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Patent 2391289 Summary

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(12) Patent Application: (11) CA 2391289
(54) English Title: DYNAMIC THRESHOLDING OF SEGMENTED DATA SETS AND DISPLAY OF SIMILARITY VALUES IN A SIMILARITY IMAGE
(54) French Title: SEUILLAGE DYNAMIQUE D'ENSEMBLES DE DONNEES SEGMENTEES ET AFFICHAGE DES VALEURS DE SIMILARITE D'UNE IMAGE
Status: Dead
Bibliographic Data
(51) International Patent Classification (IPC):
  • G06T 5/50 (2006.01)
  • G06T 5/00 (2006.01)
  • G06T 5/20 (2006.01)
(72) Inventors :
  • WYMAN, BRADLEY T. (United States of America)
  • STORK, CHRISTOPHER L. (United States of America)
(73) Owners :
  • CONFIRMA, INC. (United States of America)
(71) Applicants :
  • CONFIRMA, INC. (United States of America)
(74) Agent: OYEN WIGGS GREEN & MUTALA LLP
(74) Associate agent:
(45) Issued:
(86) PCT Filing Date: 2000-11-24
(87) Open to Public Inspection: 2001-05-31
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2000/032204
(87) International Publication Number: WO2001/039123
(85) National Entry: 2002-05-10

(30) Application Priority Data:
Application No. Country/Territory Date
60/167,411 United States of America 1999-11-24

Abstracts

English Abstract




A method for image processing of magnetic resonance measurements to generate
object-specific enhanced display images, including obtaining magnetic
resonance measurements from an MRI apparatus; generating score data based on
the magnetic resonance measurements; and modifying the score data to produce
an enhanced image. Modifying the score data can include applying a convolution
filter, automatically generating a score data rejection threshold, and
modifying the score data to dynamically alter the rejection threshold to
produce a dynamically-enhanced image. The method provides tissue segmentation
results that are self-normalized, avoiding object and scanner dependencies in
the generation of MRI images.


French Abstract

L'invention concerne une technique de traitement d'image de mesures par résonance magnétique, destinée à générer des images améliorées d'un objet spécifique, consistant à obtenir des mesures par résonance magnétique d'un appareil IRM, à générer des données de valeur à partir de ces mesures, et à modifier ces données de valeur afin de produire une image améliorée. La modification des données de valeurs consiste à appliquer un filtre de convolution, à générer automatiquement un seuil de réjection des données de valeur, et à modifier les données de valeur afin de modifier dynamiquement le seuil de réjection et produire une image améliorée dynamiquement. Cette technique permet d'obtenir des résultats de segmentation des tissus qui sont autonormalisés, évitant ainsi les dépendances de l'objet et du numérisateur dans la génération d'images IRM.

Claims

Note: Claims are shown in the official language in which they were submitted.



CLAIMS

1. A method for establishing and applying an automatic threshold
determination to a data sample, the method comprising:
collecting a plurality of data elements representative of the properties of an
object;
obtaining a training set composed of a group of the data elements;
measuring the extent of similarity among the data elements in the training set
to determine the maximum distance between the individual data elements in the
group;
setting a threshold distance based on a measure of similarity between the
pixels in the group;
comparing the thresholded measure of similarity between the data elements in
the training set and test data elements not in the training set; and
classifying the test data element as a member of a class when measured
similarity between the test data element and the training set is less than or
equal to the
threshold value.
2. The method of claim 1, wherein measuring the extent of similarity
comprises determining the maximum Euclidean distance among the data elements
in the training
set.
3. The method of claim 2, wherein determining the maximum Euclidean
distance comprises:
calculating the distance using multivariate computational methods.
4. A method for determining and applying object-specific threshold
parameters to magnetic resonance measurements, the method comprising:
obtaining magnetic resonance measurements of an object from an MRI
apparatus;
generating an array of pixels from the magnetic resonance measurements for
displaying an image, including producing a training set comprising one or more
training
samples, the training set being formed from a plurality of congruent first
images of a training

32



region of the object, each first image being produced using an MRI pulse
sequence different
from the pulse sequences used to produce the ether first images;
producing a data set comprising a plurality of test data samples, the test
data set
being formed from a plurality of congruent second images of a test data region
of the same
object, the second images being produced using the same MRI pulse sequences as
the first
images;
generating score data for each pixel in the array of pixels; and
modifying the score data to produce an enhanced, object-specific image.
5. The method of claim 4, wherein modifying the score data comprises
automatically generating a score data rejection threshold.
6. The method of claim 4, wherein modifying the score data comprises
dynamically altering the score data to produce a corresponding dynamically-
enhanced image.
7. The method of claim 4, wherein modifying the score data comprises
automatically generating a score data rejection threshold.
8. The method of claim 4, wherein modifying the score data further
comprises dynamically altering the automatically-generated rejection threshold
to produce a
dynamically-enhanced image.

33


Description

Note: Descriptions are shown in the official language in which they were submitted.



CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
DYNAMIC THRESHOLDING OF SEGMENTED DATA SETS AND DISPLAY
OF SIMILARI~'Y VALUES IN A SIMILARITY IMAGE
TECHNICAL FIELD
The present invention pertains to a method for establishing and applying
thresholds to classified data. This invention pertains to a method to
automatically or
dynamically derive and display the acceptance threshold used to determine the
sufficiency of
similarity between the training set and a test sample.
BACKGROUND OF THE INVENTION
Pattern recognition involves the division of a set of samples into a number of
classes, based on measurements made on one or more properties of the samples.
The set of
samples within a given class are similar in terms of their measurement values,
which are
reflective of these samples' characteristics. Pattern recognition methods can
be categorized
into two broad classes: (a) supervised techniques, which utilize a priori
knowledge or
assumptions about the class membership of a set of samples to develop a
classification rule so
as to predict the class membership of unknown samples, and (b) unsupervised
techniques,
which without making a priori assumptions about the data, identify the class
memberships of
samples within the data set.
Pattern recognition is commonly performed in several disciplines, including
geology, chemistry, cytology, medical imaging, as well as banking and
marketing. The types
of samples on which pattern recognition is performed vary widely across
disciplines. While
the types of samples may differ across disciplines, the basic purpose of
pattern recognition
remains constant across all fields - to separate samples into logical groups
where each group
has distinct, measurable properties.
In supervised pattern recognition, given two or more samples of known class,
hereby referred to as the training set, and a sample of unknown class, hereby
referred to as
the test sample, one compares the measurement value or values of a test sample
to the
corresponding measurement values of a training set to determine if sufficient
similarity exists
to consider the test sample as being within the same class as the training
set.


WO 01/39123 CA 02391289 2002-05-to pCT/US00/32204
On the other hand, in unsupervised pattern recognition, the samples are
divided into classes based on measures of similarity between samples in a data
set without
any prior designation of class membership of any data.
U.S. Patent No. 5,003,979 describes a system for the detection and display of
lesions in breast tissue, using magnetic resonance imaging (MRI) techniques.
In one
described example, three different types of images are obtained for a given
region, and the
pixels of the image are then classified by comparing their intensity patterns
to known patterns
for pure tissue types, such as fat, cyst or cancer. The patent indicates that
three specific types
of images are adequate for statistically separating MR images of breast fat,
cyst, carcinoma
and fibroadenoma.
Applicants have found that in many cases, comparison of the pattern of
intensities of
a patient's tissue to a universal set of standard patterns for different
tissue types does not
produce results of sufficient accuracy. The basic problem appears to be that
there is too much
variability from one patient to the next, as well as from one MRI machine to
the next, to
apply a universal set of patterns to all patients. For this reason, the use of
standard patterns
does not result in the high degree of confidence that one must have in order
to forego a more
certain diagnostic technique, such as biopsy. For this reason, cancer
diagnosis based on MRI
has not yet achieved widespread acceptance. A problem that occurs frequently
in cancer
treatment is detecting when a primary tumor has spread to other sites in the
patient's body, to
produce so-called secondary tumors, known as metastases, at those sites.
Detection and
correct identification of metastases, using MRI or other imaging techniques,
is often
complicated by the fact that a remote lesion discovered during staging could
represent either
a metastasis or a benign incidental finding. A number of benign lesions (such
as hepatic
hemangiomas and non-functioning adrenal adenomas) occur as frequently in
patients with a
known primary tumor as they do in the general population.
Resolving this dilemma requires additional imaging or biopsy, but often
significant
uncertainty persists. Biopsy may expose the patient to substantial risk when
the lesion is in
the brain or mediastinum, or when the patient has impaired hemostasis. Even
when biopsy
does not present a significant risk to the patient, it may be technically
challenging, such as
sampling focal lesions in vertebral marrow.
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WO 01/39123 CA 02391289 2002-05-10 pCT/US00/32204
SUMMARY OF THE INVENTION
A method for establishing and applying an automatic threshold determination
to a test sample is provided. A method of displaying similarity images is also
provided.
According to principals of the present invention, data are collected from an
object to be studied. The data which have been collected are formed into a
data set which is
composed of a plurality of individual data elements.. The data elements
represent
corresponding locations in the object under investigation, with one or more
properties
collected for each data element. Some data within this set are segmented into
classes, using
either a supervised or an unsupervised segmentation technique.
After the initial segmentation has occurred, one or more of the resulting
classes is selected. A training data set within this chosen class of interest
is created. An
acceptance threshold is automatically created based on the properties of the
training set.
Using this automatic threshold as a standard, all data elements in the object
are classified. By
definition, data elements not in the training set are designatedas test
samples. The test
samples are compared to the data in the training set. If a test sample is very
similar to the
training set, so as to have a distance value that is less than or equal to the
automatic threshold,
it is determined to belong to the same class as the training set. If the test
sample has a
distance value which exceeds the automatic threshold, it is determined to not
belong to the
same class as the training set, and is placed in a different class. The
automatic threshold is a
custom generated number that has a different value for each training set and
thus uniquely
characterizes a subset of data elements within an object or patient. The
automatic threshold
therefore provides an improved analysis of the data because it is customized
to each
individual patient's own medical and physical characteristics.
One or more classes may be created which contain test samples that are
similar to the training set, but are not sufficiently similar to be considered
within the same
class as the training set. The new class or classes may contain a range of
test samples, some
of which are more similar to the training set than other test samples. The new
classes are
displayed in a manner to show the similarity that these data elements have to
the training set
and to display the range of similarity relationships among the test samples
and the training
set.
According to one embodiment of the invention, the similarity values of the
test
samples to the training set are displayed on a color scale. All of the test
samples that have
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CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
values most similar to the training set are depicted with a single color.
Accordingly, all test
samples that have values that are next most similar to the training set are
depicted with a second
color different from that assigned to the most similar set of test samples.
This multicolor
display of similarity values may be used to depict many different levels of
similarity, if desired.
The images are produced using magnetic resonance imaging (MRI) which
includes a variety of different pulse sequences and types of pulses. The
images are displayed
on a monitor composed of an array of pixels. On the display, the region of
interest appears as a
set of pixels in a particular location. Using the display as a guide, a user
selects a region of
interest to be studied with more detail. An initial segmentation of tissues
within the region of
interest is carried out on the imager-derived data to determine the number of
distinct tissues in
the region. After the initial segmentation is performed, the user selects one
or more of the
classes of tissue within the region of interest to study in more detail. A
training set is created
for each selected tissue class within the region of interest. The similarity
among the data
elements in the training set is determined using the maximum nearest neighbor
distance among
the training samples. From this, a classification threshold is established
that is set as the first
threshold for the maximum distance for a test sample to be considered to be in
the same class as
the training set. The distance between each test sample and its nearest
neighbor in the training
set is determined. The test sample is accepted as a member of the same class
as the training set
when the distance of the test sample is less than or equal to the
classification threshold distance.
In accordance with another embodiment of the present invention, a method for
applying a patient-specific threshold parameter is provided. The method
includes using an
MRI apparatus to generate image data sets and to produce a training set and a
test set, as
described above; measuring the extent of similarity between the pixels in the
training set and
each test sample to determine a threshold distance for inclusion of pixels in
a display class;
and then dynamically varying the classification threshold distance.
In accordance with another aspect of the foregoing embodiment, the method
includes displaying an image associated with the display class of pixels and
dynamically
altering the display of the image by dynamically varying the threshold value
that changes the
number of data elements in the class of interest. The display resulting from
the dynamic
varying of the threshold may be refreshed after each threshold change or
displayed in "real
time" meaning the display changes as the threshold is changed.
4


CA 02391289 2002-05-10
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The invention will be described in one embodiment in the context of data from
MRI as one example. The invention can be applied to the display of any image
data collected
by any acceptable technique, such as NMR, x-ray, computed tomography (CAT)
scan,
positron emission tomography (PET) scan, nuclear imaging, and other types or a
combination
of data from two or more of the techniques,.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is an isometric view of a known data collection apparatus which may
be used to collect image data for later processing according to the present
invention.
Figure 2 is a functional block diagram illustrating the steps in automatic
guided specific tissue segmentation method.
Figure 3 is a flowchart illustrating the steps performed in determining the
class
membership of a test sample.
Figure 4 is a functional block diagram illustrating one technique to calculate
and display similarity values.
Figures SA and SB are displays of an MRI image without and with use of the
invention, respectively.
Figures 6A and 6B illustrate a similarity image according to the present
invention as compared to a binary thresholded image, respectively.
Figures 7A and 7B illustrate dynamically varying the classification threshold
according to the present invention.
Figures 8A, 8B and 8C are screen views that a user of the invention may see
when comparing images using the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Figure 1 is a known sensor and data collection device as described in U.S.
Patent No. 5,644,232. It illustrates one technique by which data can be
collected for analysis
according to the principles of the present invention.
Details of magnetic resonance imaging methods are disclosed in U.S. Patent
No. 5,311,131, entitled, "Magnetic Resonance Imaging Using Pattern
Recognition"; U.S.
Patent No. 5,644,232, entitled, "Quantitation and Standardization of Magnetic
Resonance
Measurements"; and U.S. Patent No. 5,818,231, entitled, "Quantitation and
Standardization
5


CA 02391289 2002-05-10
WO 01/39123 PCT/LTS00/32204
of Magnetic Resonance Measurements." The above-referenced three patents are
incorporated in their entirety herein by reference. The technical descriptions
in these three
patents provide a background explanation of one environment for the invention
and are
beneficial to understand the present invention.
Pattern recognition is utilized in several disciplines and the application of
thresholding as described with respect to this invention is pertinent to all
of these fields.
Without the loss of generality, the examples and descriptions will all be
limited to the field of
magnetic resonance imaging (MRI) for simplicity. Of particular interest is the
application of
pattern recognition technology in the detection of similar lesions such as
tumors within
magnetic resonance images. Therefore, additional background on the process of
MRI and the
detection of tumor using MRI is beneficial to understand the invention.
Magnetic resonance (MR) is a widespread analytical method used routinely in
chemistry, physics, biology, and medicine. Nuclear magnetic resonance (NMR) is
a chemical
analytical technique that is routinely used to determine chemical structure
and purity. In
I S NMR, a single sample is loaded into the instrument and a representative,
multivariate,
chemical spectrum is obtained. The magnetic resonance method has evolved from
being only
a chemical/physical spectral investigational tool to an imaging technique,
MRI, that can be
used to evaluatecomplex biological processes in cells, isolated organs, and
living systems in a
non-invasive way. In MRI, sample data are represented by an individual picture
element,
called a pixel, and there are multiple samples within a given image.
Magnetic resonance imaging utilizes a strong magnetic field for the imaging
of matter in a specimen. MRI is used extensively in the medical field for the
noninvasive
evaluation of internal organs and tissues, including locating and identifying
benign or
malignant tumors.
As shown in Figure 1, a patient 20 is typically placed within a housing 12
having an MR scanner, which is a large, circular magnet 22 with an internal
bore large
enough to receive the patient. The magnet 22 creates a static magnetic field
along the
longitudinal axis of the patient's body 20. The magnetic field results in the
precession or
spinning of charged elements such as the protons. The spinning protons in the
patient's
tissues preferentially align themselves along the direction of the static
magnetic field. A
radio frequency electromagnetic pulse is applied, creating a new temporary
magnetic field.
The proton spins now preferentially align in the direction of the new
temporary magnetic
6


WO 01/39123 CA 02391289 2002-05-10 pCT/US00/32204
field. When the temporary magnetic field is removed, the proton spin returns
to align with the
static magnetic field. Movement of the protons produces a signal that is
detected by an antenna
24 associated with the scanner. Using additional magnetic gradients, the
positional information
can be retrieved and the intensity of the signals produced by the protons can
be reconstructed
into a two or three dimensional image.
The realignment of the protons' spin with the original static magnetic field
(referred to as relaxation) is measured along two axes. More particularly, the
protons
undergo a longitudinal relaxation (T~) and transverse relaxation (T2). Because
different
tissues undergo different rates of relaxation, the differences create the
contrast between
different internal structures as well as a contrast between normal and
abnormal tissue. Thus,
the signal intensity is proportional to a combination of the number of
protons, the T, and the
TZ properties of the tissue. Proton density weighted images generally
emphasize differences
in the number of protons between different tissues, while T,-weighted images
generally
emphasize the difference in T~ relaxation times between different tissues.
Similarly,
TZ-weighted images emphasize the difference in TZ relaxation times between
different tissues.
By manipulating the parameters of the MR scanner, an operator can produce
images that are
dominated by T~ or TZ relaxation (i.e., T~-weighted and TZ-weighted images) or
proton
density. In addition to T~, T2, and proton density, variations in the sequence
selection permit
the measurement of chemical shift, proton bulk motion, diffusion coefficients,
and magnetic
susceptibility using MR. The information obtained for the computer guided
tissue
segmentation may also include such features as: a spin-echo (SE) sequence; two
fast spin-
echo (FSE) double echo sequences; and fast stimulated inversion recovery
(FSTIR) or any of
a variety of sequences approved for safe use on the imager. Contrast agents
are types of
drugs which may be administered to the subject. If given, contrast agents
typically distribute
in various compartments of the body over time and provide some degree of
enhanced image
for interpretation by the user. In addition to the above, pre- and post-
contrast sequence data
sets were acquired. In other embodiments, a Tl, T2, proton density, and four
echo sequences
were acquired. Any acceptable data acquisition method, sequences and
combinations thereof,
can be used to collect the data according to the present invention. Thus, by
using multiple
sequences, multivariate image data can be obtained. Each pixel can be
considered a sample
and by using different sequences to image the same physical location, each
sequence
produces a new measurement for the sample.
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Each data element under consideration has one or more properties which
describe a corresponding portion of the object which the data element
represents. Each of
these properties has a numerical value. For example, if the image which has
been acquired is
an MRI image, then the properties of each data element may include such
features as the
longitudinal relaxation factor, TI, or the transverse relaxation factor, T2,
weighted T1 or T2
images, the proton density space, or other parameters which are normally
measured in an
MRI, as is known in the art. Therefore, each of the data elements known has
the numerical
value which is related to each of the properties that provides a description
of the data
element. Each data element will thus be described by several different
numbers, one number
for each of the properties stored. The data is thus multivariate. The
numerical values may be
thought of as defining the position of a data element in mufti-dimensional
space and
reflecting the magnetic resonance properties of the tissue corresponding to
that location.
Namely, each one of the parameters represents one of the dimensions for the
location of the
object in a Euclidean geometry field. If two properties of an object are
stored for each data
element, then the field becomes a two-dimensional Euclidean plane. If three
parameters are
stored, then the data element can be considered as being at a location in a
three-dimensional
Euclidean field. Similarly, if four physical parameters are represented, then
the object may be
considered as being at a location in a four-dimensional Euclidean field. Each
data element,
therefore, has a location within the mufti-dimensional Euclidean field.
In Figure 1, an object to be examined, in this case a patient's body 20, is
S110W11. A slice 26 of the body 20 under examination is scanned and the data
collected. The
data are collected, organized and stored in a signal processing module 18
under control of a
computer 14. A display 15 may display the data as they are collected and
stored. It may also
provide an interface for the user to interact with and control the system. A
power supply 16
provides power for the system.
The current known clinical standard for locating tumor tissue with MRI
involves having an experienced radiologist interpret the images for suspected
lesions.
Radiologists are skilled in detecting anatomic abnormalities and in
formulating differential
diagnoses to explain their findings. Unfortunately, only a small fraction of
the wealth of
information generated by magnetic resonance is routinely available because the
human visual
system is unable to correlate the complexity and volume of data. The specific
problem is that
radiologists try to answer clinical questions precisely regarding the location
of certain tissues,
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but seldom can they extract enough information visually from the images to
make a specific
diagnosis because the tissues are very complex and therefore difficult to
fully segment in the
image provided. This problem is compounded for MRI which produces many
different types
of images during a single imaging session.
To use all of the information created by an MRI examination, radiologists have
to simultaneously view several images created with different MR scanner
settings and
understand the simultaneous complex relationships among millions of data. The
unassisted
human visual system is not capable of seeing, let alone processing, all of the
information.
Consequently, much of the information generated by a conventional MRI study is
wasted.
Consequently, there is a great need to efficiently utilize more of the
existing MR information
to more accurately segment the various tissues and thereby improve the
confidence of
conclusions drawn from the interpretations of medical images. Because a proper
determination of the location and the extent of a tumor (a process called
staging) will
determine the course of treatment and may impact the likelihood of recovery,
accurate staging
I 5 is important for proper patient management.
To assist the radiologist in making diagnostic decisions and to reduce the
time
and expense associated with the analysis of magnetic resonance (MR) data,
computerized
MR-based tissue segmentation methods have been developed, where segmentation
refers to
the specific application of pattern recognition technology in the analysis of
images, some of
which are described in the three patents incorporated by reference. The
purpose of the prior
art MR-based tissue segmentation methods is to divide the pixels within an MR
image into
different tissue types. The success of MR-based segmentation methods lies in
the ability of
the computer to quickly and correctly correlate all of the digital information
provided by
MRI.
Attempts at supervised segmentation methods have been made in the analysis
of MRI images, but with limited success. Training samples are typically
obtained through a
manual labeling of a few pixels or contiguous regions in the image set for
each tissue of
interest by a qualified observer. Multiple tissues or classes are modeled and,
for a given test
sample, a value is calculated for each modeled class indicating the similarity
of the test
sample to the class in question. The test sample is then assigned to the
modeled class to
which it is deemed most similar. An obvious problem with this approach occurs
if all classes
within the image set have not been modeled. If a given pixel belongs to an
unmodeled class,
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it is falsely assigned to one of the modeled classes utilizing current
supervised segmentation
techniques.
The present invention provides an MRI-based supervised segmentation
method that allows the automated and accurate identification of tissues of
interest, such as
tumor, without the requirement of modeling all tissues within the image set.
One approach to classification of data according to the invention is shown in
Figure 2. As shown in Figure 2, data 30 are acquired. The data can be acquired
using any
acceptable technique and protocol. As previously stated, the data can be
collected using the
prior art MRI system as shown in Figure 1. Alternatively, other systems for
acquiring and
storing the data may be used. For example, NMR or other medical imaging
techniques may be
used. The invention may also be used in the other fields previously described.
Thus, the
invention is independent of the particular acquisition protocol and the
equipment used to
acquire and store the data. Once the data has been stored, as shown in block
30, it is now ready
to be treated according to principles of the present invention.
In order to proceed to the next step, a user, usually a medical technician or
physician, obtains an image from the data. On the image, the user selects a
region of interest
for which further examination is desired, step 38. This region of interest may
be designated
on a screen using a computer mouse, forming a box around a target site, that
includes a
known tumor site, or some other technique by which a user may designate a
region of
interest. Normally, a user will indicate a region of interest that includes
two or more types of
tissue. It is therefore necessary to divide the data elements into classes
that represent the
types of tissue in the region of interest.
Automatic clustering of tissues within the region of interest is carried out
as
shown in step 40 to divide the data elements into classes reflecting the types
of tissues. If the
region of interest is quite small and specific, there may be only two or three
types of tissues
within the region of interest. Alternatively, there may be five or more types
of tissue within
the region of interest. The automatic clustering provides a segmentation of
the different types
of tissues that are found within the region of interest which has been
designated.
After the automatic clustering is performed, the next step 42, guided tissue
selection is carried out. The user performs a guided tissue selection as will
now be described
according to the present invention. After the clustering of tissues is
performed, the user
selects one or more clusters which represent a type of tissue which is of
particular interest for


CA 02391289 2002-05-10
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further study. In standard use of the present invention, the type of tissue
being selected will
normally be a tumor which is suspected of being malignant. In some
applications, the tumor
may have previously been confirmed as a malignant tumor and it is desirable to
know the
exact shape of the tumor and whether the cancer has spread outside the initial
tumor
boundaries. It is also desirable to know whether the cancer is present in
other portions of the
body. For each selected cluster, an automatic classification threshold is
calculated utilizing
information contained within each corresponding set of training samples.
In step 44, the specific tissue segmentation is performed. The automatic
classification threshold has been applied in step 44 and now it is desired to
provide an
indication of those data elements in the test set which are sufficiently
similar to the training
set. In the case of image data, the samples or pixels which are deemed
sufficiently similar to
the training set at the current classification threshold are considered to be
within the same
class. The final segmented image is then displayed, step 34.
Steps 42 and 44 are particularly relevant to the invention and will be
described
in more detail in Figures 3 and 4, concerning the establishment of an
automatic classification
threshold, the dynamic modification of this classification threshold, as well
as the creation of
an image using similarity data, and thus will be discussed in greater detail.
Figure 2, providing an overview of the invention has now been described.
Some of the specific details for each of the steps will be provided. Step 40,
the automatic
clustering will be described in more detail as follows.
The tissue in each volume element (voxel) of the subject is represented as
pixel data in the image. The display characteristics of a single pixel in the
image thus
represents the characteristics of a corresponding voxel imaged by the MRI
equipment.
A data element has a numerical value in each of two, three, or four or more
properties. The numerical values place each data element at a location in a
Euclidean
geometry composed of two, three, four or more dimensions, one dimension being
used for
each numerical value. The location of the data element can thus be known in a
multivariate
space. Data elements that are in the same general location in multivariate
space represent
voxels whose contents have properties very similar to each other. Namely, for
two highly
similar or identical tissues which occupy separate voxels, all the
corresponding pixel data
elements representing those voxels will have highly similar or identical
numerical scores in
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the multivariate space and thus will be deemed highly similar to each other
when measured in
Euclidean geometry.
The goal of cluster analysis is to uncover any intrinsic structure within a
set of
samples based on measurements made on these samples. Samples are grouped
together into
clusters based on their proximity in multivariate measurement space, where
samples within a
given cluster exhibit a high degree of similarity. In MRI, each different
cluster typically
represents different tissuetypes, which thus have different signal intensity
characteristics. In
one embodiment, the fuzzy C-means algorithm is implemented. The key concept of
the fuzzy
C-means algorithm is that each sample exhibits varying degrees of membership
in each of the
clusters. A membership value close to one indicates a high level of similarity
between the
sample and a cluster, and a value near zero indicates little similarity
between the sample and
the cluster in question. The fuzzy C-means algorithm has proven valuable in
the analysis of
MRI data due to its ability to explicitly model partial voluming effects.
Mathematically, the fuzzy C-means algorithm can be summarized as follows.
I S Data collected during the course of an MRI study can be organized into a
four-dimensional
array, F,x,X,~X,. , where I designates the number of rows within the array, .7
the number of
columns, K the number of MRI data sequences, and L the number of slices within
the study.
The intensity value for a particular array element, f;;k, , can be accessed by
specifying a row-
column-sequence-slice address, where i = 1,...,1 is an index indicating the
row position,,] =
I,...,J is an index indicating the column position, k = 1,...,K is an index
for the MRI data
sequence, and 1 = 1,...,L is an index for slice number. Elements of this four-
dimensional
feature array can be extracted to form other useful data structures. For a
given pixel located in
row i, column j and slice number l, a sample vector is composed of the values
for the K
measured sequences:
fKX~ _ ~f,;n, f.;~r,..., f,;K,~T . A collection of N sample vectors organized
by rows forms a
sample set designated by the matrix, FNx,; . For a set of N sample vectors,
F~X~, containing C'
clusters, the fuzzy C-means algorithm is based on minimization of the
following objective
function, J9, with respect to U~,t,~, a fuzzy C-partition of the data set, and
to V,~-~-~, a set of C'
prototypes:
N ('
\1 '/ 1'r ~7 '_7'l
Jq~~('-zN~~Kx('~ ~~~uc'n~l ~ ~Vc~fn~
rr=1 c=1
where f" is the nth K-dimensional sample vector, v~ is the centroid of the cth
cluster, u~." is the
degree of membership of fn in the cth cluster, q is a real number greater than
1, and d(v~.,f") is
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the distance between f» and v~. The weighting exponent, q, controls the
fuzziness of the
resulting clusters. The fuzzy partition matrix, Uc,t,~, contains the
membership value of each
sample for each cluster. The C cluster centers are collected in the cluster
center matrix, VKXc
_ {v~, v2,..., vc}. The distance between sample fn and cluster center v~ is
computed as
S dOc~f»~=~~ff-v~~T~f»-v~.~]°.s.
An optimal fuzzy clustering of the sample set, FNxK, is defined as the fuzzy
partition matrix-fuzzy cluster centers pair, (UcxN, VKXc), that locally
minimizes the fuzzy
objective function, J9. Optimization is achieved through an iteration of the
following steps:
(1) Initialize the fuzzy partition matrix, U, using a random number
generator such that
c.
u~." =1
c=1
(2) Compute the fuzzy centroid v~ for c = 1,..., C using
N
~ua» ~y f»
v = »=1
c' N , '
\uc» ly
»--1
(3) Compute an updated membership matrix, U, via
_1
1 w'
d2wa~f»~
uc» = 1
c. 1 v_1
d wc~~f,r~
(4) Repeat steps (2) and (3) until the reduction in Jg between two
successive iterations is less than a defined threshold or the number of
iterations exceeds the accepted limit.
A difficulty in the practical implementation of clustering involves
determining
the number of distinct groups or tissue types within the selected region of
interest. As the
results of clustering and, therefore, classification are dependent on the
number of clusters
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employed, it is imperative that an accurate, automated method be implemented
to assist the
user in making this selection. In one embodiment, the Xie-Beni fuzzy validity
criterion has
been implemented to automatically select the number of clusters. The Xie-Beni
fuzzy
validity criterion identifies overall compact and separate fuzzy C-partitions
without
assumptions on the number of groups inherent in the data. For a set of N
sample vectors,
FN~~-, and a given number of clusters, C, the Xie-Beni index is calculated as
follows:
~~Ow,O~d~wa~f,~~
s = ~~=t ~=t
N(dmin
where d",;" is the minimum distance between cluster centroids. The numerator
of the Xie-
Beni index is a measure of cluster compactness, while the denominator is
indicative of the
degree of separation between clusters. A smaller Xie-Beni index indicates a
partition in
which all the clusters are overall compact and separate. The optimal number of
clusters is
determined by calculating the Xie-Beni index for a range of cluster numbers
and selecting the
value of C for which S is a minimum. A group of clusters will thus be
represented as groups
of pixels, all clustered together. Usually, each cluster will be separated
from each other
cluster by some distance, based on the differences of the respective tissue
type represented by
each respective cluster of pixels.
A cluster of interest will thereafter be selected for further study.
The Xie-Beni Fuzzy Validity Criterion is well known in the art and has been
published, see for example the article by X.L. Xie and G. Beni in IEEE
Trun.suction.v orr
Pattern Ar~alysis~ and Machine Intelligence, Volume 13, page 841-847 (1991).
As shown in Figure 3, the user then performs a guided tissue selection in step
42 as will now be described in more detail according to the present invention.
After the
clustering of tissues is performed, the user selects one or more clusters
representing one or
more tissue types which are of particular interest for further study. In
standard use of the
present invention, the cluster selected will normally be a tumor. In some
patients, the lesion
may have previously been confirmed as tumor and it is desirable to know the
exact shape of
the tumor and whether the cancer has spread outside the initial tumor
boundaries. It is also
desirable to know whether cancer is present in other portions of the body.
According to the present invention, selection made of a class of tissue 50
that
has been classified by the clustering in the prior step 40 as the specific
tissue of which further
examination is desired. In the present example, it will be assumed that a
tumor is selected in
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step 50. After the specific tissue is selected in step 50, a training set of
individual data
elements is created in step 52 which is representative of this selected type
of tissue for which
further search and study is desired.
In designating a training set, the goal is to incorporate data elements which
are
representative of the tissue of interest, while excluding data elements that
represent other
tissues. The training set will then be used to determine which data elements
within and
outside the region of interest are similar to in the training set.
In some embodiments, a data element in the stored data has a one-to-one
correspondence to pixels in the display. In other embodiments, a data element
may be
represented by multiple pixels, or vice-versa, depending on the resolution of
each, the type of
display, and other factors.
In one embodiment, the set of training samples is selected from the full set
of
cluster samples using the fuzzy partition matrix, U~XN, obtained via the fuzzy
C-means
clustering algorithm. First, the cluster samples having a maximum membership
value for the
selected cluster, c, are identified. Next, for each sample within this subset,
the percentage
difference between the largest and second largest fuzzy membership value is
calculated. Only
if this difference exceeds a specified percentage level (e.g., 90%) is the
cluster sample
incorporated within the training set. This training sample selection procedure
ensures that those
cluster samples which are representative of the tissue of interest (e.g.,
those close to the cluster
center, v~) are included in the training set, while outliers are not.
Each of the data elements within the region of interest has been placed in the
particular class to which they most closely belong in the prior step 40. One
of the classes is
selected to create the training set. After the class is selected from which
the training set will
be created, the number of data elements in the training set is refined to
represent only those
core elements which most closely represent the core properties of this class.
For example, all
of those data elements having a low fuzzy membership value for the selected
cluster are
removed from the training set. These may be referred to as outliers. For
example, a data
element is placed within a particular cluster when its fuzzy membership value
for that cluster
is higher than for any other clusters within the region of interest. Thus, the
data element is
defined as being more closely associated with that cluster than any other
cluster within the
region of interest. However, once a training set is going to be created for a
particular cluster,
a threshold is established for data elements which are within the cluster to
be included within


CA 02391289 2002-05-10
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the training set. If the fuzzy membership value for the particular data
element falls below the
acceptable threshold, then it is not included within the training set, even
though it is still
considered a member of the cluster. For example, consider the case where there
are three
clusters and the sum of the three fuzzy membership values for each pixel
equals 1Ø The
fuzzy membership value for a given cluster ranges from 0 to 1. Thus, if for a
given data
element one of the fuzzy membership values is 0.9 or 0.95 then this indicates
the other two
fuzzy membership values for that particular data element are quite low and
that data element
is a strong member of the class. On the other hand, if all the fuzzy
membership values are
approximately equal, then classification of that particular data element in
one class or another
is very close and using it as a member of the training set is not appropriate.
Thus, all data
elements whose fuzzy membership value for the selected cluster fall below the
threshold are
stripped away from the class and are not placed into the training set. In one
example, the
threshold may be 0.7 or, alternatively, 0.8. Thus, only those data elements
having a fuzzy
membership value higher than the threshold, for example in the range of 0.7-
0.8 or higher
will be included in the training set. The training set is thus created having
a group of data
elements which have characteristics strongly representative of the selected
class. Those data
elements which may be more closely associated with that class than any other
class, but are
not strong members of the class, are removed and do not become members of the
training set.
After the training set is created, as shown in Figure 3, step 52, an automatic
threshold value is created step 53 for the training set that will be distinct
for that particular
training set. The automatic threshold of step 53 is created as follows. The
distance between
each member of the training set, and every other member of the training set is
calculated. As
described elsewhere herein, each data element may be considered as being at a
location in a
mufti-dimensional space. Thus, using Euclidean geometry the distance between
data
elements can be calculated. Since the location of a data element within the
Euclidean field is
directly related to its properties, the more closely the training elements are
to each other the
more similar are the physical properties of the tissue that they represent.
Therefore, a
numerical value representative of the distance between data elements is a
reliable
determination of the similarity of the characteristics of the tissues which
the data elements
represent. If the distance between them is small, namely at or near zero, then
the tissues are
determined very similar to each other. On the other hand, if their distance is
great, then the
properties of the tissues that the data elements represent are not similar to
each other.
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The maximum distance that any member of the training set is from its nearest
neighbor in the training set is established as the automatic threshold.
Namely, in step 53, the
distance between each training set data element and the data element nearest
to it within the
training set is determined. Then, that distance which is the greatest for the
nearest neighbor
pair of data elements is selected as the custom threshold distance.
As will be appreciated, this automatic threshold is created by the steps of
the
invention and will be different for every single training set which is
created. Accordingly, it
is termed an automatic threshold because for every single data collection the
calculation is
automatically done and the value of the threshold will be different. The
concept is that the
value of the threshold is based on the similarity of the data elements within
the training set to
each other. If all members of the training set are very similar to each other,
then the threshold
will be correspondingly low because the greatest distance between any two
members will be
low. On the other hand, if the training set is composed of data elements which
are more
different from each other, then the automatic threshold will be higher. Thus,
the automatic
threshold, as calculated, provides a determination of the relationship of the
data elements to
each other within the training set. It is a custom number calculated for each
tissue being
studied in each patient and therefore captures the individual characteristics
of the patient's
tissues. This same relationship will then be used to determine whether data
elements in the
same patient but not within the training set should also be included within
the same class as
the training set.
This automatic threshold number will be stored and saved for each patient and
each tissue type for which a training set is created for a patient. If the
patient receives
another MRI, months or even years later, all this data will be available. The
custom threshold
number for a given training set in this patient may be useful as a comparison
standard for any
new measurements taken months or years later. It may also be used to calibrate
and then
normalize data taken by the same MRI machine years later, or by a different
MRI machine.
It is known that the data collection characteristics vary from machine to
machine for the many MR, NMR, CT, PET, and other imaging and non-imaging
sensors now
in use. Further, the characteristics of one sensor may change over time as the
parts age,
operating temperature changes, or other factors affecting a machine.
Automatically
calculating a custom threshold for each set of data that is used as a training
set provides a
self calibration for each machine and each tissue sample for each patient. The
subsequent
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classification of tissue thus has a more reliable standard than was possible
in the prior art. In
addition, by saving the data and the custom threshold, they can be used at a
later time to
compare to later tests of the same patient to assess and quantify improvements
or changes
over the treatment time. A later collected data set may, for example, have its
own custom
threshold created and this can be compared to the prior custom threshold and
the prior custom
threshold can be used on the new data to see if more accurate results can be
obtained or to see
more clearly the changes over time.
As shown in Figure 3, once the automatic threshold has been created, the next
step 54 is to determine whether or not additional elements outside of the
region of interest
should be included within the same class step 54. This is accomplished by
comparing the
distance between each member of the training set with each data element in the
entire array,
step 54. If the distance between a test data element and any one member of the
training set is
less than the automatic threshold, then that data element is included as a
member of the
training set class, step 58.
A comparison is carried out between each member of the training set and each
data element outside of the training set. Preferably, all the data elements
which compose the
entire original data in step 30 are compared to determine whether or not any
of the selected
tissue is located outside of the region of interest, and in particular,
whether it is located in
other portions of the body.
Any of known acceptable techniques may be used for comparing the training
set of data elements to the test set of data elements which represent the
object under
consideration. One particular acceptable comparison technique will be
summarized, after
which will be described in more detail even though other techniques may be
used.
The numerical values associated with each member of the training set are
compared to the numerical values associated with every other data element of
the object
under investigation. Since the numerical values of the data element are
related to the physical
properties of the object under investigation for each data element, its
location in the multi-
dimensional Euclidean field is related to the physical properties of the
object. In the
comparison of the training set to the test set, the closer that two data
elements are to each
other within the multi-dimensional Euclidean field, the more similar they are.
Thus, the
distance between the two data elements with respect to each other becomes an
accurate and
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reliable measure of the similarity of the properties of the object represented
by the data
elements.
The distance from a data element in the training set and a test sample data
element can be represented as a numerical value which provides a similarity
for the test
sample data element. The numerical value of this similarity represents the
similarity between
the test sample and the training set. The smaller the distance, the more
similar the data
elements are to each other. Thus, a distance of 0 indicates the data elements
are so similar to
each other than they may be considered identical and members of the same
class. Higher
distances indicate less similarity. Depending on the scaling used, the
numerical distance
value may be a single digit number, such as a number one through ten.
Alternatively, it may
have many digits such as a seven- to ten-digit number. For some embodiments,
the distance
number is expected to be sufficiently large for nearly all test samples in the
data set, that the
logarithmic value may be taken after the distance value is obtained in order
to normalize the
distance values. The absolute distance value is not so important as the
relative distance value
compared to the distance for other data elements in the test set and also the
distance of a
training data element when compared to other elements in the training data
set.
The above concepts will now be described from a mathematical model for an
example of how the invention may be carried out. In this example, data
collected during the
course of an MRI study is organized into a four-dimensional array, F,x,xKx,. ,
where I designates
the number of rows within the array, J the number of columns, K the number of
MRI data
sequences, and L the number of slices within the study. The K sequences are
the features
utilized in tissue segmentation. The intensity value for a particular array
element, ,f,~~, , can be
accessed by specifying a row-column-sequence-slice address, where i = 1,...,1
is an index
indicating the row position, j = 1,...,J is an index indicating the column
position, k = 1,...,K is
an index for the MRI data sequence, and l = 1,...,L is an index for slice
number. Each data
element in the array can be thought of as occupying a location in a 2-, 3-, 4-
, 5- or other multi-
dimensional field. Such data element is sometimes termed a voxel. For a 2-
dimensional screen
image, each display element is usually referred to as a pixel.
Elements of this four-dimensional feature array can be extracted to form other
useful data structures. For a given voxel located in row i, column j and slice
number l, a
sample is composed of the values for the K sequences:
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f T
fxm = ~.fiv~.f;v~...,.fi;xn
A collection of N voxel samples organized by rows forms a sample set
designated by the matrix, FNxK
An automatic classification threshold has been established using information
contained within the training set samples in step 42 as previously described.
This automatic
classification threshold sets the initial cutoff level for determining which
test samples are
sufficiently similar to the training set to be considered a member of the
class of interest. In
one embodiment, the "near enough a neighbor" (NEN) criterion is utilized to
establish a
classification threshold. The NEN criterion determines a classification
threshold based on the
maximum of the nearest neighbor distances within the training set samples. The
nearest
neighbor distance values for the test samples are compared to this automatic
classification
threshold to determine which of these test samples are sufficiently similar to
the training set
to be considered a member of the class of interest.
The similarity values will be calculated and displayed, as shown in Figures 4
and 6A, however, in some embodiments it is preferred to perform some prior
clustering and
selection as will now be explained. For each voxel, segmentation is initiated
by calculating a
similarity value for each specified class. For a given class, an output of
segmentation is a
three-dimensional similarity array, D,x,X,, , containing the similarity value
at each voxel
position (i,j,l).
In one implementation of MR segmentation, the user designates a set of voxel
samples, FN~x , representing a single tissue class. Having identified these
training samples.
supervised segmentation is performed utilizing the nearest neighbor method.
The classical
single nearest neighbor method can be used at this stage, which is a
nonparametric decision
rule which classifies an unknown test sample as belonging to the same class as
the nearest
sample point in the training set, as described in a publication by Gose et al.
in 1996. The
degree of similarity between a test sample, Rest , and a training sample, f" ,
can be defined in
terms of their Euclidean distance in K-dimensional feature space
~~f test ~ f,i ) _ ~ \J test.k - J nk
k=1
The distance from the test sample to each training sample in the training set
is
measured, and the minimum of these distances is selected. Namely, the distance
value for the
test sample is based on how close the test sample is to the nearest one of the
samples in the


WO 01/39123 CA 02391289 2002-05-10 pCT/US00/32204
training set. An output of nearest neighbor segmentation is a three-
dimensional similarity
array, D,x,~,, , containing the minimum distance at each voxel position
(i,j,l).
Figures SA and SB illustrate the advantageous results which can be obtained
by using the automatic threshold according to the present invention. Figure SA
illustrates an
MRI of the subject which has been reviewed by a radiologist for suspected
tumor locations.
The radiologist identified regions 60 and 62, both encircled, as likely tumor
sites. Region 62
corresponds to a mass in the nasopharynx whereas region 60 corresponds to
nodular masses
of variable size in the fatty tissues deep to the left cheek. Using the
concepts of the present
invention, the mass within the nasopharynx in region 62 was selected as a
region of interest.
Automatic clustering was carried out using the techniques as described herein.
Following
this, the mass in the nasopharynx within circle 62 is identified as the tissue
from which a
training set should be created. Accordingly, a training set was created from
the class of data
elements that represent the large mass 62 in the nasopharynx. After the
training set was
created, an automatic threshold was generated by comparing members of the
training set to
each other and selecting as a threshold that value which was the maximum of
the nearest
neighbor distances as previously described herein. Once the automatic
threshold was
obtained, then all data elements in the MR image were compared to the training
set to
determine those that were within the threshold distance and thus should be
classified in the
same class of tissue as that found within region 62 in the nasopharynx. A
binary
segmentation result was obtained by applying the threshold, such that pixels
whose distance
values were less than or equal to the threshold were designated as members of
the training set
class. After the classification of all data elements in the entire MR image
was completed, the
original unclassified MR image was overlaid with a display showing in black
all pixels which
deemed similar to the training set. The resulting image is shown in Figure SB.
As can been seen in Figure SB, the regions 60 and 62 are shown completely in
black, illustrating that they both belong to the same class of tissue. This
makes clear the
radiologist's initial interpretation that these two tissues likely were
cancerous tissues of the
same type. Of some interest, the enhanced image also showed an additional
region 64 which
had previously not been detected by the radiologist. This additional region 64
was also
overlaid in black pixels, indicating that it is likely the same type of tissue
as the regions 60
and 62 and thus, is a probable, additional site of the spreading cancer
tissue, in this case
located in the left sinus cavity. This confirms, therefore, that there are two
remote lesion
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sites, 60 and 64, which are highly similar to the reference mass 62 and thus
indicate a high
likelihood of metastases of the cancer.
The image provided according to the present invention has a number of
advantages. First, as can be seen by comparing Figures SA and SB, the specific
sites of the
tumor can more clearly be seen in Figure SB. Thus, the boundaries and exact
location of the
tissues of interest are more exactly known by viewing Figure SB. In the event
surgery, or
some other invasive treatment is desired, having the MR image of Figure SB
becomes
extremely useful to more precisely locate the tissues which share the same
characteristics. In
addition, by definitely locating another tissue in the MR image as being of
the same type, the
spread of the tissue can more accurately determined. Further, within the
portion of the body
imaged, confirmation that the cancer has not spread to other locations can
also be confirmed.
Only three sites were highlighted in Figure SB as being the same tissue and
thus, the
physician has a high degree of confidence that no other tissues are of the
same type and that
the cancer is confirmed to three locations. Given the general difficulty of
interpreting and
reading various medical images, the advantage of the present invention of
highlighting
specific tissues which share the same property has a number of advantages in
medical
diagnosis.
Figure 4 illustrates further steps that can be carried out according to
principles
of the present invention as part of step 44 of Figure 2. Figure 4 shows the
steps for creating
similarity data and then displaying the similarity data. The data are
acquired, step 30, as in
the prior Figure 2 and the other steps carried out to reach step 44. The next
step 32 follows
the creation of a training set of the same type as that of Figure 3.
Similarly, the automatic
thresholding step is carried out in order to determine a threshold value.
Following this, the
similarity values are determined from each data element in the test sample,
step 32.
After the distance to each data element outside the training set has been
determined, step 32 is carried out in which a color is assigned to each pixel
based on its
distance from the training set. According to this embodiment, all pixels in
the training set are
assigned to a particular color. If the distance between any data element in
the training set and
test data element is less than the automatic threshold amount, it is assigned
to the same color
as the training set. If the distance of the data element is just slightly
greater than the
threshold distance, then it is assigned a color which is just slightly
different from the color of
the training set. The greater the distance between the test element and the
training set, the
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WO 01/39123 CA 02391289 2002-05-10 pCT/US00/32204
greater the difference in color. Accordingly, a color will be assigned based
on the similarity
of the test sample to the training set. The color changes representing the
different degrees of
similarity may be shades of a single color or a palate of distinct colors or a
combination of the
two color display methods.
According to one embodiment of the present invention, the color selectin for
display of similarity is based on the color spectrum for visible light. As is
known, red has the
lowest frequency visible to the unaided human eye. Progressing along the color
spectrum of
light from red, the next color encountered is orange, followed by yellow.
Continuing to
progress along the color spectrum for visible light, the next colors
encountered are green,
greenish blue, blue, violet.
In one embodiment, the class to which the training set belongs is assigned the
color red within the visible color spectrum of light. All test data elements
which are within
this class are also shown in red. All test data elements not within the same
class as the
training set are assigned to a color whose frequency is proportional to the
distance that the
particular test data element is from the training set. For a test data element
which is quite
close, it is assigned to a very similar light spectrum to that of red, namely,
an orange-red
color. For those spaced slightly further from the class of the training set, a
color is assigned
in the color spectrum which is proportionally farther from red, such as orange-
yellow or
yellow. This is performed for all members of the training set. These colors
are then overlaid
(in either opaque or a degree of transparent color or in some pattern such as
cross-hatched or
stippled) on top of the MR image which, in normal instruments, is a grayscale
image that will
appear in different shades of black and white. By overlaying a color image
whose frequency
spectrum varies proportional to the similarity of the tissue under study, the
radiologist can
very quickly and easily see the exact location of identical type tissues and,
in addition, can
see similar type tissues which appear to be related to the tissue under
investigation.
A binary image may also be created, step 36 as shown in Figure 4. The binary
image
may be a gray scale image, of the type similar to that shown in Figures SA and
SB or,
alternatively, it may be a two-color image, such as a gray scale image in
combination with
one other selected color which has strong contrast against gray scale, such as
orange, yellow
or red. In a binary image, pixels are grouped into two classes, those that are
termed "on''
and those that are termed as "off." The "on" pixels all have a predetermined
intensity and/or
color that is the same for all pixels in the set. The "off ' pixels retain
their original display
23


WO 01/39123 CA 02391289 2002-05-10 pCT/US00/32204
characteristics. The "on" pixels are overlaid on the MR image to provide a
binary image for
the user.
The selection of pixels to be "on" or "off' in the binary image can be done
using the
same classification system that has just been described with respect to the
custom threshold.
After the custom threshold is obtain and applied to the image, those pixels
within the same
class as the training set are turned "on" and the remaining pixels are left
off. Alternatively, a
more strict standard may be used, with a higher threshold than the custom
threshold so as to
require that the pixels be very similar to each other to be turned on in the
binary image. As a
further alternative, the binary image may be created using as a standard, the
using the fuzzy
clustering technique as previously described.
Thus, the binary image will show two colors, all tissue within the same class
of the training set being in a first color and all other tissue being in a
second color, with the
potential that the second color may be a single solid color which has contrast
with the first
color or the gray scale image. This type of display is shown in Figure 6B as
will be
explained later herein. Alternatively, the binary image may be created using a
threshold
value. The threshold value may be the custom, automatic threshold value as
previously
described or, alternatively it may be a dynamic threshold value as explained
with respect to
Figures 7A and 7B. The threshold value may, therefore be a different number
than previously
used for the maximum similarity, particularly if a dynamic threshold is used.
When the
threshold technique is used, the similarity of values, having been calculated
in step 32 are
compared to the threshold value. Those pixels which are within the threshold
value are
shown as the first color, while those pixels which are not within the
threshold are shown in a
second color, or in a gray scale. Accordingly, the physician is provided a
binary display of
the data in two colors to more quickly and easily highlight the exact regions
of the tissue
which have an exact match within the threshold of interest.
Providing to the physician, in a side-by-side format, the original MR image
and then, the overlaid version of the same MR image according to the present
invention has
significant advantages. The physician viewing the original MR image is able to
locate
specific regions of tissue for further investigation and note those areas for
which particular
study is desired. Then, the same MR image is overlaid with the pixels modified
as described
in the present invention. This can be displayed side-by-side with the
unaltered image. The
24


WO 01/39123 CA 02391289 2002-05-to pCT~S00/32204
physician can quickly and easily see all changes which have been made by the
processing
steps of the present invention. Tl~e changes will therefore more particularly
be highlighted to
the physician with the realization that these are based on a comparison of the
tissues of
particular interest. The changes which are made between the original MR image
and the
modified MR image therefore provide additional information to the physician in
understanding the type of tissue at each location, and the size and extent of
the tissue growth
at each particular location. This side-by-side pattern is shown in Figures SA
and SB and also
Figures 6A and 6B.
In the embodiment shown in Figures 6A and 6B, the side-by-side comparison
is between a color similarity image and a binary similarity image. Again,
providing the
physician a color spectrum similarity image adjacent a binary image provides
significant
advantages in understanding the tissue located at each site, the tissue growth
patterns and the
extent of any tumors which may have spread. These also provide significant
advantages in
permitting the physician to ignore false positives which may occur in the
original image, or
possibly in the modified image.
Figures 6A and 6B illustrate an MR image which has been overlaid with a
color change of those pixels which represent the data elements based on their
distance from
the training set, corresponding to a tumor site, as carried out in steps 34
and 36 of Figure 4.
Those pixels which are the most identical to the training set are colored red
as can clearly be
seen by region 72 in Figure 6A. Those regions which are quite similar to the
training set, but
not sufficiently similar to be within the same class, have a slight orange
color, as can be seen
by reviewing regions 74 of Figure 6A. Those tissues which are the next most
similar have a
yellow color, regions 76 of the tissue in Figure 6A. The regions next most
similar have a
yellowish green, followed by a green color. The tissues least similar have a
dark blue,
approaching a violet in color.
Segmentation results are displayed to the user in the form of similarity
images.
For a slice l, the corresponding similarity image, D,x,,, , is displayed using
a specified color
map. Figure 6A is one example of a color display and having the presentation
of
segmentation results using the similarity image method and binary thresholding
for an MR
animal study according to the invention. T1-weighted, T2-weighted and STIR
(short tau
inversion recovery) sequences were acquired and utilized in segmentation. In
this example,
the user designated a set of tumor pixels as the region of interest and a
nearest neighbor


CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
distance value was calculated for each of the remaining pixels in the image
set. In displaying
the similarity image, a color map was used. All pixels in the training set
appear red.
According to the invention, pixels with a relatively small distance values
(high similarity
values) for the selected class appear the same color as the training set, in
this case red, while
pixels with relatively large distance values (small similarity values) appear
dark blue.
Viewing Figure 6A, four core regions having red at a central portion thereof
can easily be seen. Each of these regions has a yellow fringe around the edges
indicating that
these very similar tissues are located at the edges, even though they are not
so similar as to be
within the red class. The remainder of the image is shown in blue. Namely, it
is clear that all
other types of tissue are distinctly different from those tissues which have
been indicated as
belonging to the class of interest, in this case tumor. Since all of the
portions of the MR
image have been overlaid with the blue, the physician has a very high
confidence that the
tumor is not located in other regions beyond those which have been highlighted
in red. The
ease of reading the MR image is greatly improved using the similarity of color
image in the
present invention.
Figure 6B is the same MR image of Figure 6A, however, a grayscale image is
overlaid with a single color indicating only those pixels which belong to the
same class as the
training set. In Figure 6B, a threshold was applied in step 36 and all pixels
that correspond to
data elements within the threshold distance were assigned a color of yellow,
regions 73, 75,
77 and 79. All other pixels not within the similarity threshold distance
retained their original
grayscale color of the original MR image. Thus, Figure 6B appears more as a
binary image
in which the tissue of interest is in one color and all other tissues are in a
grayscale pattern. It
thus has a binary image with only those pixels which fall within the threshold
being
highlighted.
The advantages of using similarity display of data can be seen by comparing
Figures 6A and 6B. In Figure 6A, much larger regions are illuminated with
slight variations
in color as to quickly draw the radiologist's attention to those tissues of
interest. Since the
center of most larger tumors is often necrotic, namely dead tissue which was
formerly living
tumor tissue, it will have characteristics somewhat similar to the class of
interest, but will be
sufficiently different that it does not belong to the same class as the
otherwise living tumor
tissue. In the binary image, such tissue does not show as belonging to the
same class, with
the result that the physician may not fully appreciate the scope of the tumor.
However, in the
26


CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
Figure 6A image, a larger amount of tissue is highlighted for more easy
recognition to
understand the scope of the tumor and, permit the understanding of the
necrotic tissue within
the center of the tumor region. Further, Figure 6A, showing that all other
portions of the MR
image are blue, indicates that there is no similar tumor issue anywhere else
in the array.
Figure 6B, in which the remainder of the MR image is on a grayscale, requires
additional
consideration and further study by the radiologist in order to confirm whether
or not
additional tumors may be present.
As shown in Figure 6B, in generating the binary thresholded image, pixels with
distance values less than or equal to the designated threshold are highlighted
in yellow on the
T1-weighted MR image. Regions suspicious for tumor are readily apparent in the
similarity
image of Figure 6A, via the pixels' elevated brightness levels and different
colors. In contrast,
similarity information is not as easy to understand in the binary image
display of Figure 6B
through the application of a subjective hard threshold. As an example, in
Figure 6B, while the
line between the colors is sharp, in reality the tissue change may not be as
abrupt. Pixels falling
I S above the designated threshold may be very similar to the selected tumor
class yet are not
highlighted. The user should be more suspicious of pixels whose distance
values lie just above
the threshold, than those pixels whose distance values far exceed it, yet this
information is not
available in the binary image of Figure 6B. Figure 6A, on the other hand,
clearly shows to a
user the tissues that are in the same class as the training set and those
that, while not the same
class, are so close as to be very similar and suspected of being a tumor. On
the other hand,
viewing Figure 6B, a user has the advantage that stark contrast between all
tumor tissue and all
other tissue is easily seen.
In addition to directly presenting the similarity images to the user, as
portrayed
in step 34 of Figure 2 and Figure 6A, other display modes are envisioned. In
one variation,
the subset of pixels whose similarity values fall above or below a designated
threshold level
could be overlaid on the original image. Also, to indicate pixels included
within a volume, a
modified similarity image could be created, such that the calculated
similarity values are
displayed for all pixels whose values fall above or below a designated
threshold level, while a
constant similarity value is assigned to all other pixels. Similarity images
could be
reconstructed and displayed for image slices that were not originally acquired
(e.g.,
orthogonal slices). In another variation, the similarity images could be
volume rendered with
27


WO 01/39123 CA 02391289 2002-05-10 pCT~S00/32204
arbitrary slicing and high/low transparency values. Surface rendering at
particular similarity
values could be implemented.
Figures 7A and 7B illustrate a technique by which the threshold may be
dynamically varied by the user during viewing of the MR image. According to
this
embodiment, the automatic threshold which has been previously described is
assigned as the
beginning threshold. A first classification is done using the automatic
threshold and the
techniques as previously described. In a further embodiment of the present
invention, the
user is given control over this threshold so that it becomes a dynamic
threshold which is user-
controllable while the MR image is viewed on the screen. The user thus has the
capability to
modify this threshold to make it larger and thus include more data elements
within the
selected class or, to make it smaller and thus make it more difficult for data
elements to be
within the class. The user can thus dynamically vary the sensitivity of the
class segmentation
to select that image which has the lowest number of false positives, while
having an accurate
count of the true positives. This would permit the tissue classification
results to be viewed
across the full range from maximum sensitivity to maximum specificity.
One method for giving the user access is providing a slider bar as part of a
window display of the image. Movement of the slider bar dynamically alters the
threshold
value, the effect of which is immediately visually displayed to the user in
the displayed
image. Referring to Figures 7A-7B, depicted therein is a window display 81 of
an image 83
having a scale 80 on the side. A slider bar 82 is on scale 80 that can be
moved by the user
under control of a cursor on a mouse or keyboard. At the bottom end of the
scale 80 is
indicated a numerical value 84 which corresponds to the threshold value at the
lowest end of
the scale. At the upper end is a top number 86 which corresponds to the
numerical value of
the threshold value at the highest end of the scale. In this case, the
threshold numbers are 0.1
and 31.14, respectively, but the values can be different for each sample.
The position of the slider 82 on the scale under the automatic threshold value
is placed on the position on the scale which corresponds to that automatic
threshold value.
This may be a high, or low value depending on the relationship of data
elements in the
training set to each other as has been described.
Figure 7A illustrates an example in which the training set data elements are
quite similar to each other and thus, slider bar 82 is near the bottom
indicating a low
threshold number. For this low threshold, only those tissues which are very
similar to each
28


WO 01/39123 CA 02391289 2002-05-10 pCT~S00/32204
other will be considered within the same class as the training set. Thus,
using this threshold
number, two sites of similar tissue, 88 and 90 were identified as potentially
being the same
type of tissue, and thus likely candidates for a spreading tumor at two
locations. With this
low threshold, the region 90 is a very small region and appears as a single
speck. It is
difficult for the physician to determine whether this represents similar type
tissue or not and if
so, the size of the tissue at region 90. According to the present invention,
the physician is
able to move the slider 82 upward in order to increase the threshold number,
to thus
dynamically vary the threshold. As the threshold is increased, the region 90
becomes
significantly larger, as does region 88, see Figure 7B. This provides a clear
definition to the
physician that region 90 is a similar type tissue and indicates the exact
size. Of course, the
physician may move the slider bar higher in order to further increase the
threshold number to
include more tissue types. However, doing so will cause spurious signals which
may easily
recognized as false positives. Accordingly, the dynamic threshold may be
adjusted back
downward using the slider bar 82 to that location which most accurately
reflects the locations
of the tissue of concern.
Of some importance, the region 92 becomes highlighted in Figure 7B when it
was not shown to be in the same class of tissue in the first Figure 7A when
shown as a gray
scale pattern. Thus, region 92 which may have been suspected of being a tumor
site in the
gray scale image of Figure 7A is clearly shown to be of the same tissue, and
is displayed as
belonging to the same class as tissues 88 and 90. Thus, the physician has
confirmed that the
tumor has spread to a third location which was not apparent viewing the gray
scale image of
Figure 7A. Other potential sites for the tumor, locations 91 and 93 of Figure
7A, however,
are not highlighted and the physician is able to confirm that the tumor has
not spread to
locations 91 or 93. Thus, the use of the dynamic threshold is beneficial to
illustrate those
areas of the tissue which are most similar to each other and represent the
same tissue type
while also indicating those areas of the tissues which are in fact not similar
to each other even
though, at a first glance of a gray scale pattern they may appear similar in
many ways.
A user friendly computer screen can be provided as shown in Figures 8A-8C
according to the present invention to provide other advantages for the
physician. As
indicated in Figure 8A, the classification threshold can be changed by moving
slider bar 114.
In the example shown in Figure 8A, the actual value of the threshold number
17, which
corresponds to the position as represented by the slider bar 82. For example,
in Figure 8A the
29


CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
actual threshold numeric value is 17 whereas in Figure 8B, the numeric value
has been
increased to 35 as shown in above bar 114. The user may easily click on the
arrow on slider
bar 114 to move the threshold to any desired location. Also, the system may be
returned to
the custom threshold number previously calculated by clicking on the box 118
labeled
"default" and thus return to the automatic classification technique if
desired. The alow on
slider bar 114 may be moved as desired to increase or decrease the threshold
values. The
computer screen also illustrates the ease of use of the present invention for
the radiologist. A
patient name box 100 is provided which provides the patient's name. The time
and date that
the data was collected is shown in box 102. Indicated in box 101 is the slice
number and in
box 103, the number of slices available for viewing. Box 104 permits a user to
sort the
various slices or to select the type of sample to be studied. Box 106 permits
a user to turn on
or off the overlay features. Box 108 permits the user to indicate that a
region of interest is
going to be created corresponding to the region of interest step 38 of Figure
2. Cluster
selection is carried out within this region of interest by clicking on box 108
and guided tissue
selection can be carried out by clicking on box 112, corresponding to steps 40
and 42 of
Figure 2.
The user can also achieve other functions using tool bar 110 such as clearing
prior settings, box 108, zooming out, applying different masks, or other
automatic features as
indicated by the boxes. The screen is also advantageous in that it provides to
the user
detailed information regarding the exact view currently under consideration.
Box 1120
indicates the correspondence of the test sample color to the training set
color
The screen can also show, side-by-side, the images with the overlay and the
images without the overlay. Thus, the figure on the left hand side is the
unmodified MR
image with potential tumor sites 120, 122, 126, 128 and 140. A radiologist may
have
difficulty determining tumor from non-tumor locations in the conventional
image. With the
invention applied, the tumor sites and non-tumor sites are more readily seen.
Thus, region
120 is clearly seen as tumor. By setting the threshold to 35, as shown in
Figure 8B, regions
122 and 140 can clearly be seen as tumor sites, similar to region 120 whereas
regions 126 and
128 can be seen as fluid ducts, not tumor sites. The correct diagnosis can
thus be made more
quickly and with better certainty. Figure 8C provide a full color similarity
image. A rainbow
scale 115 is provided below the slider bar 114 to show the color range of the
image. The


CA 02391289 2002-05-10
WO 01/39123 PCT/US00/32204
tumor site clearly shows as a dark red in region 120. Of the other potential
sites, regions 122
and 140 have a small red center with a fringe color of yellow then green. This
indicates they
are likely tumor sites. Yet, regions 126 and 128 remain the same color,
indicating there is not
tumor present at these locations. Thus, the present invention provides an easy
to use
computer screen readout which may be manipulated by the radiologist for a
clear
understanding of the tissues under investigation.
While different embodiments of the invention have been illustrated and
described, it is to be understood that various changes may be made therein
without departing
from the spirit and scope of the invention. As will be evident from the
foregoing, the disclosed
embodiments consider a single tissue at each time or each tissue
independently, instead of
classifying all tissues at one time. This enables modification of the score
data as described
above. Prior segmentation methods attempt to segment all present tissues, thus
generating a
score at each pixel location for all of the tissue classes. Data is
thresholded usually by
classifying the tissue by the lowest distance score and/or highest membership
value, and is
generally fixed and not adjustable by the user. However, the embodiments of
the present
invention disclosed herein can be integrated within a traditional method of
segmentation.
When all samples are modeled a threshold could be set for one or more sample
groups allowing
the sensitivity to be changed on a group by group basis.
Thus, from the foregoing it will be appreciated that, although specific
embodiments of the invention have been described herein for purposes of
illustration, various
modifications may be made without deviating from the spirit and scope of the
invention.
Accordingly, the invention is not limited except as by the appended claims.
31

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date Unavailable
(86) PCT Filing Date 2000-11-24
(87) PCT Publication Date 2001-05-31
(85) National Entry 2002-05-10
Dead Application 2004-11-24

Abandonment History

Abandonment Date Reason Reinstatement Date
2003-11-24 FAILURE TO PAY APPLICATION MAINTENANCE FEE

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Registration of a document - section 124 $100.00 2002-05-10
Application Fee $150.00 2002-05-10
Maintenance Fee - Application - New Act 2 2002-11-25 $50.00 2002-05-10
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
CONFIRMA, INC.
Past Owners on Record
STORK, CHRISTOPHER L.
WYMAN, BRADLEY T.
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Representative Drawing 2002-10-17 1 7
Description 2002-05-10 31 1,807
Abstract 2002-05-10 2 70
Claims 2002-05-10 2 68
Drawings 2002-05-10 11 363
Cover Page 2002-10-18 1 42
PCT 2002-05-10 9 296
Assignment 2002-05-10 4 217
Correspondence 2002-10-15 1 21
Correspondence 2002-11-01 2 99
Assignment 2002-11-01 3 143
Assignment 2002-05-10 5 275
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Correspondence 2003-02-05 1 20
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Fees 2002-11-06 1 52
Correspondence 2003-01-17 1 27
Correspondence 2003-05-14 1 14