (inferior and posterior or
other) as
reference points or using the coordinate system. On follow-up examinations in
the same
patient, the system will automatically or using operator assistance find the
same bony
margins/landmarks and position the transducers) over the same measurement
sites) of
the calcaneus or other bone that was evaluated during the previous examination
(s).
This type of positioning ensures reproducible placement of the transducers)
over the
same measurement area of the calcaneus or other bone. In-vivo reproducibility
of any
type of SOS and BUA will be markedly improved using this technique. This
technique
is also applicable for improving reproducibility of measurements of soft
tissue or
internal organs, as described herein.
4.O ULTRASONIC SYSTEMS AND LANDMARK DETECTION SYSTEMS
The present invention includes an ultrasonic system for ultrasonic
interrogation
of tissue. The system is based, in part, on improving ultrasonic measurements
by
creating a anatomical landmark, anatomical maps ("maps") or both. In the
preferred
embodiments the ultrasonic system is adapted to provide maps and interrogate
tissues
for either broadband ultrasonic attenuation or speed of sound measurements.
The invention also includes an ultrasonic system for tissue ultrasonic
interrogation using anatomic landmarks that can be identified by the system.
Such a
system can include an ultrasonic transducer unit comprising either 1 ) a first
ultrasonic
transducer that can transmit and receive signals or 2) a pair of ultrasonic
transducers
where a first member of the pair is designed to transmit signals and a second
member of
the pair is designed to receive signals. A computational unit can be part of
the system
and is designed to manage ultrasonic signal transmission and reception of the
ultrasonic
transducer unit and to process signals to identify an anatomical landmark in
an
anatomical region. For instance, the computational unit is designed to process
ultrasonic
signals received from the ultrasonic transducer unit to generate an anatomical
map of
the anatomical region and identify the anatomic landmark within the anatomical
region.
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The map can provide computer stored coordinates to locate the anatomic
landmark
within the anatomical region for current or future aid in positioning the
transducer with
x, y positioners, as described herein or known in the art. Preferably, the
transducer units
and computational unit have adapted A scan or B scan operation and more
preferably
5 can be used for measuring other ultrasonic properties as described herein or
have
transducers adapted to measure such other properties. Preferably, the process
of
identifying an anatomical landmark is programmed into the computational unit
to
permit highly automated interrogation. Such an anatomical landmark can either
allow
an operator to locate a transducer or allow a computer to locate a transducer
or some
10 combination thereof.
In addition, echogenic markers can be introduced, either temporarily or
permanently, as anatomic landmarks in a predetermined position. Such landmarks
include: biocompatible metal probes, needles, stems, or other plastic, metal,
or gas
containing objects with a securing member to attach to the landmark in the
desired
15 position.
Typically, landmarks are based on least one ultrasonic property and preferably
two or three or more different properties. For instance, the landmark system
may be
part of a computational unit further designed to process received ultrasonic
signals from
the ultrasonic transducer unit to generate at least one data set of an
ultrasonic property
20 (e.g. A-scan) and to generate the anatomical map from at least some of the
data set. The
map itself can be an ultrasonic property correlated with the x, y position of
the x, y
positioner. It is understood that the data set may have more data than is
necessary to
- generate a particular map or a map may be produced..from a selection of data
from said __
data set. In one embodiment the ultrasonic property is selected from the group
25 consisting of broadband ultrasonic attenuation, echogenicity, reflective
surfaces,
distances from the transducer unit, speed of sound, ultrasonic images, Doppler
information and information obtained with ultrasound contrast agents.
Combinations of
these properties can generate particularly useful maps. For instance, an
anatomic
landmark may be identified by ultrasonic images in conjunction with echogenic
30 surfaces. Using multiple properties can help tailor the type of landmark
desired to be
identified. Landmark systems are particularly useful in areas where patient
morphology
may change but a particular anatomical feature may not, such as dense bone in
the heel.
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In many embodiments of a landmark system it will be useful to compare
landmarks within an anatomical region. The same landmark may be compared at
different times (intra-landmark comparison) or one or more landmarks may be
compared (inter-landmark comparison). For instance, an intra-landmark
comparison
can be used during a single interrogation protocol that entails multiple
interrogations of
the same region with reference to a particular anatomical landmark. The
computational
unit can also further comprise a database comprising reference anatomical maps
and the
computational unit is further designed to compare the anatomical map with the
reference anatomical map. The reference anatomical map may be historic (from
the
same or another patient, generated as part of an interrogation protocol), or
theoretical or
any other type of desired reference map.
Anatomical landmarks are extremely useful in positioning the transducer(s). In
an exemplary surgical protocol, landmarks can be identified in the tissue to
be examined
and during the endoscopic procedure surgical instruments can be manipulated
with
respect to such landmarks. Computer control of the transducers can maintain
visualization of the landmarks during the procedure. In addition, the
computational unit
can direct instruments or instruct physicians to direct the instruments in
relation to the
landmarks.
In another embodiment the computational unit directs a positioning unit to
position the transducer unit with reference to the anatomical landmark. The
transducer
can be positioned by an iterative process to find a preprogrammed landmark
(e.g.
historic) or to identify a landmark by preprogrammed criteria. Typically, the
computational unit is designed to instruct the transducer unit to transmit and
receive
signals after positioning the transducer unit with respect to the anatomical
landmark.
This process can be repeated and is outlined in FIG. 2.
In greater detail, FIG. 2 shows another embodiment of the invention relating
to
methods of interrogating a tissue, identifying an anatomical landmark or
instructing a
positioner to position a transducer(s). The transducers) is (are) positioned.
An
anatomical map is generated from data obtained by interrogating the tissue at
a first
transducers) positions) (n,). This can be done using any ultrasonic
measurement, such
as A scan or B scan or both. A comparison of the map to landmark criteria is
then
made to identify a landmark at the first position nl. The process of
positioning,
interrogation, map generation and comparison can be repeated at each
subsequent
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position (n~, n2, ...). After a landmark has been identified, a clinical
measurement or
surgical procedure can be initiated. Typically, a computational unit directs a
positioning
unit to position the transducer unit with reference to an anatomical landmark.
The
transducer can be positioned by an iterative process to identify a landmark,
e.g. based
on preprogrammed landmark criteria. Typically, the computational unit is
designed to
instruct the transducer unit to transmit and receive signals after positioning
the
transducer unit with respect to the anatomical landmark. Such methods can be
adapted
as instructions for components of a monitoring system that form a computer
program
product.
The ultrasonic system can further comprise a positioning unit for changing the
spatial relationship between the anatomic landmark in the anatomical region
and the
ultrasonic transducer unit, thereby permitting interrogation with reference to
the
anatomic landmark in the anatomical region by positioning the transducer unit
with
respect to the anatomical landmark. The computational unit can further
comprise a
display for showing the anatomical map.
Preferably, the positioning unit is selected from the group consisting of a
positioning unit that positions the transducer unit, a positioning unit that
positions the
anatomical region or a positioning unit that can position both. The
positioning unit can
be operated and designed for manual, computer operator or automatic operation.
The
positioning unit can be manually operated to interrogate an anatomical region,
such as
an ankle. Positioning units can be those devices known in the art or described
herein to
accomplish such functions.
In one embodiment the invention includes an ultrasonic system for tissue . __
ultrasonic interrogation for broadband ultrasonic attenuation, comprising:
a) a first ultrasonic transducer with a first axis of transmission through a
first
anatomical region to be interrogated and the first ultrasonic transducer is
adapted
for longitudinal transmission,
b) a second ultrasonic transducer with a second axis of transmission through a
second anatomical region to be interrogated and adapted for longitudinal
reception, wherein the first anatomical site and the second anatomical site
permit
monitoring broadband ultrasonic attenuation and speed of sound between the
first ultrasonic transducer and the second ultrasonic transducer,
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c) a positioning unit to position the first ultrasonic transducer with respect
to the
first anatomical region and to position the second ultrasonic transducer with
respect to the second anatomical region, and
d) a computational unit designed to manage ultrasonic signal transmission of
the
first ultrasonic transducer, to manage ultrasonic signal reception of the
second
ultrasonic transducer and to control the positioning unit.
The transducers are adapted for either longitudinal transmission or reception
or
both. Longitudinal transmission refers to transmission of signals between two
transducers. Longitudinal reception refers to reception of signals between two
transducers. Transducers or the computation unit can be adapted for such
transmission
and reception by including the pulse protocols, frequencies and analysis
methods.
Typically, the positioning system can independently position each transducer
to
establish a desired spatial relationship between the axis of transmission for
each
transducer, including a common axis of transmission. For example, the
positioning unit
can comprise an x, y positioner for the first ultrasonic transducer and the
second
ultrasonic transducer. Typically, the first axis of transmission is generally
the same axis
of transmission as the second axis of transmission. Preferably, the ultrasonic
system
includes a computational unit comprising a computer program product to
generate an
anatomic landmark to assist in reproducible positioning of the first
ultrasonic transducer
and the second ultrasonic transducer and the positioning unit comprises a z
positioner
controlled by the computational unit.
~.O METHODS FOR GENERATING OR IDENTIFYING ANATOMICAL LANDMARKS
The invention also includes an ultrasonic method for generating an anatomic
landmark for ultrasonic interrogation, comprising:
a) positioning, with respect to an anatomical region, an ultrasonic transducer
unit
comprising either 1 ) a first ultrasonic transducer that can transmit and
receive
signals or 2) a pair of ultrasonic transducers where a first member of the
pair is
designed to transmit signals and a second member of the pair is designed to
receive signals, and
b) interrogating the anatomical region with the ultrasonic transducer unit,
and
c) identifying an anatomic landmark in the anatomical region with an
ultrasonic
property of the anatomical region, and
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d) optionally storing the anatomic landmark in a storage device.
The ultrasonic method can further comprise the steps of comparing the location
and axis
of transmission of the ultrasonic transducer unit to the location of the
anatomic
landmark and positioning the ultrasonic transducer unit to produce an axis of
transmission generally through the anatomic landmark. Steps a, b, and c can be
optionally repeated. This can increase accuracy or permit close matching of
observed
landmarks with reference maps or landmarks. Each positioning step can be
performed
in relation to an anatomic lmdmark. The positioning steps are typically
performed to
generate an axis of transmission substantially through the anatomic landmark.
Although
the transmission axis can be in a predetermined coordinate or desired spatial
relationship with respect to the landmark. The positioning steps can be
performed to in
relation to a reference anatomic landmark of the anatomical region that is
stored in
retrievable form on a storage device.
In some embodiments, it will be desirable to generate anatomical maps and
landmarks, as well as images, with signals from multiple transmission and
detection
angles. Generally, it will be desirable to place the probe in a position that
is
substantially orthogonal to the object plane in order to measure layer
thickness
accurately. In many situations, it will be desirable to transmit a series of
pulses at
different transmission angles, usually about S to 10 degrees apart. This
permits
generating an image or alternatively a map or landmark from different
interrogation
paths. Typically, transmission angles can differ in 1, 2, 3, 4, 5, 6, 7, 8, 9
or 10 degree
increments or multiples thereof. Preferably, a series of transmission angles
will be used,
as measured with respect- to the object plane, such as 90, 85, 80, 75, 70, 65
and 60 _
degrees. It will be readily apparent to those skilled in the art that
transmission angles of
90, 95, 100, 105, 110, 115 and 120 degrees can also be used. In some
embodiments,
selection of the transmission angle is based on whether a common axis of
transmission
is desired.
In various embodiment of the invention, transmission angles can converge or
diverge from an ultrasonic source or sources. Generally, there is seldom a
limitation as
to whether convergent or divergent transmission angles can be used in the
invention.
Some applications will, however, operate more effectively by selecting the
appropriate
angle arrangement. To retain a narrower field of interrogation, a single
ultrasonic
source can be used at relatively small divergent angles, such as no more than
about a 20
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to 30 degree total divergence in transmission angles. For a wider field of
interrogation
multiple ultrasonic sources can be used with divergent angles. If a narrow
field of
interrogation is desired, multiple ultrasonic sources can be used with
convergent
transmission angles.
5 To vary transmission angles, typically a first pulse has a first
transmission angle
with respect to the object plane and a second pulse has a second transmission
angle with
respect to the object plane, wherein there is a predetermined divergent angle
between
the first and second pulse or a convergent angle between the first and second
pulse. The
predetermined divergent or convergent angles can be selected to improve the
10 measurement of a ultrasonic parameters generated in A scan or B scan. The
selection of
transmission angles typically takes into account the depth in the field where
the target
reflective layer (or layers) is likely to be located (target reflective layer
depth), the likely
thickness of the target reflective layer (target reflective layer thickness),
object
composition and distances between ultrasonic sources (if multiple sources are
used).
15 Generally, the total range of transmission angles oc will not be greater
than 45 degrees,
and preferably 30 degrees or less.
The divergent angle separates a first position and second position of an
ultrasonic source or sources and the first pulse has a centered first axis of
transmission
and the second pulse has a centered second axis of transmission, wherein the
first and
20 second axis do not converge. Usually the divergent angle between the first
and second
pulse is between S to 90 degrees, and preferably between about 5 and 20
degrees.
The convergent angle separates a first position and second position of an
ultrasonic source or sources and the first pulse has a centered first axis of
transmission
and the second pulse has a centered second axis of transmission, wherein the
first and
25 second axis converge. Usually the convergent angle between the first and
second pulse
is between 5 to 90 degrees, and preferably between about 5 and 20 degrees.
Different transmission angles can be accomplished by any method known,
developed in the art or in the future or described herein. Typically, the
invention
includes three different methods (with the corresponding devices) for varying
the
30 transmission angle: 1 ) mechanically changing position of the transducers)
with respect
to the plane of the tissue, 2) providing multiple transducers with
predetermined
positions that correspond to predetermined transmission angles and 3) steering
ultrasonic beams from multiple ultrasonic sources (typically arrays) with
predetermined
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firing sequences. For cost effective production of devices only one of these
methods
will typically be used in a device. If more sophisticated devices are desired,
such
methods can also be combined to gain the benefit of the different methods.
To vary transmission angles using a mechanical device, typically the first and
second pulses are from a first ultrasonic generator. The first generator has
at least a first
and a second position. The first and second position are mechanically
connected. The
generator is guided from the first position to the second position with a
mechanical
connection. The first and second position (or more positions for more
transmission
angles) for the ultrasonic generator can be connected using any connection
that changes
the transmission angle of the ultrasonic generator in an accurate and
controllable
fashion. Typically, a sweep through alI of the desired positions, either in
increments or
continuously, should be completed within about 0.02 to 2 seconds, preferably
within
200 to 500 milliseconds and more preferably within 20 to 200 milliseconds.
These time
values also apply to other methods of varying the transmission angle. Such a
device can
be mounted on or engaged by an x, y positioner to locate the tranducers at a
desired
anatomical region.
In one embodiment, the invention utilizes a mechanical connection comprising a
mechanical motor that can oscillate a generators) at least once from the first
to the
second position (or more positions) in order to vary the transmission angle.
This device
can be used to create maps, identify anatomical landmarks, and measure BUA or
SOS
or other ultrasonic methods described herein. The mechanical motor typically
provides
a frame time of oscillation from 10 to 2500ms. Any mechanical motor that can
produce
- - - a position change in such a time frame in response-to an electrical
command signal and
can be adapted for use in a hand-held probe can be preferably used to vary the
transmission angle of ultrasonic generators, such as crystals or arrays of
crystals. Such a
device can be mounted on or engaged by an x, y positioner to locate the
tranducers at a
desired anatomical region.
In one design the mechanical motor has at least a first and second magnet to
move the ultrasonic generator on a track, and the generator further comprises
a magnetic
source or magnetically attractive material that magnetically communicates with
the first
or second magnet to change the transmission angle. Magnetic switching of an
ultrasonic generator position is particularly desirable because the magnet can
be turned
off and on relatively rapidly, and directed to change polarity relatively
rapidly. Such
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magnetic systems can provide smooth position changes and relatively noise free
performance. The track can be any mechanical device that directs the
ultrasonic
generator between positions. In some instances the track will comprise a
groove that
engages the ultrasonic generator and permits the ultrasonic generator to pivot
around an
axis to allow for the probe to sweep across the desired transmission angles.
First and
second magnet refers to magnets that can be used to move an ultrasonic source
from a
first to a second position. Magnets may be permanent or induced by applying an
electric current to the appropriate electronic device. For example, an
electric current
can be applied to a wire arranged in a loop or coil-like configuration and the
magnetic
field created can be controlled by a predetermined electrical switch. The
current
induces a magnetic field that can be manipulated depending on the pattern of
applied
current or by the design of the coil or both. Additional magnets can be used
for
additional position for multiple placement.
In another embodiment, the invention utilizes permanently fixed ultrasonic
generators with different, individual transmission angles to accomplish
mapping,
anatomical landmarks, BUA or SOS, or other ultrasonic methods described
herein.
Typically, a first pulse is from a first ultrasonic generator and second pulse
is from a
second ultrasonic generator, wherein the first and second ultrasonic
generators are
permanently fixed in a first and a second position. More than two ultrasonic
generators
can be used as well but usually not more than about 10 ultrasonic generators
will be
used in this embodiment, unless they are arrays of crystals.
In another embodiment, the invention utilizes predetermined patterns of
ultrasonic source activation that result in different transmission angles to
accomplish
mapping, anatomical landmarks, BUA or SOS, or other ultrasonic methods
described
herein. For example, a predetermined pattern of ultrasonic source activation
can
comprise 1 ) a first series of trigger pulses that sequentially fires an array
of ultrasonic
crystals starting from a first end to a second end of the array and 2) a
series of trigger
pulses that sequentially fires the array from a second end to a first end of
the array. The
first series of pulses have a biased direction along a first portion of the
field of the
interrogated object, i.e. the beams are steered to one side of the field. This
sequence of
pulses can be repeated at different time frames in order to change the average
transmission beam angle. Similarly, the second series of pulses have a biased
direction
along a second portion of the field of the interrogated object, i.e. the beams
are steered
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to a second side of the field. This sequence of pulses can be repeated at
different time
frames in order to change the average beam angle. With linear arrays this
method
permits the use of either divergent or convergent transmission angles without
mechanically moving the ultrasonic source to change the transmission angle.
Averaged
beams obtained by this method with different transmission angles can then be
used to
calculate BUA or SOS or other ultrasonic methods as described herein.
As part of the predetermined pattern of ultrasonic source activation,
simultaneous triggering pulses may also be used in conjunction with sequential
firing
patterns. Simultaneous firing of the ultrasonic sources effectively provides a
series of
beams, which can be optionally averaged, to provide orthogonal probe position
relative
to a reference plane. When the ultrasonic source is orthogonal to the
object/tissue plane,
the transmission angle of simultaneously fired beams will be ninety degrees.
If the
probe has a non-orthogonal position, then the transmission will be more or
less than
ninety degrees. By comparing the signals generated from sequentially fired
pulses to
simultaneously fired pulses, the deviation from an orthogonal probe position
can be
calculated to accomplish mapping, anatomical landmarks, BUA or SOS or other
ultrasonic methods described herein. Comparison of ultrasonic parameter (e.g.
BUA or
SOS) from the averaged signals of both the sequentially generated pulses and
the
simultaneously generated pulses will be indicative of the difference in tissue
structure
ascertained at different transmission angles. If so desired, this information
can be
transmitted back to the operator, for instance on a monitor, to alert the
operator to tissue
abnormalities or status. Once the operator has evaluated the results, the
operator may
instruct the system to adjust the probe to achieve orthogonal probe alignment
for
interrogation of that particular tissue.
The trigger pulses described herein can be particularly optimized to enhance
measurement of BUA or SOS in vivo, such as in humans or other objects
described
herein. To steer a series of beams to create an averaged beam with a specific
transmission angle, each ultrasonic crystal is triggered with a lp.s to SOOp,s
delay
between the firing of each crystal. By increasing the delay between firing
each crystal,
the depth of interrogation and the transmission angle of the averaged beam can
be
changed. Ultimately, depth of interrogation will be limited by the dimensions
of the
transducer near and far field (Bushberg, J.T., Seibert, J.A., Leidholdt, E.M.,
Boone,
J.M., The Essential Physics of Medical Imaging 1-742 (1994)). The trigger
pulses are
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timed to delay, such as an exponential delay, the firing of the crystals
(crystals 1-5) over
a 15 sec time period. The firing sequence causes a delay across the array in
order to
steer to the target and provide an averaged beam (of five beams in this
example) with a
predetermined transmission angle illustrated as 75 degrees.
The following materials and methods are exemplary of the materials and
methods that can be used to achieve the results described herein. These
examples are for
illustrative purposes only, and are not to be construed as limiting the
appended claims.
One skilled in the art will readily recognize substitute materials and
methods.
General Materials and Methods:
In vivo ultrasonic measurements are performed using a prototype ultrasonic
system capable of measuring speed of sound and broadband ultrasonic
attenuation in the
heel region. The device is also capable of measuring distances between
different
acoustic/tissue interfaces using A-scan technique.
The ultrasonic system consists of two ultrasonic sources mounted on a U-shaped
plastic frame. A hinge is located in the center portion of the U-shaped
plastic frame that
allows for adjusting the distance between the ultrasonic transducers for each
individual
patient. The physical distance separating both transducers is registered for
each patient
using an electronic system that employs a potentiometer. The U-shaped plastic
frame is
connected to a plastic housing on which the patient can rest the fore- and mid-
foot and
in particular the heel comfortably. The ultrasonic sources are placed by the
operator on
the left and-the right side of the foot in the heel region. An ultrasonic gel
is used for
acoustic coupling. The operator adjusts the frame and the attached ultrasonic
sources
visually so that they are flush with the skin and near perpendicular to the
skin surface.
The ultrasonic system is designed with a central processing unit responsible
for
pulsing the ultrasonic transducers) and crystal(s), registering signals
returned from the
transducer, preamplification of the electronic signal, time gain compensation,
signal
compression, signal rectification, demodulation, and envelope detection,
signal
rejection, signal processing, analysis and display of SOS, BUA, and soft
tissue and bone
distance measurements. Transducers operate at a center frequency of 1 MHz.
However, transducer center frequency can be switched from 1 to 0.5 MHz. As the
interrogation frequency of the micro-transducer decreases, generally, the
ability to
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resolve reflective surfaces at deeper depths improves. The lower frequency is
used in
obese or edematous patients in whom tissue penetration with the 1 MHz probe is
insufficient.
With each measurement the device registers initially the physical distance
5 between both transducers. The device then measures (a) speed of sound, (b)
broadband
ultrasonic attenuation, and (c) soft tissue thickness on the medial and
lateral side of the
heel. Broadband ultrasonic attenuation is calculated by subtracting the
amplitude
spectrum of a patient from one obtained in a reference material (e.g. de-
gassed water).
As an alternative to ultrasonic distance measurements using A-scan technique,
10 ultrasonic measurements can also be performed using another prototype
system that is
capable of two-dimensional image acquisition and display using B-scan
technology in
addition to SOS and BUA measurements. This ultrasonic system also uses two or
more
ultrasonic sources mounted on a hinged, U-shaped plastic frame. The physical
distance
separating both transducers is registered for each patient using an electronic
system.
15 After positioning of the patient and the transducers and application of the
acoustic
coupling gel, data are acquired in B-scan mode. Two-dimensional gray-scale
images of
the various tissue layers are obtained. Images are displayed on a computer
monitor
attached to the scanner hardware.
Distance measurements are performed by saving a representative image
20 displaying the various tissue layers, e.g. skin, subcutaneous fat and bone,
on the display
monitor. A trained physician or operator identifies the various tissue
interfaces visually
and places cursors manually at the probe/skin and the soft tissue/bone or
other
interfaces. Software provided with the ultrasonic scanner is then used to
calculate the -
distance between the cursors. All measurements are expressed in mm.
25 All experiments performed on animal subjects (including humans) shall be
performed with the highest ethical and medical standards and in accordance
with the
relevant laws, guidelines and regulations of the relevant governing
jurisdictions) or
professional association(s), including, where appropriate, compliance under 45
CFR 46
relating to United States federal policy for the protection of human subjects.
Example 1: Computational Correction of Tissue Edema Induced Changes in Speed
of Sound and Broadband Ultrasonic Attenuation of the Calcaneus
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This example documents, among other things, that ultrasonic measurements of
speed of sound and broadband ultrasonic attenuation are significantly affected
by tissue
edema. Such edema is frequently encountered in a large variety of medical
conditions.
Patients with compromised cardiac function, compromised renal function,
compromised
hepatic function, or compromised vascular function frequently develop tissue
edema in
the lower extremities. This example also documents that the accuracy of speed
of sound
and broadband ultrasonic attenuation measurements can be improved by measuring
the
thickness of the soft tissue that overlies the calcaneus in the beam path and
by
correcting for the error in SOS and BUA of the calcaneus caused by such soft
tissue.
Speed of sound and broadband ultrasonic attenuation measurements are
performed in a 35 or 38 year old healthy male volunteer.
Ultrasonic measurements are performed using a prototype ultrasonic system that
is capable of two-dimensional image acquisition and display using B-scan
technology in
addition to SOS and BUA measurements. The volunteer's foot is placed in the
1 S ultrasonic system so that it rests inferiorly and posteriorly on the heel
pad of the device
(see FIG. 5C). The measurement site is marked on the skin with India ink on
the left
and right side of the heel. A small amount of acoustic coupling gel is applied
to the
volunteer's skin and the ultrasonic transducers are placed against the skin at
the .
measurement site.
Two-dimensional gray-scale images of the heel are obtained at the measurement
site. The distance from the probe/skin interface to the soft tissue/bone
interface, i.e. the
soft tissue thickness, is measured on the left and the right side of the heel
at the
measurement site. The sum of the soft tissue thickness measured on the left
and the
right side of the heel is calculated. SOS and BUA are measured in the same
location.
The volunteer's foot is removed from the ultrasonic device. The measurement
site at the medial and the lateral aspect of the heel is then cleaned with
iodine solution
for disinfection. A 20 cc syringe is then filled with 1 % Xylocaine solution
(Astra
Pharmaceuticals, Westborough, MA 01581). A sterile 25 Gauge needle is attached
to
the syringe. The needle is inserted into the subcutaneous tissue of the foot
and 1 cc of
Xylocaine solution is injected into the tissue at the measurement site on the
left side of
the heel followed by injection of lcc of Xylocaine solution on the right side
of the heel.
The volunteer's foot is placed back in the ultrasonic device. Transducers are
positioned at the measurement site on the left and right side of the heel as
described
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above and ultrasonic soft tissue distance measurements and measurements of SOS
and
BUA are repeated.
This experiment is repeated for multiple injection volumes. Injected volumes
are increased by lcc with each new experiment on each side up to a total
injected
volume of 5 cc on each side.
In this model of soft tissue edema, SOS can decrease by approximately 1-2
percent with increasing soft tissue thickness as is shown in FIG. 3A. BUA
values can
decrease by approximately i 0-20 percent with increasing soft tissue thickness
as is
shown in FIG. 4A. (Note that actual attenuation of broadband ultrasonic waves
increases as soft tissue thickness increases, while BUA values (dB/MHz)
decrease as
soft tissue thickness increases. This distinction is often not recognized in
the literature,
which leads to misleading or potentially misleading conclusions about the
effect of soft
tissue on actual attenuation of broadband ultrasonic waves and BUA values.)
While the
magnitude of these changes may vary depending on technical factors and
injection
technique, the model indicates that changes in soft tissue edema can alter SOS
and BUA
measurements of the calcaneus significantly. When this change in SOS or BUA is
related to the reference range of SOS and BUA values in normal volunteers, it
can be
equivalent to a quarter to one half of a standard deviation. This shows that
soft tissue
edema adds marked inaccuracy in determining a patient's fracture risk.
In some clinical situations, the relationship between soft tissue thickness
and
induced change in SOS and BUA may be relatively linear as is shown in FIGS. 3A
and
4A. The measured value of SOS and BUA that is obtained with the smallest
amount of
soft tissue edema, i.e. prior to injection of saline, approximates the true
SOS and BUA
of the calcaneus most closely. If the relationship is linear, a linear
correction factor can
be used to estimate true calcaneal SOS or BUA based on measured SOS or BUA,
ultrasonic measured soft tissue thickness in the edematous state
(Dede",atous)~ ~d
previously measured soft tissue thickness in the non-edematous state (Dm;~).
Estimated
true SOS (SOSn"e) can be defined as:
SOStrue = SOS~~ured ~' ~(Dedernatous - Drnin) ~ Ksos] [Eq. 1 ],
where SOSmeasured 1S the measured speed of sound, D is the sum of the soft
tissue
thickness measured on the left side and on the right side of the heel either
in the
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edematous (Dedematous) or the non-edematous state (Dm;n), and Ksos is a
correction factor
(in sec). Since the relationship between soft tissue thickness and speed of
sound is
approximately linear in this model, the correction factor Ksos can be
calculated as:
S KSOS - ~ (Dmax - Droin) / (SOS,I,easuredDrnax - SOS~asuredDmin) I [Eq. 2],
where D",~X is maximum tissue thickness, i.e. tissue thickness with maximum
edema,
Dm;" is minimum tissue thickness, i.e. tissue thickness in the non-edematous
state,
SOSr"easuredDmax is measured speed of sound at maximum tissue thickness and
IO SOSr"e~uredDmin is measured speed of sound at minimum tissue thickness.
Using Eq. 2,
Ksos equals 0.00037 in the current example shown in FIG. 3A for measurements
of
speed of sound. Using this correction factor Ksos, speed of sound can be
corrected for
soft tissue thickness as is shown in FIG. 3B. One skilled in the art will
readily
recognize substitute equations, including those for non-linear relationships,
such as
15 exponential, logarithmic, or polynomial functions.
Estimated true BUA (BUA~"e) can be defined as:
BUAn"e = BUAneasured ~- ~(Dedematous - Dmin) / KBUA] [Eq. 3],
20 where BUAmeasured is the measured broadband ultrasonic attenuation, D is
the
sum of the soft tissue thickness measured on the left side and on the right
side of the
heel either in the edematous (Dedematous) or the non-edematous state (Dm;~),
and KBUA is a
correction factor (in MHz m /dB ). Since the relationship between soft tissue
thickness
and broadband ultrasonic attenuation is approximately linear in this model,
the
25 correction factor KBUA can be calculated as:
KBUA ' ~ (Drnax - Dmin) / (BUA,t,easuredDmax - BUAmeas~redDmin) I [Eq. 4],
where DmaX is maximum tissue thickness, e.g, tissue thickness with maximum
30 edema, Dm;n is minimum tissue thickness, e.g. tissue thickness in the non-
edematous
state, BUAn,easuredDmax is measured broadband ultrasonic attenuation at
maximum tissue
thickness and BUA~asuredDmin is measured broadband ultrasonic attenuation at
minimum
tissue thickness. Using Eq. 4, KBUA equals 0.0014 in the current example shown
in FIG.
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4A for measurements of broadband ultrasonic attenuation. Using this correction
factor
KBUA, broadband ultrasonic attenuation can be corrected for soft tissue
thickness as is
shown in FIG. 4B. One skilled in the art will readily recognize substitute
equations,
including those for non-linear relationships, such as exponential,
logarithmic, or
$ polynomial functions..
The prophetic data presented in FIGURES 3B and 4B demonstrate that good
estimates of true SOS and true BUA in the non-edematous state can be achieved
using
equations 1-4.
As an alternative to equations 1 and 2, true SOS without influence of soft
tissue
contributions (SOStrue without soft tissue) can be calculated using equations
$ and 6, if the
relationship between soft tissue thickness and SOS is linear or close to
linear:
SOStrue without soft tissue = SOS~asured '~' FSOS x DSOSmeasured [Eq. $],
1$ where SOS~"easurea is the measured speed of sound, Dsosmeasurea is the sum
of the
soft tissue thickness measured on the left side and on the right side of the
heel at the
time of the speed of sound measurement, and Fsos is a correction factor (in
1/sec).
Since the relationship between soft tissue thickness and speed of sound is
approximately
linear in this model, the correction factor Fsos can be calculated as:
Fsos = ~ (SOS,-SOS2) / (D~ - D2) ~ [Eq. 6],
where SOS1 is speed of sound measured for a given soft tissue thickness D~,
and SOS2 is
speed of sound measured for a given soft tissue thickness D2.
2$ Using equations $ and 6 and the data shown in FIG. 3A, true SOS without
influence of soft tissue contributions (SOS~e without soft tissue) c~ be
calculated as follows:
Fsos = ~ (SOS-SOS2) / (D, - D2) ~ _
_ ~ (1$77 msec-~ - 1$$7 msec') / (0.016 m - 0.023 m) ~ _
= ~ 20 msec-~ / (-0.00? m) ~ _
= 28$7.1 sec ~
SOS~e without soft tissue = SOSn,easured '~ FSOS x DSOSmeasured
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= 1587 msec-' + 2857.1 sec' x 0.012 m =
= 1587 msec-' + 34.3 msec' -
= 1621.3 msec '
As an alternative to equations 3 and 4, true BUA without influence of soft
tissue
5 contributions (BUAtr"e w;tt,~ut sore tissue) can be calculated using
equations 7 and 8, if the
relationship between soft tissue thickness and BUA is linear or close to
linear:
BUAhue without soft tissue = BUAmeasured '~ FBUA x DBUAmeasured [Eq. 7],
10 where BUA",~asured is the measured broadband ultrasonic attenuation,
DBUAmeasured
is the sum of the soft tissue thickness measured on the left side and on the
right side of
the heel at the time of the broadband ultrasonic attenuation measurement, and
FBUA is a
correction factor (in dB / MHz m). Since the relationship between soft tissue
thickness
and broadband ultrasonic attenuation is approximately linear in this model,
the
15 correction factor FBA can be calculated as:
FBUA = I (BUAI-BUA2) / (D~ - D2) I [Eq. 8],
where BUA~ is broadband ultrasonic attenuation measured for a given soft
tissue
20 thickness DI, and BUA2 is broadband ultrasonic attenuation measured for a
given soft
tissue thickness D2.
Using equations 7 and 8 and the data shown in FIG. 4, true BUA without
influence of soft tissue contributions (BUA~"e ,~";~,out soft tissue) can be
calculated as
follows:
FBUA = I (BUA,-BUA2) / (D~ - D2) I =
= I (54.9 dB MHz ' - 49.8 dB MHz ' ) / (0.016 m - 0.023 m) I =
_ ~ 5.1 dB MHz' / (-0.007 m) I =
= 728.6 dB MHz' m'
3O BUAttue without soft tissue = BUAmeasured + FBUA x DBUAmeasured
= 59.5 dB MHz' + 728.6 dB MHz-' iri' x 0.012 m =
= 59.5 dB MHz' + 8.74 dB MHz' _
= 68.2 dB MHz '
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One skilled in the art will readily recognize substitute equations for
calculating
or estimating SOS and BUA, including those for non-linear relationships
between soft
tissue thickness and SOS or BUA, such as exponential, logarithmic, or
polynomial
functions.
Example 2: Correction of Tissue Edema Induced Changes in Speed of Sound and
Broadband Ultrasonic Attenuation of the Calcaneus using Look-Up Tables
This example documents, among other things, how a correction table for speed
of sound and broadband ultrasonic attenuation can be developed for various
thicknesses
of the soft tissue located within the ultrasonic beam path. Such a correction
table can be
particularly useful in a patient who has abnormally thick soft tissues, such
as a patient
with peripheral edema secondary to compromised cardiac, renal, hepatic, or
vascular
function. A correction table of SOS and BUA for soft tissue thickness like the
one
developed in this Example can be used as an alternative or an improvement to
the
corrections and derivations of the corrections presented in Example 1, i.e.
corrections
assuming linear, non-linear, exponential, logarithmic, polynomial, or other
functions.
One skilled in the art will readily recognize substitute materials and methods
to correct
speed of sound and broadband ultrasonic attenuation measurements for thickness
of the
soft tissue interposed in the beam path.
Speed of sound and broadband ultrasonic attenuation measurements are
performed in a volunteer, healthy young Caucasian females) less than 30 years
of age
who -has an ethically and medically established need for leg amputation. Such
a
volunteer would typically be subject to an advanced and operable osteosarcoma
in the
leg. The experimental specimen consists of a foot and calf extending to the
knee joint.
Skin, subcutaneous tissue, muscle tissue, fascia, bone, and all other tissue
in the
specimen are intact and have not been damaged by specimen preparation or other
extrinsic manipulation. All ultrasonic experiments are performed in the heat
chamber at
body temperature and immediately post amputation.
Prior to and after amputation, the specimen is subjected to magnetic resonance
imaging (MRI) using a 1.5 Tesla whole-body MRI system (Siemens Vision, Siemens
Medical Systems, Erlangen, Germany). Before the specimen is placed in the
magnet, the
site at which ultrasonic speed of sound and broadband ultrasonic attenuation
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measurements will be performed is marked on the skin on the medial and lateral
aspect
of the heel using India ink. Vitamin E capsules are then secured to the skin
over the
medial and lateral India ink skin mark. Vitamin E capsules are secured to the
skin using
adhesive tape. Vitamin E capsules are easily identified on MR images and mark
the
ultrasonic beam path on the MR images. The specimen is placed in a knee coil
and
advanced into the isocenter of the magnet. T1-weighted spin-echo images are
obtained
with a repetition time TR of 600 msec, an echo time TE of 20 msec, 2 numbers
of
excitations (NEX), a field of view of 14x14 cm, and a matrix consisting of 256
x 256
picture elements. Images are obtained in the axial, coronal, and sagittal
plane. The
two-dimensional MR images are reconstructed using the built in scanner
software and
are displayed on the scanner viewing console. The axial image that displays
the
medially and laterally placed Vitamin E capsules marking the ultrasonic beam
is
selected and the following distances are measured: (a) thickness of the
calcaneus in the
area of the ultrasonic beam path, (b) medial soft tissue thickness, i.e. sum
of
subcutaneous fat and muscle medially, (c) lateral soft tissue thickness, i.e.
sum of
subcutaneous fat and muscle laterally. These MRI distance measurements are
performed
using calipers provided with the scanner software that are manually placed at
the
various tissue interfaces. The sum of the thickness of the medial and the
lateral soft
tissue layer measured by MRI is calculated and is assigned baseline soft
tissue thickness
(DSOft tissue baseline) Such measurements can be correlated with the
ultrasonic results
obtained herein.
The specimen is removed from the MRI system and submitted to ultrasonic
scanning. Ultrasonic interrogation described herein is performed both pre- and
post-
operatively. Ultrasonic measurements are performed using a prototype
ultrasonic
system that is capable of two-dimensional image acquisition and display using
B-scan
technology in addition to SOS and BUA measurements. A small amount of acoustic
coupling gel is applied to the skin and the ultrasonic transducers are placed
against the
skin at the previously marked skin site at the medial and lateral aspect of
the heel.
Two-dimensional gray-scale images of the heel are obtained at the measurement
site. The distance from the probe/skin interface to the soft tissue/bone
interface, i.e. the
soft tissue thickness, is measured on the medial and the lateral side of the
heel at the
measurement site. The sum of the soft tissue thickness measured on the medial
and the
lateral side of the heel is calculated. SOS and BUA are then measured in the
same
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location. The measured SOS and BUA values are assigned as baseline SOS
(SOSbaseune)
and baseline BUA (BUAb~~;"e).
Tissue samples composed of skin, subcutaneous fat, and muscle are obtained
from the abdominal region of a beef carcass. The hair is removed from all
tissue
samples prior to cutting. Tissue samples are cut into slices with thicknesses
ranging
from 1-30 mm at 1 mm increments. Slices that are thinner than 5 mm are
composed
only of subcutaneous fat. Slices that are 5 mm and more thick are cut in a
fashion so
that they contain a muscle layer that does not exceed 3 mm in thickness in
addition to
skin and subcutaneous fat. Alternatively, after the operation fat tissue may
be obtained
from the amputated tissue.
The specimen is removed from the ultrasonic system. A 1 mm slice of bovine
tissue is placed at the medial aspect of the heel. The specimen along with the
slice of
bovine tissue secured to the medial measurement site is returned into the
ultrasonic
device, a small amount of acoustic coupling gel is applied medially and
laterally, and (a)
speed of sound, (b) broadband ultrasonic attenuation, and (c) medial and
lateral soft
tissue thickness are measured. Measured soft tissue thickness consists of both
peripheral
bovine and underlying human soft tissue. The sum of the soft tissue thickness
measured
on the medial and the lateral side of the heel is calculated.
The specimen is removed from the ultrasonic system. A 1 mm slice of bovine
tissue is placed at the lateral aspect of the heel in addition to the slice
previously placed
at the medial aspect of the heel. The specimen along with the slices of bovine
tissue
secured to the medial and lateral measurement site is returned into the
ultrasonic device,
a small amount of acoustic coupling gel is applied. medially and laterally,
and (a) speed - - _ . _.
of sound, (b) broadband ultrasonic attenuation, and (c) medial and lateral
soft tissue
thickness are measured. Measured soft tissue thickness consists of both
peripheral
bovine and underlying human soft tissue. The sum of the soft tissue thickness
measured
on the medial and the lateral side of the heel is calculated.
The experiment is repeated in a step-wise fashion while increasing first the
medial and then the lateral soft tissue thickness, each in 1 mm increments, by
using
thicker slices of bovine tissue up to a maximum of 30 mm of medial bovine
slice
thickness and 30 mm of lateral bovine slice thickness.
As the thickness of the soft tissue layers interposed in the ultrasonic beam
path
increases, speed of sound and broadband ultrasonic attenuation values decrease
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continuously. However, since baseline speed of sound and baseline broadband
ultrasonic attenuation prior to increasing soft tissue thickness above normal
levels are
known, correction factors for speed of sound and broadband ultrasonic
attenuation can
be calculated for individual soft tissue thicknesses similar to the methods
presented in
Example 1. Such correction factors can be stored in a "look-up table".
Alternatively,
such values may be obtained using the type of measurements in Example 1. Such
look-
up tables can be used in human subjects to correct speed of sound or broadband
ultrasonic attenuation measurements of the calcaneus for the thickness of the
overlying
soft tissue layer. Such look-up tables are particularly useful for patients
with
compromised cardiac, renal, hepatic, or vascular function with peripheral
edema. Such
look-up tables can be used in such patients to (a) correct for pathologic
increases in soft
tissue thickness resulting from tissue edema and to (b) correct for variations
in the
amount of edema and associated soft tissue thickness which can be seen with
worsening
of the patient's underlying medical condition or improvement of the patient's
underlying medical condition, for example due to medical intervention. Such
look-up
tables can also be used to correct for diurnal changes, e.g. small amount of
peripheral
edema and associated soft tissue thickness in the morning and large amount of
peripheral edema and associated soft tissue thickness in the evening.
Since soft tissue swelling can be asymmetrical, i.e. affect one side, medial
or
lateral, more than the other side, the experiment is repeated, with the slices
of bovine
tissue only applied to the medial side of the heel. In this model of
asymmetrical,
unilateral medial soft tissue edema, the experiment is repeated in a step-wise
fashion
while increasing the thickness of the medial soft tissue layer in 1 mm
increments from 1
mm up to a maximum of 30 mm. The same experiment is then repeated with the
slices
of bovine tissue only applied to the lateral side of the heel while increasing
the thickness
of the lateral soft tissue layer in 1 mm increments from 1 mm up to a maximum
of 30
As the thickness of the soft tissue layers interposed in the ultrasonic beam
path
increases, speed of sound and broadband ultrasonic attenuation decrease
continuously.
However, since baseline speed of sound and baseline broadband ultrasonic
attenuation
prior to increasing soft tissue thickness above normal levels are known,
correction
factors for speed of sound and broadband ultrasonic attenuation can be
calculated for
individual soft tissue thicknesses in this model of asymmetrical edema similar
to the
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methods presented in Example 1. Such correction factors for asymmetrical
medial or
lateral soft tissue edema can be stored in a "look-up table". Such look-up
tables can be
used in human subjects to correct speed of sound or broadband ultrasonic
attenuation
measurements of the calcaneus for the thickness of the overlying soft tissue
layer in
5 asymmetrical edema. Such look-up tables are particularly useful for patients
with
compromised cardiac, renal, hepatic, or vascular function and asymmetrical
peripheral
edema.
In another series of experiments, all overlying soft tissues are surgically
removed from the specimen's heel and the bony surface of the calcaneus is
exposed.
10 Speed of sound and broadband ultrasonic attenuation measurements of the
calcaneus are
repeated over the same measurement site used in the previous experiments.
Thus, true
speed of sound (SOS,rue) and true broadband ultrasonic attenuation (BUAtr"e)
of the
calcaneus are determined unaffected by any, not even normal, overlying soft
tissues.
The SOS and BUA measurements described above for bilateral symmetrical,
unilateral
15 asymmetrical medial, and unilateral asymmetrical lateral edema are repeated
using the
previously prepared slices of bovine tissue.
As the thickness of the soft tissue layers interposed in the ultrasonic beam
path
increases, speed of sound and broadband ultrasonic attenuation values decrease
continuously. However, since true speed of sound and true broadband ultrasonic
20 attenuation prior to increasing soft tissue thickness are known, correction
factors for
speed of sound and broadband ultrasonic attenuation can be calculated for
individual
soft tissue thicknesses similar to the methods presented herein. Example 1.
Such
correction factors can be stored in a "look-up table".--Such look-up tables
can-be used in -
human subjects to correct measured speed of sound or measured broadband
ultrasonic
25 attenuation of the calcaneus for the presence and thickness of any normal
or
pathologically enlarged overlying soft tissue layer. Such look-up tables
provide an
estimate of true speed sound and true broadband ultrasonic attenuation
independent of
overlying soft tissue thickness. Such corrections are particularly useful for
comparing
different individuals and populations, since SOS and BUA measurements
corrected in
30 this fashion will not be affected by normal variations in soft tissue
thickness or
pathologic increases in soft tissue thickness, e.g. in the presence of tissue
edema.
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Example 3: Correction of Tissue Edema Induced Changes in Speed of Sound of the
Calcaneus using Previously Published Data on SOS in Various Soft Tissues
This example documents, among other things, how speed of sound can be
corrected for variations in thickness of the soft tissue located within the
ultrasonic beam
path by measuring the thickness of the interposed soft tissue layers using A-
scan or B-
scan technology and by eliminating soft tissue induced changes in measured SOS
of the
calcaneus using previously known and published data for soft tissue SOS. Such
corrections are particularly useful in patients who have abnormally thick soft
tissues
such as patients with peripheral edema secondary to compromised cardiac,
renal,
hepatic, or vascular function. Corrections of measured SOS for soft tissue
thickness
like the one developed in this example can be used as an alternative or an
improvement
to the corrections and derivations of the corrections presented in Examples 1
and 2, i.e.
corrections assuming linear, non-linear, exponential, logarithmic or other
functions. One
skilled in the art will readily recognize substitute materials and methods to
correct speed
of sound and broadband ultrasonic attenuation measurements for thickness of
the soft
tissue interposed in the beam path.
Five patients with compromised cardiac function and peripheral edema are
selected. A trained physician examines all five patients clinically for visual
or palpatory
evidence of edema in the morning before 10 am and in the evening after 5 pm.
Edema
is clinically evaluated anterior to the tibia by visual inspection and manual
palpation.
Using standard clinical techniques (see Bates et al., J.B. Lippincott, 1995),
edema is
subdivided into 5 grades:
0.) absent,
1.) slight,
2.) mild,
3.) moderate, and
4.) severe.
Ultrasonic measurements are performed in each patient in the morning before 10
am and in the evening after S pm shortly after the clinical examination using
a prototype
ultrasonic system that is capable of two-dimensional image acquisition and
display
using B-scan technology in addition to SOS and BUA measurements. The patient's
foot
is secured in the ultrasonic device so that the heel of the foot rests on the
heel pad of the
device and the posterior aspect of the heel touches the back-wall of the
instrument (see
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also FIG. SC). The measurement site is marked on the skin with India ink on
the left
and right side of the heel. A small amount of acoustic coupling gel is applied
to the skin
and the ultrasonic transducers are placed against the skin at the measurement
site.
Two-dimensional gray-scale images of the heel are obtained at the measurement
site. The distance from the probe/skin interface to the soft tissue/bone
interface, i.e. the
soft tissue thickness, is measured on the left and the right side of the heel
at the
measurement site. The sum of the soft tissue thickness measured on the left
and the
right side of the heel (Dsort tissue) is calculated. SOS and BUA are then
determined in the
same location.
For determining SOS, the instrument measures initially the total travel time
of
the ultrasonic beam through the calcaneus and the medial and lateral soft
tissue (Ttota,).
Since the device registers the physical distance between the medial and the
lateral
transducer and since both are in contact with the skin medially or laterally,
the total
thickness of the heel (DheeO is known. Global speed of sound for combined bone
and
soft tissue components is thus calculated as:
SOSG~obal = l~hee~ / Z'cota~ (Eq. 9J
This measurement and calculation is widely used in most current ultrasonic
instruments used for measuring calcaneal speed of sound. However, it is
evident that not
only bone, but also soft tissue components contribute to the total travel time
which
explains why calcaneal SOS is artifactually lowered in the presence of soft
tissue
swelling.
Using equations 10-16 described below, true calcaneal SOS without alterations
resulting from soft tissue layers interposed in the ultrasonic beam path can
be
calculated. Total travel time through bone and soft tissues (Ttotai) c~ also
be described
as:
Ttotat = Tcalcaneus '~' Tsoft tissue [Eq. 10],
where T~aica~eus is the travel time of the ultrasonic beam through the
calcaneus
and Tso~ tiss"e is the travel time of the ultrasonic beam through the soft
tissues medial and
lateral of the calcaneus. Thus, T~aicaneus is defined as:
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Tcalcaneus - Ttotal - Tsofi tissue [Eq. 11 ).
Tsoft tissue is defined as:
Tsoft tissue - Dsoft tissue ~ S~Ssoft tissue EEq. 12~
Dsoct tissue is measured using A-scan or B-scan technology (see also Examples -
General Materials and Methods) and represents the sum of soft tissue thickness
medial and lateral to the calcaneus. SOSsoft tissue is known for different
soft tissues from
the literature (see Goss et al., J. Acoust. Soc. Am., 1978). For example,
speed of sound
of human fat tissue has been reported to be 1479 m/sec at 37° Celsius
(see Goss et al., J.
Acoust. Soc. Am., 1978). Thus, Tso~ tissue can be calculated by measuring
Dsort tissue using
A-scan or B-scan technology and by using previously published data for SOSsoft
tissue.
Since Tto,~, has been measured and Tson tissue has been calculated using Eq.
12, T~aicaneus
can be determined using Eq. 11.
The thickness of the calcaneus (D~a,~aneus) can be determined using the
following
equation:
Dcalcaneus = Dheel - Dsofttissue ~Ed. 13~.
Thus, true calcaneal speed of sound without any soft tissue interference is
defined as:
SOScai~neus - Dcalcaneus ~ Tcalcaneus [Eq. 14j, Or
SOScalcaneus = Dheel - Dsoft tissue ~ Ttotat - Tsoft tissue [Eq. 15], Or
S~Scalcaneus = Dheel - Dsoft tissue ~ (Ttotal - Dsoft tissue ~ S~Ssoft tissue)
Clinical examination in all 5 patients will typically show that peripheral
edema
has increased by the evening when compared to morning. Global speed of sound
for
combined bone and soft tissue components will be typically decreased in all S
patients
in the evening when compared to the morning measurement because of the
increase in
tissue edema and associated soft tissue swelling. Thus, global speed of sound
measurements are subject to diurnal changes dependent on the amount of edema
and
soft tissue swelling present. True calcaneal speed of sound calculated as
described in
Eq. 10-16, however, shows only mild variation for each patient between morning
and
evening measurements indicating that this parameter is less dependent on
tissue edema
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and provides a more accurate description of bone mineral density and structure
of the
calcaneus.
Example 4: Correlation of Speed of Sound and Broadband Ultrasonic Attenuation
of the Calcaneus with Calcaneal Bone Mineral Density Measurements Assessed by
Dual X-Ray Absorptiometry in Patients with Peripheral Edema before and after
Correction for Soft Tissue Thickness
This example documents, among other things, that correlations between speed of
sound or broadband ultrasonic attenuation and bone mineral density (BMD) of
the
calcaneus measured by dual x-ray absorpiometry (DXA) deteriorate in the
presence of
soft tissue edema in patients with compromised cardiac function, compromised
renal
function, compromised hepatic function, or compromised vascular function. This
example documents also that correlations between speed of sound or broadband
ultrasonic attenuation and BMD of the calcaneus measured by DXA improve when
SOS
and BUA measurements are corrected for the thickness of the soft tissue that
overlies
the calcaneus in the ultrasonic beam path.
Twenty patients with compromised cardiac function and peripheral edema are
studied with speed of sound and broadband ultrasonic attenuation measurements
of the
calcaneus and with bone mineral density measurements of the axial and
peripheral
skeleton using dual x-ray absorptiometry.
Ultrasonic measurements are performed in each patient using a prototype
ultrasonic system that is capable of two-dimensional image acquisition and
display
using B-scan technology in addition to SOS and BUA measurements. The patient's
foot
is secured in the ultrasonic device so that the heel of the foot rests on the
heel pad of the
device and the posterior aspect of the heel touches the back-wall of the
instrument (see
also FIG. 5C). The measurement site is marked on the skin with India ink on
the left
and right side of the heel. A small amount of acoustic coupling gel is applied
to the skin
and the ultrasonic transducers are placed against the skin at the measurement
site.
Two-dimensional gray-scale images of the heel are obtained at the measurement
site. The distance from the probe/skin interface to the soft tissuelbone
interface, i.e. the
soft tissue thickness, is measured on the left and the right side of the heel
at the
measurement site. The sum of the soft tissue thickness measured on the left
and the
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right side of the heel (D~~ tissue) is calculated. SOS and BUA are then
measured in the
same location.
Dual x-ray absorptiometry (DXA) is performed using a Lunar Expert DXA
system (Lunar Corporation, 313 West Beltline Hwy., Madison, WI 53713). In each
5 patient, DXA measurements are performed in the following anatomic regions:
- In the lumbar spine in AP projection extending from lumbar vertebral
level 1 to lumbar vertebral level 4.
- In the lumbar spine in lateral projection extending from lumbar vertebral
level 2 to lumbar vertebral level 4 or the next higher lumbar vertebral
10 level that is not superimposed by the iliac crest in the lateral
projection;
L2 is excluded from the analysis in those patients in whom ribs are
superimposed on this vertebral body.
- In the hip, measuring the intertrochanteric region and the region called
"Ward's triangle".
15 - In the distal radius.
- In the calcaneus.
DXA measurements in the calcaneus are performed in the same region that is
evaluated with speed of sound and broadband ultrasonic attenuation
measurements.
Bone mineral density (BMD) measurements in these anatomic regions are
expressed as
20 mg/cm2.
Correlations between DXA and SOS and BUA improve when soft tissue
thickness is measured ultrasonographically and SOS and BUA are corrected for
soft
tissue thickness using the methods and devices described in Examples 2 and 3.
25 Example 5: Correction for Edema-Induced Changes in Ultrasonic Probe
Position
and Its Influence on In-Vivo Reproducibility of Calcaneal Speed of Sound and
Broadband Ultrasonic Attenuation
This example shows among other things that the presence of peripheral edema
does not only affect soft tissue thickness in the beam path thereby altering
SOS and
30 BUA directly (see Examples 1-4), but also affects ultrasonic probe position
relative to
the underlying bone. This examples documents that edema induced changes in
ultrasonic probe position over the calcaneus and general variations in
ultrasonic probe
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position over the calcaneus reduce short-term and long-term in vivo precision
of SOS
and BUA measurements.
Twenty patients with compromised cardiac performance and peripheral edema
are selected for the study. SOS and BUA measurements are performed at
different
times in the day on two different days: In the morning on day 1 before 9 am
and in the
evening on day 2 after 6 pm. At each time interval, the degree of peripheral
edema is
assessed clinically by visual inspection and manual palpation. Using standard
clinical
techniques (see Bates et al., J.B. Lippincott, 1995), edema is subdivided into
5 grades:
0.) absent,
l.) slight,
2.) mild,
3.) moderate, and
4.) severe.
Ultrasonic measurements are performed in each patient using a first prototype
ultrasonic system that is capable of two-dimensional image acquisition and
display
using B-scan technology in addition to SOS and BUA measurements. The patient's
foot
is secured in the ultrasonic device so that the heel of the foot rests on the
heel pad of the
device and the posterior aspect of the heel touches the back-wall of the
instrument (see
also FIGS. 5A and 5B). A small amount of acoustic coupling gel is applied to
the skin
and the ultrasonic transducers are placed against the skin at the measurement
site.
Two-dimensional B-mode gray-scale images of the heel are obtained at the
measurement site using this first prototype system. The distance from the
probe/skin
-- interface to the soft tissue/bone interface, i.e. the soft tissue
thickness, is measured on
the left and the right side of the heel at the measurement site. The sum of
the soft tissue
thickness measured on the left and the right side of the heel (Dsoa tissue) is
calculated.
SOS and BUA are then measured in the same location yielding SOSmeasUrea and
BUAmeasured. Measured SOS and BUA are then corrected for soft tissue thickness
using
methods and techniques similar to those described in Examples 2 and 3 thereby
yielding SOS~one~ced and BUA.~o~.ecc~d. The prototype ultrasonic system used
for this part
of the experiment does, however, not correct for changes in the thickness of
the inferior
and posterior heel pad secondary to edema.
SOS and BUA measurements are then repeated using a second, different
prototype ultrasonic system. This second system is capable of identifying the
posterior
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contour and the inferior contour, e.g.the bright, echogenic cortex, of the
calcaneus on
the B-scan images. Using these landmarks, the system positions the ultrasonic
transducers automatically over a predefined region in the calcaneus, e.g. 1.5
cm anterior
to the posterior calcaneal cortex and 1.5 cm superior to the inferior
calcaneal cortex. In
this fashion, the ultrasonic transducers are reproducibly positioned over the
same
measurement site in the calcaneus regardless of changes in the thickness of
the posterior
and inferior heel soft tissue pad (see also FIG. 5C and SD).
Two-dimensional B-mode gray-scale images of the heel are then obtained at the
measurement site using the second prototype ultrasonic system. The distance
from the
probe/skin interface to the soft tissue/bone interface, i.e. the soft tissue
thickness, is
measured on the left and the right side of the heel at the measurement site.
The sum of
the soft tissue thickness measured on the left and the right side of the heel
(Dso~ t~ss~e) is
calculated. SOS and BUA are then measured in the same location yielding
SOSmeas"Ted
and BUA~~"red. Measured SOS and BUA are then corrected for soft tissue
thickness
1 S using methods and techniques similar to those described in Examples 2 and
3 thereby
yleldlrig SOSco,rected ~'1d BUAcorrected.
In-vivo reproducibility between am and pm measurements is better with the
second ultrasonic system that adjusts probe position relative to the posterior
and the
inferior cortex of the calcaneus than with the first prototype system with
fixed probe
position relative to skin/patient/heel surface. In-vivo reproducibility is
best when (a)
probe position is adjusted relative to the bony landmarks of the calcaneus,
e.g. posterior
and inferior cortex of the calcaneus, and (b) SOS",eas"red and BUAn,e~"r~, are
corrected
for medial and lateral soft tissue thickness thereby yielding SOSeo".ee~d and
BUA~o".eeted
(see also Examples 2 and 3).
Example 6: Correction for Edema-Induced Changes in Ultrasonic Probe Position
and Its Influence on In-Vivo Reproducibility of Calcaneal Speed of Sound and
Broadband Ultrasonic Attenuation before and after Diuretic Therapy
The experimental design used in this example is identical to that shown in
Example 5. However, rather than assessing the influence of diurnal changes in
tissue
edema between morning and evening measurements, twenty patients with
compromised
cardiac performance and peripheral edema are studied prior to and two weeks
after
initiation of diuretic therapy.
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78
The results show that in-vivo reproducibility of SOS and BUA is better when
the
ultrasonic system is capable of adjusting probe position relative to the
anatomic
landmarks, e.g. posterior and inferior cortex, of the calcaneus than with an
ultrasonic
system where the probe position is fixed relative to skin/patient/heel
surface. In-vivo
reproducibility is best when (a) probe position is adjusted relative to the
bony landmarks
of the calcaneus, e.g. posterior and inferior cortex of the calcaneus, and (b)
SOS",easurea
and BUA~"e~"rea are corrected for medial and lateral soft tissue thickness
thereby
yielding SOS~onectea and BUA~ort~tea (see also Examples 2 and 3).
PUBLICATIONS
U.S. PATENT
DOCUMENTS
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All documents and publications, including patents and patent application
documents, are herein incorporated by reference to the same extent as if each
publication were individually incorporated by reference.
