U.S. patent application number 14/519547 was filed with the patent office on 2015-03-05 for systems and methods for predicting location, onset, and/or change of coronary lesions.
The applicant listed for this patent is HeartFlow, Inc.. Invention is credited to Gilwoo CHOI, Leo GRADY, Charles A. TAYLOR.
Application Number | 20150065847 14/519547 |
Document ID | / |
Family ID | 52472572 |
Filed Date | 2015-03-05 |
United States Patent
Application |
20150065847 |
Kind Code |
A1 |
CHOI; Gilwoo ; et
al. |
March 5, 2015 |
SYSTEMS AND METHODS FOR PREDICTING LOCATION, ONSET, AND/OR CHANGE
OF CORONARY LESIONS
Abstract
Systems and methods are disclosed for predicting the location,
onset, or change of coronary lesions from factors like vessel
geometry, physiology, and hemodynamics. One method includes:
acquiring, for each of a plurality of individuals, a geometric
model, blood flow characteristics, and plaque information for part
of the individual's vascular system; training a machine learning
algorithm based on the geometric models and blood flow
characteristics for each of the plurality of individuals, and
features predictive of the presence of plaque within the geometric
models and blood flow characteristics of the plurality of
individuals; acquiring, for a patient, a geometric model and blood
flow characteristics for part of the patient's vascular system; and
executing the machine learning algorithm on the patient's geometric
model and blood flow characteristics to determine, based on the
predictive features, plaque information of the patient for at least
one point in the patient's geometric model.
Inventors: |
CHOI; Gilwoo; (Mountain
View, CA) ; GRADY; Leo; (Millbrae, CA) ;
TAYLOR; Charles A.; (Menlo Park, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
HeartFlow, Inc. |
Redwood City |
CA |
US |
|
|
Family ID: |
52472572 |
Appl. No.: |
14/519547 |
Filed: |
October 21, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14011151 |
Aug 27, 2013 |
|
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14519547 |
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Current U.S.
Class: |
600/407 |
Current CPC
Class: |
G06T 2207/30096
20130101; G16H 50/20 20180101; G06N 20/00 20190101; G06T 2207/30101
20130101; G06F 19/00 20130101; G06T 2207/10081 20130101; G06K 9/66
20130101; G06T 2207/10088 20130101; G06T 2207/10104 20130101; A61B
5/7275 20130101; G06K 9/4604 20130101; G06N 7/005 20130101; G06T
7/0012 20130101; G06T 2207/10132 20130101; G06T 2207/10108
20130101; G06T 2207/30104 20130101; G16H 50/50 20180101; A61B
5/02007 20130101 |
Class at
Publication: |
600/407 |
International
Class: |
A61B 5/02 20060101
A61B005/02; A61B 5/00 20060101 A61B005/00 |
Claims
1-29. (canceled)
30. A computer-implemented method for predicting information
relating to a vascular lesion of an individual, the method
comprising: receiving an image of the individual's vasculature;
acquiring a geometric model of the individual's vasculature, one or
more physiological or phenotypic parameters of the individual, and
one or more biophysical hemodynamic characteristics associated with
the individual's vasculature; creating one or more associations
between the one or more physiological or phenotypic parameters of
the individual, the one or more biophysical hemodynamic
characteristics of the individual, and each of a plurality of
points in the geometric model; estimating, using a processor, a
probability of artery disease at each of the plurality of points in
the geometric model of the individual's vasculature using the one
or more associations and plaque information associated with one or
more individuals of a plurality of individuals; and generating an
electronic display including the probability of artery disease.
31. The method of claim 30, wherein the probability includes a
prediction of one or more locations of coronary lesions, plaque
growth or shrinkage, pathogenesis, or a combination thereof.
32. The method of claim 30, wherein the plaque information includes
one or more measurements of coronary plaque composition, burden, or
location.
33. The method of claim 30, further comprising: acquiring the
geometric model of the individual's vasculature, the one or more
physiological or phenotypic parameters of the individual, or the
one or more biophysical hemodynamic characteristics associated with
the individual's vasculature at multiple time points.
34. The method of claim 30, further comprising: computing, for the
one or more physiological or phenotypic parameters of the
individual, global and local physiological or phenotypic parameters
associated with the geometric model, wherein the global
physiological or phenotypic parameters apply to the entire
geometric model of the individual's vasculature and the local
physiological or phenotypic parameters vary across the geometric
model of the individual's vasculature.
35. The method of claim 30, wherein the geometric model of the
individual's vasculature includes a geometric representation of one
or more of blood vessels, myocardium, aorta, valves, plaques, and
chambers.
36. The method of claim 30, further comprising: acquiring, for the
one or more individuals of the plurality of individuals,
physiological parameters, phenotypic parameters, or biophysical
hemodynamic characteristics, wherein the probability of artery
disease is further based on the physiological parameters, the
phenotypic parameters, or the biophysical hemodynamic
characteristics associated with the one or more individuals of the
plurality of individuals.
37. The method of claim 36, wherein the biophysical hemodynamic
characteristics are based on computational fluid dynamics
analysis.
38. A system for predicting information relating to a coronary
lesion, the system comprising: a data storage device storing
instructions for predicting information relating to a coronary
lesion; and a processor configured to execute the instructions to
perform a method including: receiving an image of the individual's
vasculature; acquiring a geometric model of the individual's
vasculature, one or more physiological or phenotypic parameters of
the individual, and one or more biophysical hemodynamic
characteristics associated with the individual's vasculature;
creating one or more associations between the one or more
physiological or phenotypic parameters of the individual, the one
or more biophysical hemodynamic characteristics of the individual,
and each of a plurality of points in the geometric model;
estimating, using a processor, a probability of artery disease at
each of the plurality of points in the geometric model of the
individual's vasculature using the one or more associations and
plaque information associated with one or more individuals of a
plurality of individuals; and generating an electronic display
including the probability of artery disease.
39. The system of claim 38, wherein the probability includes a
prediction of one or more locations of coronary lesions, plaque
growth or shrinkage, pathogenesis, or a combination thereof.
40. The system of claim 38, wherein the plaque information includes
one or more measurements of coronary plaque composition, burden, or
location.
41. The system of claim 38, further comprising: acquiring the
geometric model of the individual's vasculature, the one or more
physiological or phenotypic parameters of the individual, or the
one or more biophysical hemodynamic characteristics associated with
the individual's vasculature at multiple time points.
42. The system of claim 41, wherein the system is further
configured for: computing, for the one or more physiological or
phenotypic parameters of the individual, global and local
physiological or phenotypic parameters associated with the
geometric model, wherein the global physiological or phenotypic
parameters apply to the entire geometric model of the individual's
vasculature and the local physiological or phenotypic parameters
vary across the geometric model of the individual's
vasculature.
43. The system of claim 38, wherein the geometric model of the
individual's vasculature includes a geometric representation of one
or more of blood vessels, myocardium, aorta, valves, plaques, and
chambers.
44. The system of claim 9, wherein the system is further configured
for: acquiring, for the one or more individuals of the plurality of
individuals, physiological parameters, phenotypic parameters, or
biophysical hemodynamic characteristics, wherein the probability of
artery disease is further based on the physiological parameters,
the phenotypic parameters, or the biophysical hemodynamic
characteristics associated with the one or more individuals of the
plurality of individuals.
45. The system of claim 44, wherein the biophysical hemodynamic
characteristics are based on computational fluid dynamics
analysis.
46. A non-transitory computer readable medium for use on a computer
system containing computer-executable programming instructions for
performing a method of predicting information relating to a
coronary lesion, the method comprising: receiving an image of the
individual's vasculature; acquiring a geometric model of the
individual's vasculature, one or more physiological or phenotypic
parameters of the individual, and one or more biophysical
hemodynamic characteristics associated with the individual's
vasculature; creating one or more associations between the one or
more physiological or phenotypic parameters of the individual, the
one or more biophysical hemodynamic characteristics of the
individual, and each of a plurality of points in the geometric
model; estimating, using a processor, a probability of artery
disease at each of the plurality of points in the geometric model
of the individual's vasculature using the one or more associations
and plaque information associated with one or more individuals of a
plurality of individuals; and generating an electronic display
including the probability of artery disease.
47. The non-transitory computer readable medium of claim 46,
wherein the probability includes a prediction of one or more
locations of coronary lesions, plaque growth or shrinkage,
pathogenesis, or a combination thereof.
48. The non-transitory computer readable medium of claim 46,
wherein the plaque information includes one or more measurements of
coronary plaque composition, burden, or location.
49. The non-transitory computer readable medium of claim 46,
further comprising: acquiring the geometric model of the
individual's vasculature, the one or more physiological or
phenotypic parameters of the individual, or the one or more
biophysical hemodynamic characteristics associated with the
individual's vasculature at multiple time points.
Description
FIELD OF THE INVENTION
[0001] Various embodiments of the present disclosure relate
generally to medical imaging and related methods. More
specifically, particular embodiments of the present disclosure
relate to systems and methods for predicting the location, onset,
and/or change of coronary lesions from factors such as vessel
geometry, physiology, and hemodynamics.
BACKGROUND
[0002] Coronary artery disease ("CAD") may produce coronary
lesions, such as a stenosis (abnormal narrowing of a blood vessel),
in the blood vessels providing blood to the heart. As a result,
blood flow to the heart may be restricted. A patient suffering from
coronary artery disease may experience chest pain, referred to as
"chronic stable angina" during physical exertion, or "unstable
angina" when the patient is at rest. A more severe manifestation of
disease may lead to myocardial infarction, or heart attack.
[0003] A need exists to provide more accurate data relating to
coronary lesions, e.g., size, shape, location, functional
significance (e.g., whether the lesion impacts blood flow), etc.
Patients suffering from chest pain and/or exhibiting symptoms of
coronary artery disease may be subjected to one or more tests that
may provide some indirect evidence relating to coronary lesions.
For example, noninvasive tests may include electrocardiograms,
biomarker evaluation from blood tests, treadmill tests,
echocardiography, single positron emission computed tomography
(SPECT), positron emission tomography (PET), and coronary computed
tomographic angiography (CCTA). The noninvasive tests may provide
indirect evidence of coronary lesions by looking for changes in
electrical activity of the heart (e.g., using electrocardiography
(ECG)), motion of the myocardium (e.g., using stress
echocardiography), perfusion of the myocardium (e.g., using PET or
SPECT), or metabolic changes (e.g., using biomarkers). However,
these noninvasive tests typically do not provide a direct
assessment of coronary lesions or assess blood flow rates. Thus,
patients may also require an invasive test, such as diagnostic
cardiac catheterization, to visualize coronary lesions. Diagnostic
cardiac catheterization may include performing conventional
coronary angiography (CCA) to gather anatomic data on coronary
lesions by providing a doctor with an image of the size and shape
of the arteries.
[0004] However, both invasive and noninvasive tests for CAD are
only useful in determining an amount of disease and/or risk of
heart attack that has already been incurred. That is, tests for CAD
are unable to predict future amounts of plaque build-up, stenosis,
or other CAD that is likely to occur based on other known
characteristics of an individual. Even though CAD is known to be
associated with various risk factors, including smoking, diabetes,
hypertension, and dietary habits, no techniques exist for
predicting the onset of CAD. In addition, no techniques exist for
predicting the type or location of plaque that is likely to develop
in view of other known characteristics of an individual.
[0005] Consequently, the present disclosure describes new
approaches for predicting the location, onset, and/or change of
coronary lesions from factors such as vessel geometry, physiology,
and hemodynamics.
SUMMARY
[0006] Systems and methods are disclosed for predicting the
location, onset, and/or change of coronary lesions from factors
such as vessel geometry, physiology, and hemodynamics.
[0007] According to one embodiment, a method is disclosed for
predicting information relating to a coronary lesion. The method
includes: acquiring, for each of a plurality of individuals, a
geometric model, blood flow characteristics, and plaque information
for at least part of the individual's vascular system; identifying,
for each of a plurality of points in the geometric models, features
predictive of the presence of plaque within the geometric models
and blood flow characteristics of the plurality of individuals;
training a machine learning algorithm based on the geometric models
and blood flow characteristics for each of the plurality of
individuals, and the predictive features; acquiring, for a patient,
a geometric model and blood flow characteristics for at least part
of the patient's vascular system; and executing the machine
learning algorithm on the patient's geometric model and blood flow
characteristics to determine, based on the predictive features,
plaque information of the patient for at least one point in the
patient's geometric model.
[0008] According to another embodiment, a system is disclosed for
predicting information relating to a coronary lesion. The system
includes a data storage device storing instructions for predicting
information relating to a coronary lesion; and a processor
configured to execute the instructions to perform a method
including the steps of: acquiring, for each of a plurality of
individuals, a geometric model, blood flow characteristics, and
plaque information for at least part of the individual's vascular
system; identifying, for each of a plurality of points in the
geometric models, features predictive of the presence of plaque
within the geometric models and blood flow characteristics of the
plurality of individuals; training a machine learning algorithm
based on the geometric models and blood flow characteristics for
each of the plurality of individuals, and the predictive features;
acquiring, for a patient, a geometric model and blood flow
characteristics for at least part of the patient's vascular system;
and executing the machine learning algorithm on the patient's
geometric model and blood flow characteristics to determine, based
on the predictive features, plaque information of the patient for
at least one point in the patient's geometric model.
[0009] According to another embodiment, a non-transitory
computer-readable medium is disclosed storing instructions that,
when executed by a computer, cause the computer to perform a method
for predicting information relating to a coronary lesion, the
method including: acquiring, for each of a plurality of
individuals, a geometric model, blood flow characteristics, and
plaque information for at least part of the individual's vascular
system; identifying, for each of a plurality of points in the
geometric models, features predictive of the presence of plaque
within the geometric models and blood flow characteristics of the
plurality of individuals; training a machine learning algorithm
based on the geometric models and blood flow characteristics for
each of the plurality of individuals, and the predictive features;
acquiring, for a patient, a geometric model and blood flow
characteristics for at least part of the patient's vascular system;
and executing the machine learning algorithm on the patient's
geometric model and blood flow characteristics to determine, based
on the predictive features, plaque information of the patient for
at least one point in the patient's geometric model.
[0010] According to another embodiment, a computer-implemented
method is disclosed for predicting information relating to a
coronary lesion. One method includes acquiring, over a network, for
a patient, a geometric model and blood flow characteristics for at
least part of the patient's vascular system; and determining plaque
information of the patient for at least one point in the patient's
geometric model by executing on the patient's geometric model and
blood flow characteristics, a machine learning algorithm trained
based on plaque predictive features derived from geometric models,
blood flow characteristics, and plaque information obtained for
each of a plurality of individuals.
[0011] Additional objects and advantages of the disclosed
embodiments will be set forth in part in the description that
follows, and in part will be apparent from the description, or may
be learned by practice of the disclosed embodiments. The objects
and advantages of the disclosed embodiments will be realized and
attained by means of the elements and combinations particularly
pointed out in the appended claims.
[0012] It is to be understood that both the foregoing general
description and the following detailed description are exemplary
and explanatory only and are not restrictive of the disclosed
embodiments, as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The accompanying drawings, which are incorporated in and
constitute a part of this specification, illustrate various
exemplary embodiments and together with the description, serve to
explain the principles of the disclosed embodiments.
[0014] FIG. 1 is a block diagram of an exemplary system and network
for predicting the location, onset, and/or change of coronary
lesions from factors such as vessel geometry, physiology, and
hemodynamics, according to an exemplary embodiment of the present
disclosure.
[0015] FIG. 2 is a diagram of an exemplary three-dimensional mesh
of a geometric model used in predicting the location, onset, and/or
change of coronary lesions from factors such as vessel geometry,
physiology, and hemodynamics, according to an exemplary embodiment
of the present disclosure.
[0016] FIG. 3A is a block diagram of an exemplary method of
training a machine learning system for predicting the location,
onset, and/or change of coronary lesions from factors such as
vessel geometry, physiology, and hemodynamics s, according to an
exemplary embodiment of the present disclosure.
[0017] FIG. 3B is a block diagram of an exemplary method of using a
trained machine learning system for predicting the location, onset,
and/or change of coronary lesions from factors such as vessel
geometry, physiology, and hemodynamics, according to an exemplary
embodiment of the present disclosure.
[0018] FIG. 4A is a block diagram of an exemplary method of
training a machine learning system for predicting the location of
coronary lesions from factors such as vessel geometry, physiology,
and hemodynamics, according to an exemplary embodiment of the
present disclosure.
[0019] FIG. 4B is a block diagram of an exemplary method of using a
trained machine learning system for predicting the location of
coronary lesions from factors such as vessel geometry, physiology,
and hemodynamics, according to an exemplary embodiment of the
present disclosure.
[0020] FIG. 5A is a block diagram of an exemplary method of
training a machine learning system for predicting the onset and/or
change (e.g., rate of growth/shrinkage) of coronary lesions from
vessel geometry, physiology, and hemodynamics, according to an
exemplary embodiment of the present disclosure.
[0021] FIG. 5B is a block diagram of an exemplary method of using a
trained machine learning system for predicting the onset and/or
change (e.g., rate of growth/shrinkage) of coronary lesions from
vessel geometry, physiology, and hemodynamics, according to an
exemplary embodiment of the present disclosure.
[0022] FIG. 6 is a simplified block diagram of an exemplary
computer system in which embodiments of the present disclosure may
be implemented.
DESCRIPTION OF THE EMBODIMENTS
[0023] Reference will now be made in detail to the exemplary
embodiments of the disclosure, examples of which are illustrated in
the accompanying drawings. Wherever possible, the same reference
numbers will be used throughout the drawings to refer to the same
or like parts.
[0024] The present disclosure describes an approach for providing
prognosis of coronary artery disease ("CAD") and for predicting
plaque growth/shrinkage based on patient-specific geometry and
blood flow characteristics. Specifically, the present disclosure
describes a system that receives patient information (e.g., 3D
cardiac imaging, patient demographics, and history) and provides a
patient-specific and location-specific risk score for the
pathogenesis of CAD. Although the present disclosure is described
with particular reference to coronary artery disease, the same
systems and methods are applicable to creating a patient-specific
prediction of lesion formation in other vascular systems beyond the
coronary arteries.
[0025] More specifically, the present disclosure describes certain
principles and embodiments for using patients' cardiac imaging to:
(1) derive a patient-specific geometric model of the coronary
vessels; and (2) perform coronary flow simulation to extract
hemodynamic characteristics, patient physiological information, and
boundary conditions in order to predict the onset and location of
coronary lesions. The present disclosure is not limited to a
physics-based simulation of blood flow to predict the locations
predisposed to plaque formation, but rather uses machine learning
to predict the lesion location by incorporating various risk
factors, including patient demographics and coronary geometry, as
well as the results of patient-specific biophysical simulations
(e.g., hemodynamic characteristics). If additional diagnostic test
results are available, those results may also be used in the
training and prediction. According to certain embodiments, the
presently disclosed methods involve two phases: (1) a training
phase in which the machine learning system is trained to predict
one or more locations of coronary lesions, and (2) a production
phase in which the machine learning system is used to produce one
or more locations of coronary lesions.
[0026] Referring now to the figures, FIG. 1 depicts a block diagram
of an exemplary system and network for predicting the location,
onset, and/or change of coronary lesions from vessel geometry,
physiology, and hemodynamics. Specifically, FIG. 1 depicts a
plurality of physician devices or systems 102 and third party
provider devices or systems 104, any of which may be connected to
an electronic network 101, such as the Internet, through one or
more computers, servers, and/or handheld mobile devices. Physicians
and/or third party providers associated with physician devices or
systems 102 and/or third party provider devices or systems 104,
respectively, may create or otherwise obtain images of one or more
patients' cardiac and/or vascular systems. The physicians and/or
third party providers may also obtain any combination of
patient-specific information, such as age, medical history, blood
pressure, blood viscosity, etc. Physicians and/or third party
providers may transmit the cardiac/vascular images and/or
patient-specific information to server systems 106 over the
electronic network 101. Server systems 106 may include storage
devices for storing images and data received from physician devices
or systems 102 and/or third party provider devices or systems 104.
Server systems 106 may also include processing devices for
processing images and data stored in the storage devices.
[0027] FIG. 2 is a diagram of an exemplary three-dimensional mesh
of a geometric model 200 used in predicting the location, onset,
and/or change of coronary lesions from vessel geometry, according
to an exemplary embodiment of the present disclosure. For example,
as described above, a third party provider or physician may obtain
patient-specific anatomical data of one or more patients.
Patient-specific anatomical data may include data regarding the
geometry of the patient's heart, e.g., at least a portion of the
patient's aorta, a proximal portion of the main coronary arteries
(and the branches extending therefrom) connected to the aorta, and
the myocardium. However, as-described above, patient-specific
anatomical data may also or alternatively be obtained in relation
to any portion of the patient's vasculature, including beyond the
patient's heart.
[0028] Initially, a patient may be selected, e.g., when the
physician determines that information about the patient's coronary
blood flow is desired, e.g., if the patient is experiencing
symptoms associated with coronary artery disease, such as chest
pain, heart attack, etc. The patient-specific anatomical data may
be obtained noninvasively, e.g., using a noninvasive imaging
method. For example, CCTA is an imaging method in which a user may
operate a computer tomography (CT) scanner to view and create
images of structures, e.g., the myocardium, the aorta, the main
coronary arteries, and other blood vessels connected thereto. The
CCTA data may be time-varying, e.g., to show changes in vessel
shape over a cardiac cycle. CCTA may be used to produce an image of
the patient's heart. For example, 64-slice CCTA data may be
obtained, e.g., data relating to 64 slices of the patient's heart,
and assembled into a three-dimensional image.
[0029] Alternatively, other noninvasive imaging methods, such as
magnetic resonance imaging (MRI) or ultrasound (US), or invasive
imaging methods, such as digital subtraction angiography (DSA), may
be used to produce images of the structures of the patient's
anatomy. The imaging methods may involve injecting the patient
intravenously with a contrast agent to enable identification of the
structures of the anatomy. The resulting imaging data (e.g.,
provided by CCTA, MRI, etc.) may be provided by a third-party
vendor, such as a radiology lab or a cardiologist, by the patient's
physician, etc.
[0030] Other patient-specific anatomical data may also be
determined from the patient noninvasively. For example,
physiological data such as the patient's blood pressure, baseline
heart rate, height, weight, hematocrit, stroke volume, etc., may be
measured. The blood pressure may be the blood pressure in the
patient's brachial artery (e.g., using a pressure cuff), such as
the maximum (systolic) and minimum (diastolic) pressures.
[0031] The patient-specific anatomical data obtained as described
above may be transferred over a secure communication line (e.g.,
via electronic network 101 of FIG. 1). For example, the data may be
transferred to server systems 106 or other computer system for
performing computational analysis, e.g., the computational analysis
described below with respect to FIGS. 3-5B. In one exemplary
embodiment, the patient-specific anatomical data may be transferred
to server systems 106 or other computer system operated by a
service provider providing a web-based service. Alternatively, the
data may be transferred to a computer system operated by the
patient's physician or other user.
[0032] In one embodiment, server systems 106 may generate a
three-dimensional solid model and/or three-dimensional mesh 200
based on the received patient-specific anatomical data. For
example, server systems 106 may generate the three-dimensional
model and/or mesh based on any of the techniques described in U.S.
Pat. No. 8,315,812 by Taylor et al., which issued on Nov. 20, 2012,
the entirety of which is hereby incorporated herein by
reference.
[0033] FIG. 3A is a block diagram of an exemplary method 300 for
training a machine learning system, based on a plurality of
patients' blood flow characteristics and geometry, for predicting
the location, onset, and/or change of coronary lesions from vessel
geometry, physiology, and hemodynamics, according to an exemplary
embodiment of the present disclosure. Specifically, as shown in
FIG. 3A, method 300 may include obtaining patient imaging data
(e.g., a geometric model) and physiologic and/or hemodynamic
information 302 for a plurality of patients. Method 300 may include
generating feature vectors 304 based on the plurality of patients'
imaging and physiologic and/or hemodynamic information. Method 300
further includes obtaining information about plaque 306 for the
plurality of patients, and formatting the information about the
plurality of patients' plaque into the format that is desired of
the output 308 of the learning system. Method 300 completes the
training mode by inputting into a learning system 310 both the
feature vectors 304 formed from the plurality of patients' imaging
data and physiologic and/or hemodynamic information, and the output
308 of the information about plaque for the plurality of patients.
For example, as will be described in more detail below, any
suitable type of machine learning system may process both the
feature vectors 304 and outputs 308 to identify patterns and
conclusions from that data, for later use in producing outputs of
information about a particular user's plaque.
[0034] FIG. 3B is a block diagram of an exemplary method 350 for
using the trained machine learning system 310 for predicting, for a
particular patient, the location, onset, and/or change of coronary
lesions from vessel geometry, physiology, and hemodynamics,
according to an exemplary embodiment of the present disclosure. As
shown in FIG. 3B, method 350 may include obtaining patient imaging
data (e.g., a geometric model) and physiologic and/or hemodynamic
information 312 for a particular patient, for whom it is desired to
predict plaque location, onset, and/or change based on the trained
learning system 310. Of course, method 350 may include obtaining
the patient imaging data and physiologic and/or hemodynamic
information for any number of patients for whom it is desired to
predict plaque location, onset, and/or change based on the trained
learning system. Method 350 may include generating a feature vector
314 for each of a plurality of points of the patient's geometric
model, based on one or more elements of the received physiologic
and/or hemodynamic information. Method 350 may then include
operating the machine learning system 310 on the feature vectors
generated for the patient to obtain an output 316 of the estimates
of the presence or onset of plaque at each of a plurality of points
in the patient's geometric model, and translating the output into
useable information 318 about the location, onset, and/or change of
plaque in the patient 318.
[0035] Described below are exemplary embodiments for implementing a
training mode method 300 and a production mode method 350 of
machine learning for predicting the location, onset, and/or change
of coronary lesions from vessel geometry, physiology, and
hemodynamics, e.g. using server systems 106, based on images and
data received from physicians and/or third party providers over
electronic network 101. Specifically, the methods of FIGS. 4A-5B
may be performed by server systems 106, based on information
received from physician devices or systems 102 and/or third party
provider devices or systems 104 over electronic network 101.
[0036] FIG. 4A is a block diagram of an exemplary method 400 for
training a machine learning system (e.g., a machine learning system
310 executed on server systems 106) for predicting the location of
coronary lesions from vessel geometry, physiology, and
hemodynamics, according to an exemplary embodiment of the present
disclosure. Specifically, method 400 may include, for one or more
patients (step 402), obtaining a patient-specific geometric model
of a portion of the patient's vasculature (step 404), obtaining one
or more estimates of physiological or phenotypic parameters of the
patient (step 406), and obtaining one or more estimates of
biophysical hemodynamic characteristics of the patient (step
408).
[0037] For example, the step of obtaining a patient-specific
geometric model of a portion of the patient's vasculature (step
404) may include obtaining a patient-specific model of the geometry
for one or more of the patient's blood vessels, myocardium, aorta,
valves, plaques, and/or chambers. In one embodiment, this geometry
may be represented as a list of points in space (possibly with a
list of neighbors for each point) in which the space can be mapped
to spatial units between points (e.g., millimeters). In one
embodiment, this model may be derived by performing a cardiac CT
imaging of the patient in the end diastole phase of the cardiac
cycle. This image then may be segmented manually or automatically
to identify voxels belonging to the aorta and the lumen of the
coronary arteries. Given a 3D image of coronary vasculature, any of
the many available methods may be used for extracting a
patient-specific model of cardiovascular geometry. Inaccuracies in
the geometry extracted automatically may be corrected by a human
observer who compares the extracted geometry with the images and
makes corrections as needed. Once the voxels are identified, the
geometric model can be derived (e.g., using marching cubes).
[0038] The step of obtaining one or more estimates of physiological
or phenotypic parameters of the patient (step 406) may include
obtaining a list of one or more estimates of physiological or
phenotypic parameters of the patient, such as blood pressure, blood
viscosity, in vitro blood test results (e.g., LDL/Triglyceride
cholesterol level), patient age, patient gender, the mass of the
supplied tissue, etc. These parameters may be global (e.g., blood
pressure) or local (e.g., estimated density of the vessel wall at a
location). In one embodiment, the physiological or phenotypic
parameters may include, blood pressure, hematocrit level, patient
age, patient gender, myocardial mass (e.g., derived by segmenting
the myocardium in the image, and calculating the volume in the
image and using an estimated density of 1.05 g/mL to estimate the
myocardial mass), general risk factors of coronary artery disease
(e.g., smoking, diabetes, hypertension, abdominal obesity, dietary
habits, family history, etc.), and/or in vitro blood test results
(e.g., LDL, Triglyceride cholesterol level).
[0039] The step of obtaining one or more estimates of biophysical
hemodynamic characteristics of the patient (step 408) may include
obtaining a list of one or more estimates of biophysical
hemodynamic characteristics from computational fluid dynamics
analysis, such as wall-shear stress, oscillatory shear index,
particle residence time, Reynolds number, Womersley number, local
flow rate, and turbulent kinetic energy, etc. Specifically, the
mean wall-shear stress, may be defined as
1 T 1 - T 0 .intg. T 0 T 1 t s t . ##EQU00001##
{right arrow over (t.sub.s)}, which may be the wall shear stress
vector defined as the in-plane component of the surface traction
vector. The oscillatory shear index (OSI), may be defined as
1 2 ( 1 - 1 T 1 - T 0 .intg. T 0 T 1 t s t 1 T 1 - T 0 .intg. T 0 T
1 t s t ) , ##EQU00002##
which may be a measure of the uni-directionality of shear stress.
The particle residence time may be a measure of the time it takes
blood to be flushed from a specified fluid domain. The turbulent
kinetic energy ("TKE") may be a measure of the intensity of
turbulence associated with eddies in turbulent flow, and may be
characterized by measured root-mean-square velocity fluctuation,
and may be normalized by kinetic energy. The Reynolds number may be
defined as
.rho. UD .mu. ##EQU00003##
where (.rho.: density of blood, U: average flow velocity, D: vessel
diameter, .mu.: dynamic viscosity). The Womersley number may be
defined as
D 2 .PI..rho. .mu. ##EQU00004##
where
( .PI. : angular frequency , equal to 1 cardiac cycle length ) .
##EQU00005##
[0040] Method 400 may further include obtaining an indication of
the presence or absence of plaque at one or more locations of the
patient-specific geometric model (step 410). For example, in one
embodiment, the location of calcified or non-calcified plaque may
be determined using CT and/or other imaging modalities, including
intravascular ultrasound, or optical coherence tomography. For
example, the plaque may be detected in the three-dimensional image
(200 of FIG. 2) generated from patient-specific anatomical data.
The plaque may be identified in a three-dimensional image or model
as areas that are lighter than the lumens of the aorta, the main
coronary arteries, and/or the branches. Thus, the plaque may be
detected by the computer system as having an intensity value below
a set value or may be detected visually by the user. The location
of detected plaques may be parameterized by a distance from the
ostium point (left main or right coronary ostium) to the projection
of centroid of plaque coordinates onto the associated vessel
centerline and an angular position of plaque with respect to
myocardium (e.g., myocardial/pericardial side). The location of
detected plaques may be also parameterized by start and end points
of the projection of plaque coordinates onto the associated vessel
centerline. If plaque exists at a location, method 400 may include
obtaining a list of one or more measurements of coronary plaque
composition, e.g., type, Hounsfield units ("HU"), etc., burden,
shape (eccentric or concentric), and location.
[0041] Method 400 may further include, for each of a plurality of
points in the patient-specific geometric model for which there is
information about the presence or absence of plaque (step 412),
creating a feature vector for the point (step 414) and associating
the feature vector with the presence or absence of plaque at that
point (step 416). In one embodiment, the step of creating a feature
vector for the point may include creating a feature vector for that
point that consists of a numerical description of the geometry and
biophysical hemodynamic characteristics at that point, and
estimates of physiological or phenotypic parameters of the patient.
For example, a feature vector for attributes: distance to ostium,
wall shear stress, local flow rate, Reynolds number, and centerline
curvature, may be in the form of (50 mm, 70 dyne/cm.sup.2, 1500
mm.sup.3/sec, 400, 1 mm.sup.-1). Global physiological or phenotypic
parameters may be used in the feature vector of all points, and
local physiological or phenotypic parameters may change in the
feature vector of different points.
[0042] In one embodiment, an exemplary feature vector generated in
step 414 may include one or more of: (i) systolic and diastolic
blood pressure, (ii) heart rate, (iii) blood properties including:
plasma, red blood cells (erythrocytes), hematocrit, white blood
cells (leukocytes) and platelets (thrombocytes), viscosity, yield
stress, etc. (iv) patient age, gender, height, weight, etc., (v)
lifestyle characteristics, e.g., presence or absence of current
medications/drugs, (vi) general risk factors of CAD, such as
smoking, diabetes, hypertension, abdominal obesity, dietary habits,
family history of CAD, etc., (vii) in vitro blood test results,
such as LDL, Triglyceride cholesterol level, etc., (viii) coronary
calcium score, (ix) amount of calcium in aorta and valve, (x)
presence of aortic aneurysm, (xi) presence of valvular heart
disease, (xii) presence of peripheral disease, (xiii) presence of
dental disease, (xiv) epicardial fat volume, (xv) cardiac function
(ejection fraction), (xvi) stress echocardiogram test results,
(xvii) characteristics of the aortic geometry (e.g.,
cross-sectional area profile along the ascending and descending
aorta, and surface area and volume of the aorta, (xviii) a SYNTAX
score, as described in U.S. patent application Ser. No. 13/656,183,
filed by Timothy A. Fonte et al. on Oct. 19, 2012, the entire
disclosure of which is incorporated herein by reference, (xix)
plaque burden of existing plaque, (xx) adverse plaque
characteristics of existing plaque (e.g., presence of positive
remodeling, presence of low attenuation plaque, presence of spotty
calcification), (xxi) characteristics of the coronary branch
geometry, (xxii) characteristics of coronary cross-sectional area,
(xxiii) characteristics of coronary lumen intensity, e.g.,
intensity change along the centerline (slope of linearly-fitted
intensity variation), (xxiv) characteristics of surface of coronary
geometry, e.g., 3D surface curvature of geometry (Gaussian,
maximum, minimum, mean), (xxv) characteristics of volume of
coronary geometry, e.g., ratio of total coronary volume compared to
myocardial volume, (xxvi) characteristics of coronary centerline,
(xxvii) characteristics of coronary deformation, (xxviii)
characteristics of existing plaque, and (xxix) characteristics of
coronary hemodynamics derived from computational flow dynamics or
invasive measurement.
[0043] In one embodiment, the characteristics of the coronary
branch geometry may include one or more of: (1) total number of
vessel bifurcations, and the number of upstream/downstream vessel
bifurcations; (2) average, minimum, and maximum upstream/downstream
cross-sectional areas; (3) distances (along the vessel centerline)
to the centerline point of minimum and maximum upstream/downstream
cross-sectional areas, (4) cross-sectional area of and distance
(along the vessel centerline) to the nearest upstream/downstream
vessel bifurcation, (5) cross-sectional area of and distance (along
the vessel centerline) to the nearest coronary outlet and aortic
inlet/outlet, (6) cross-sectional areas and distances (along the
vessel centerline) to the downstream coronary outlets with the
smallest/largest cross-sectional areas, and/or (7)
upstream/downstream volumes of the coronary vessels.
[0044] In one embodiment, the characteristics of coronary
cross-sectional area may include one or more of: (1)
cross-sectional lumen area along the coronary centerline, (2)
cross-sectional lumen area to the power of N (where N can be
determined from various source of scaling laws such as Murray's law
(N=1.5) and Uylings' study (N=1.165.about.1.5)), (3) a ratio of
lumen cross-sectional area with respect to the main ostia (LM, RCA)
(e.g., measure of cross-sectional area at the LM ostium, normalized
cross-sectional area of the left coronary by LM ostium area,
measure of cross-sectional area at the RCA ostium, normalized
cross-sectional area of the right coronary by RCA ostium area), (4)
ratio of lumen cross-sectional area with respect to the main ostia
to the power of N (where N can be determined from various sources
of scaling laws such as Murray's law (N=1.5) and Uyling's study
(N=1.165.about.1.5)), (5) degree of tapering in cross-sectional
lumen area along the centerline (based on a sample centerline
points within a certain interval (e.g., twice the diameter of the
vessel) and computation of a slope of linearly-fitted
cross-sectional area), (6) location of stenotic lesions (based on
detecting minima of cross-sectional area curve (e.g., detecting
locations, where first derivative of area curve is zero and second
derivative is positive, and smoothing cross-sectional area profile
to avoid detecting artifactual peaks), and computing distance
(parametric arc length of centerline) from the main ostium, (7)
length of stenotic lesions (computed based on the proximal and
distal locations from the stenotic lesion, where cross-sectional
area is recovered), (8) degree of stenotic lesions, by evaluating
degree of stenosis based on reference values of smoothed
cross-sectional area profile using Fourier smoothing or kernel
regression, (9) location and number of lesions corresponding to
50%, 75%, 90% area reduction, (10) distance from stenotic lesion to
the main ostia, and/or (11) irregularity (or circularity) of
cross-sectional lumen boundary.
[0045] In one embodiment, the characteristics of coronary
centerline may include: (1) curvature (bending) of coronary
centerline, such as by computing Frenet curvature, based on
.kappa. = p ' .times. p '' p ' 3 , ##EQU00006##
where p is a coordinate of the centerline, and computing an inverse
of the radius of a circumscribed circle along the centerline
points, and (2) tortuosity (non-planarity) of coronary centerline,
such as by computing Frenet torsion, based on
.tau. = ( p ' .times. p '' ) p ''' p ' .times. p '' 2 ,
##EQU00007##
where p is a coordinate of the centerline.
[0046] In one embodiment, calculation of the characteristics of
coronary deformation may involve multi-phase CCTA (e.g., diastole
and systole), including (1) distensibility of coronary artery over
cardiac cycle, (2) bifurcation angle change over cardiac cycle,
and/or (3) curvature change over cardiac cycle. In one embodiment,
the characteristics of existing plaque may be calculated based on:
(1) volume of plaque, (2) intensity of plaque, (3) type of plaque
(calcified, non-calcified), (4) distance from the plaque location
to ostium (LM or RCA), and (5) distance from the plaque location to
the nearest downstream/upstream bifurcation.
[0047] In one embodiment, the characteristics of coronary
hemodynamics may be derived from computational flow dynamics or
invasive measurement. For example, pulsatile flow simulation may be
performed to obtain transient characteristics of blood, by using a
lumped parameter coronary vascular model for downstream
vasculatures, inflow boundary condition with coupling a lumped
parameter heart model and a closed loop model to describe the
intramyocardial pressure variation resulting from the interactions
between the heart and arterial system during cardiac cycle. For
example, the calculation may include: measured FFR, coronary flow
reserve, pressure distribution, FFRct, mean wall-shear stress,
oscillatory shear index, particle residence time, turbulent kinetic
energy, Reynolds number, Womersley number, and/or local flow
rate.
[0048] Method 400 may then include associating the feature vector
with the presence or absence of plaque at each point of the
patient-specific geometric model (step 416). Method 400 may involve
continuing to perform the above steps 412, 414, 416, for each of a
plurality of points in the patient-specific geometric model (step
418), and for each of any number of patients on which a machine
learning algorithm may be based (step 420). Method 400 may then
include training the machine learning algorithm to predict the
probability of the presence of plaque at the points from the
feature vectors at the points (step 422). Examples of machine
learning algorithms suitable for performing this task may include
support vector machines (SVMs), multi-layer perceptrons (MLPs),
and/or multivariate regression (MVR) (e.g., weighted linear or
logistic regression).
[0049] Method 400 may then include storing or otherwise saving the
results of the machine learning algorithm (e.g., feature weights)
to a digital representation, such as the memory or digital storage
(e.g., hard drive, network drive) of a computational device, such
as a computer, laptop, DSP, server, etc. of server systems 106
(step 424).
[0050] FIG. 4B is a block diagram of an exemplary method 450 for
using a machine learning system trained according to method 400
(e.g., a machine learning system 310 executed on server systems
106) for predicting, for a particular patient, the location of
coronary lesions from vessel geometry, physiology, and
hemodynamics, according to an exemplary embodiment of the present
disclosure. In one embodiment, method 450 may include, for one or
more patients (step 452), obtaining a patient-specific geometric
model of a portion of the patient's vasculature (step 454),
obtaining one or more estimates of physiological or phenotypic
parameters of the patient (step 456), and obtaining one or more
estimates of biophysical hemodynamic characteristics of the patient
(step 458).
[0051] Specifically, the step of obtaining a patient-specific
geometric model of a portion of the patient's vasculature (step
454) may include obtaining a patient-specific model of the geometry
for one or more of the patient's blood vessels, myocardium, aorta,
valves, plaques, and/or chambers. In one embodiment, this geometry
may be represented as a list of points in space (possibly with a
list of neighbors for each point) in which the space can be mapped
to spatial units between points (e.g., millimeters). In one
embodiment, this model may be derived by performing a cardiac CT
imaging of the patient in the end diastole phase of the cardiac
cycle. This image then may be segmented manually or automatically
to identify voxels belonging to the aorta and the lumen of the
coronary arteries. Inaccuracies in the geometry extracted
automatically may be corrected by a human observer who compares the
extracted geometry with the images and makes corrections as needed.
Once the voxels are identified, the geometric model can be derived
(e.g., using marching cubes).
[0052] In one embodiment, the step of obtaining one or more
estimates of physiological or phenotypic parameters of the patient
(step 456) may include obtaining a list of one or more estimates of
physiological or phenotypic parameters of the patient, such as
blood pressure, blood viscosity, in vitro blood test results (e.g.,
LDL/Triglyceride cholesterol level), patient age, patient gender,
the mass of the supplied tissue, etc. These parameters may be
global (e.g., blood pressure) or local (e.g., estimated density of
the vessel wall at a location). In one embodiment, the
physiological or phenotypic parameters may include, blood pressure,
hematocrit level, patient age, patient gender, myocardial mass
(e.g., derived by segmenting the myocardium in the image, and
calculating the volume in the image and using an estimated density
of 1.05 g/mL to estimate the myocardial mass), general risk factors
of coronary artery disease (e.g., smoking, diabetes, hypertension,
abdominal obesity, dietary habits, family history, etc.), and/or in
vitro blood test results (e.g., LDL, Triglyceride cholesterol
level).
[0053] In one embodiment, the step of obtaining one or more
estimates of biophysical hemodynamic characteristics of the patient
(step 458) may include obtaining a list of one or more estimates of
biophysical hemodynamic characteristics from computational fluid
dynamics analysis, such as wall-shear stress, oscillatory shear
index, particle residence time, Reynolds number, Womersley number,
local flow rate, and turbulent kinetic energy, etc. Specifically,
the mean wall-shear stress, may be defined as
1 T 1 - T 0 .intg. T 0 T 1 t s t t s , ##EQU00008##
which may be the wall shear stress vector defined as the in-plane
component of the surface traction vector. The oscillatory shear
index (OSI), may be defined as
1 2 ( 1 - 1 T 1 - T 0 .intg. T 0 T 1 t s t 1 T 1 - T 0 .intg. T 0 T
1 t s t ) , ##EQU00009##
which may be a measure of the uni-directionality of shear stress.
The particle residence time may be a measure of the time it takes
blood to be flushed from a specified fluid domain. The turbulent
kinetic energy (TKE) may be a measure of the intensity of
turbulence associated with eddies in turbulent flow, and may be
characterized by measured root-mean-square velocity fluctuation,
and may be normalized by kinetic energy. The Reynolds number may be
defined as
.rho. UD .mu. ##EQU00010##
where (.rho.: density of blood, U: average flow velocity, D: vessel
diameter, .mu.: dynamic viscosity). The Womersley number may be
defined as
D 2 .omega. _ .rho. .mu. ##EQU00011##
where ( .omega.: angular frequency, equal to
1 cardiac cycle length ) . ##EQU00012##
Method 450 may include, for every point in the patient-specific
geometric model of the patient (step 460), creating for that point
a feature vector comprising a numerical description of the geometry
and biophysical hemodynamic characteristic at that point, and
estimates of physiological or phenotypic parameters of the patient
(step 462). Global physiological or phenotypic parameters may be
used in the feature vector of one or more points, and local
physiological or phenotypic parameters may change in the feature
vector of different points. Method 450 may involve continuing to
perform the above steps 460, 462, for each of a plurality of points
in the patient-specific geometric model (step 464).
[0054] Method 450 may then include producing estimates of the
probability of the presence or absence of plaque at each point in
the patient-specific geometric model based on the stored machine
learning results (stored at B, FIG. 4A) (step 468). Specifically,
method 450 may use the saved results of the machine learning
algorithm 310 produced in the training mode of method 400 (e.g.,
feature weights) to produce estimates of the probability of the
presence of plaque at each point in the patient-specific geometric
model (e.g., by generating plaque estimates as a function of the
feature vector at each point). These estimates may be produced
using the same machine learning algorithm technique used in the
training mode (e.g., the SVM, MLP, MVR technique). In one
embodiment, the estimates may be a probability of the existence of
plaque at each point of a geometric model. If there is no existing
plaque at a point, the method may include generating an estimated
probability of the onset of plaque (e.g., lipid-rich, non-calcified
plaque). If plaque does exist at a point, the method may include
generating an estimated probability of progression of the
identified plaque to a different stage (e.g., fibrotic or
calcified), and the amount or shape of such progression. In one
embodiment, the estimates may be a probability of a shape, type,
composition, size, growth, and/or shrinkage of plaque at any given
location or combination of locations. For example, in one
embodiment, (in the absence of longitudinal training data) the
progression of plaque may be predicted by determining that the
patient appears that they should have disease characteristic X
based on the patient's population, despite actually having
characteristic Y. Therefore, the estimate may include a prediction
that the patient will progress from state X to state Y, which may
include assumptions and/or predictions about plaque growth,
shrinkage, change of type, change of composition, change of shape,
etc.). Method 450 may then include saving the estimates of the
probability of the presence or absence of plaque (step 470), such
as to the memory or digital storage (e.g., hard drive, network
drive) of a computational device, such as a computer, laptop, DSP,
server, etc., of server systems 106, and communicating these
patient-specific and location-specific predicted probabilities of
lesion formation to a health care provider, such as over electronic
network 101.
[0055] FIG. 5A is a block diagram of an exemplary method 500 for
training a machine learning system (e.g., a machine learning system
310 executed on server systems 106) for predicting the onset or
change (e.g., growth and/or shrinkage), of coronary lesions over
time, such as by using longitudinal data (i.e., corresponding data
taken from the same patients at different points in time) of vessel
geometry, physiology, and hemodynamics, according to an exemplary
embodiment of the present disclosure. Specifically, method 500 may
include, for one or more patients (step 502), obtaining a
patient-specific geometric model of a portion of the patient's
vasculature (step 504), obtaining one or more estimates of
physiological or phenotypic parameters of the patient (step 506),
and obtaining one or more estimates of biophysical hemodynamic
characteristics of the patient (step 508).
[0056] For example, the step of obtaining a patient-specific
geometric model of a portion of the patient's vasculature (step
504) may include obtaining a patient-specific model of the geometry
for one or more of the patient's blood vessels, myocardium, aorta,
valves, plaques, and/or chambers. In one embodiment, this geometry
may be represented as a list of points in space (possibly with a
list of neighbors for each point) in which the space can be mapped
to spatial units between points (e.g., millimeters). In one
embodiment, this model may be derived by performing a cardiac CT
imaging of the patient in the end diastole phase of the cardiac
cycle. This image then may be segmented manually or automatically
to identify voxels belonging to the aorta and the lumen of the
coronary arteries. Inaccuracies in the geometry extracted
automatically may be corrected by a human observer who compares the
extracted geometry with the images and makes corrections as needed.
Once the voxels are identified, the geometric model can be derived
(e.g., using marching cubes).
[0057] The step of obtaining one or more estimates of physiological
or phenotypic parameters of the patient (step 506) may include
obtaining a list of one or more estimates of physiological or
phenotypic parameters of the patient, such as blood pressure, blood
viscosity, in vitro blood test results (e.g., LDL/Triglyceride
cholesterol level), patient age, patient gender, the mass of the
supplied tissue, etc. These parameters may be global (e.g., blood
pressure) or local (e.g., estimated density of the vessel wall at a
location). In one embodiment, the physiological or phenotypic
parameters may include, blood pressure, hematocrit level, patient
age, patient gender, myocardial mass (e.g., derived by segmenting
the myocardium in the image, and calculating the volume in the
image and using an estimated density of 1.05 g/mL to estimate the
myocardial mass), general risk factors of coronary artery disease
(e.g., smoking, diabetes, hypertension, abdominal obesity, dietary
habits, family history, etc.), and/or in vitro blood test results
(e.g., LDL, Triglyceride cholesterol level).
[0058] The step of obtaining one or more estimates of biophysical
hemodynamic characteristics of the patient (step 508) may include
obtaining a list of one or more estimates of biophysical
hemodynamic characteristics from computational fluid dynamics
analysis, such as wall-shear stress, oscillatory shear index,
particle residence time, Reynolds number, Womersley number, local
flow rate, and turbulent kinetic energy, etc. Specifically, the
mean wall-shear stress, may be defined as
1 T 1 - T 0 .intg. T 0 T 1 t s .fwdarw. t . ##EQU00013##
{right arrow over (t.sub.s)}, which may be the wall shear stress
vector defined as the in-plane component of the surface traction
vector. The oscillatory shear index (OSI), may be defined as
1 2 ( 1 - 1 T 1 - T 0 .intg. T 0 T 1 t s .fwdarw. t 1 T 1 - T 0
.intg. T 0 T 1 t s .fwdarw. t ) , ##EQU00014##
which may be a measure of the uni-directionality of shear stress.
The particle residence time may be a measure of the time it takes
blood to be flushed from a specified fluid domain. The turbulent
kinetic energy (TKE) may be a measure of the intensity of
turbulence associated with eddies in turbulent flow, and may be
characterized by measured root-mean-square velocity fluctuation,
and may be normalized by kinetic energy. The Reynolds number may be
defined as
.rho. UD .mu. ##EQU00015##
where (.rho.: density of blood, U: average flow velocity, D: vessel
diameter, .mu.: dynamic viscosity). The Womersley number may be
defined as
D 2 .omega. _ .rho. .mu. ##EQU00016##
where ( .omega.: angular frequency, equal to
1 cardiac cycle length ) . ##EQU00017##
[0059] Method 500 may further include obtaining an indication of
the growth, shrinkage, or onset of plaque at one or more locations
of the patient-specific geometric model (step 510). For example, in
one embodiment, the location of plaque may be determined using CT
and/or other imaging modalities, including intravascular
ultrasound, or optical coherence tomography. If plaque exists at a
location, method 500 may include obtaining a list of one or more
measurements of coronary plaque composition, burden and
location.
[0060] In order to synchronize geometry obtained from patients over
time, it may be desirable to determine point correspondence between
multiple time variant scans of each individual. In other words, it
may be desirable to learn the vessel characteristics in a location
at the earlier time point that are correlated with the progression
of disease in the same location at the later time point, such as by
using a database of pairs of images of the same patient at two
different time points. Given the image of a new patient, training
data of local disease progression may then be used to predict the
change in disease at each location. Accordingly, in one embodiment,
step 510 may further include: (i) determining a mapping of a
coronary centerline from an initial scan to a follow-up scan; and
(ii) determining a mapping of extracted plaques using curvilinear
coordinates defined along the centerline. In one embodiment, the
coronary centerline mapping may be determined by (i) extracting
centerlines of major epicardial coronary arteries (e.g., left
descending coronary artery, circumlex artery, right coronary
artery) and branch vessels (e.g, diagonal, marginal, etc) for each
scan; (ii) using bifurcating points as fiducial landmarks to
determine common material points between the scans; and (iii) for
points between bifurcations, using linear interpolation or
cross-sectional area profile (e.g., value, slope) of coronary
vessels to identify correspondence. In one embodiment, the mapping
of extracted plaques may be determined by: (i) extracting plaque
from each scan; (ii) parameterizing the location of plaque voxels
by curvilinear coordinate system for each associated centerline
(r,.theta.,s); and determining correspondence of plaque voxels in
each curvilinear coordinate system. In one embodiment, the
curvilinear coordinate system may be defined where:
[0061] r=distance from plaque voxel to the associated centerline
(projection of plaque);
[0062] s=distance from ostium point (Left main or right coronary)
to the projection of plaque voxel onto associated centerline;
and
[0063] .theta.=angular position with respect to reference parallel
path to centerline.
[0064] Method 500 may further include, for each of a plurality of
points in the patient-specific geometric model for which there is
information about the growth, shrinkage, or onset of plaque (step
512), creating a feature vector for the point (step 514) and
associating the feature vector with the growth, shrinkage, or onset
of plaque at that point (step 516). In one embodiment, the step of
creating a feature vector for the point may include creating a
feature vector for that point that consists of a numerical
description of the geometry and biophysical hemodynamic
characteristics at that point, and estimates of physiological or
phenotypic parameters of the patient. For example, a feature vector
for attributes: hematocrit, plaque burden, plaque Hounsfield unit,
distance to ostium, wall shear stress, flow, Reynolds number, and
centerline curvature may be in the form of: (45%, 20 mm.sup.3, 130
HU, 60.5 mm, 70 dyne/cm.sup.2, 1500 mm.sup.3/sec, 400, 1
mm.sup.-1). Global physiological or phenotypic parameters may be
used in the feature vector of all points, and local physiological
or phenotypic parameters may change in the feature vector of
different points.
[0065] In one embodiment, an exemplary feature vector generated in
step 514 may include one or more of: (i) systolic and diastolic
blood pressure, (ii) heart rate, (iii) blood properties including:
plasma, red blood cells (erythrocytes), hematocrit, white blood
cells (leukocytes) and platelets (thrombocytes), viscosity, yield
stress, etc. (iv) patient age, gender, height, weight, etc., (v)
lifestyle characteristics, e.g., presence or absence of current
medications/drugs, (vi) general risk factors of CAD, such as
smoking, diabetes, hypertension, abdominal obesity, dietary habits,
family history of CAD, etc., (vii) in vitro blood test results,
such as LDL, Triglyceride cholesterol level, etc., (viii) coronary
calcium score, (ix) amount of calcium in aorta and valve, (x)
presence of aortic aneurysm, (xi) presence of valvular heart
disease, (xii) presence of peripheral disease, (xiii) presence of
dental disease, (xiv) epicardial fat volume, (xv) cardiac function
(ejection fraction), (xvi) stress echocardiogram test results,
(xvii) characteristics of the aortic geometry (e.g.,
cross-sectional area profile along the ascending and descending
aorta, and Surface area and volume of the aorta, (xviii) a SYNTAX
score, as described above, (xix) plaque burden of existing plaque,
(xx) adverse plaque characteristics of existing plaque (e.g.,
presence of positive remodeling, presence of low attenuation
plaque, presence of spotty calcification), (xxi) characteristics of
the coronary branch geometry, (xxii) characteristics of coronary
cross-sectional area, (xxiii) characteristics of coronary lumen
intensity, e.g., intensity change along the centerline (slope of
linearly-fitted intensity variation), (xxiv) characteristics of
surface of coronary geometry, e.g., 3D surface curvature of
geometry (Gaussian, maximum, minimum, mean), (xxv) characteristics
of volume of coronary geometry, e.g., ratio of total coronary
volume compared to myocardial volume, (xxvi) characteristics of
coronary centerline, (xxvii) characteristics of coronary
deformation, (xxviii) characteristics of existing plaque, and/or
(xxix) characteristics of coronary hemodynamics derived from
computational flow dynamics or invasive measurement.
[0066] In one embodiment, the characteristics of the coronary
branch geometry may include one or more of: (1) total number of
vessel bifurcations, and the number of upstream/downstream vessel
bifurcations; (2) average, minimum, and maximum upstream/downstream
cross-sectional areas; (3) distances (along the vessel centerline)
to the centerline point of minimum and maximum upstream/downstream
cross-sectional areas, (4) cross-sectional area of and distance
(along the vessel centerline) to the nearest upstream/downstream
vessel bifurcation, (5) cross-sectional area of and distance (along
the vessel centerline) to the nearest coronary outlet and aortic
inlet/outlet, (6) cross-sectional areas and distances (along the
vessel centerline) to the downstream coronary outlets with the
smallest/largest cross-sectional areas, and/or (7)
upstream/downstream volumes of the coronary vessels.
[0067] In one embodiment, the characteristics of coronary
cross-sectional area may include one or more of: (1)
cross-sectional lumen area along the coronary centerline, (2)
cross-sectional lumen area to the power of N (where N can be
determined from various source of scaling laws such as Murray's law
(N=1.5) and Uylings' study (N=1.165.about.1.5)), (3) a ratio of
lumen cross-sectional area with respect to the main ostia (LM, RCA)
(e.g., measure of cross-sectional area at the LM ostium, normalized
cross-sectional area of the left coronary by LM ostium area,
measure of cross-sectional area at the RCA ostium, normalized
cross-sectional area of the right coronary by RCA ostium area, (4)
ratio of lumen cross-sectional area with respect to the main ostia
to the power of N (where power can be determined from various
source of scaling laws such as Murray's law (N=1.5) and Uylings'
study (N=1.165.about.1.5)), (5) degree of tapering in
cross-sectional lumen area along the centerline (based on a sample
centerline points within a certain interval (e.g., twice the
diameter of the vessel) and compute a slope of linearly-fitted
cross-sectional area), (6) location of stenotic lesions (based on
detecting minima of cross-sectional area curve (e.g., detecting
locations, where first derivative of area curve is zero and second
derivative is positive, and smoothing cross-sectional area profile
to avoid detecting artifactual peaks), and computing distance
(parametric arc length of centerline) from the main ostium, (7)
length of stenotic lesions (computed based on the proximal and
distal locations from the stenotic lesion, where cross-sectional
area is recovered, (8) degree of stenotic lesions, by evaluating
degree of stenosis based on reference values of smoothed
cross-sectional area profile using Fourier smoothing or kernel
regression, (9) location and number of lesions corresponding to
50%, 75%, 90% area reduction, (10) distance from stenotic lesion to
the main ostia, and/or (11) irregularity (or circularity) of
cross-sectional lumen boundary.
[0068] In one embodiment, the characteristics of coronary
centerline may include: (1) curvature (bending) of coronary
centerline, such as by computing Frenet curvature, based on
.kappa. = p ' .times. p '' p ' 3 , ##EQU00018##
where p is a coordinate of the centerline, and computing an inverse
of the radius of a circumscribed circle along the centerline
points, and/or (2) tortuosity (non-planarity) of coronary
centerline, such as by computing Frenet torsion, based on
.tau. = ( p ' .times. p '' ) p ''' p ' .times. p '' 2 ,
##EQU00019##
where p is a coordinate of the centerline.
[0069] In one embodiment, calculation of the characteristics of
coronary deformation may involve multi-phase CCTA (e.g., diastole
and systole), including (1) distensibility of coronary artery over
cardiac cycle, (2) bifurcation angle change over cardiac cycle,
and/or (3) curvature change over cardiac cycle. In one embodiment,
the characteristics of existing plaque may be calculated based on:
(1) volume of plaque, (2) intensity of plaque, (3) type of plaque
(calcified, non-calcified), (4) distance from the plaque location
to ostium (LM or RCA), and/or (5) distance from the plaque location
to the nearest downstream/upstream bifurcation.
[0070] In one embodiment, the characteristics of coronary
hemodynamics may be derived from computational flow dynamics or
invasive measurement. For example, pulsatile flow simulation may be
performed to obtain transient characteristics of blood, by using a
lumped parameter coronary vascular model for downstream
vasculatures, inflow boundary condition with coupling a lumped
parameter heart model and a closed loop model to describe the
intramyocardial pressure variation resulting from the interactions
between the heart and arterial system during cardiac cycle. For
example, the calculation may include one or more of: measured FFR,
coronary flow reserve, pressure distribution, FFRct, mean
wall-shear stress, oscillatory shear index, particle residence
time, turbulent kinetic energy, Reynolds number, Womersley number,
and/or local flow rate.
[0071] Method 500 may then include associating the feature vector
with the growth, shrinkage, or onset of plaque at each point of the
patient-specific geometric model (step 516). Method 500 may involve
continuing to perform the above steps 512, 514, 516, for each of a
plurality of points in the patient-specific geometric model (step
518), and for each of any number of patients for which a machine
learning algorithm may be based (step 520). Method 500 may also
involve continuing to perform the above steps 512, 514, 516, for
each of a plurality of points in the patient-specific geometric
model, and for each of any number of patients for which a machine
learning algorithm may be based, across any additional time period
or periods useful for generating information about the growth,
shrinkage, or onset of plaque (i.e., the change and/or rate of
change of plaque at each point of the model) (step 522).
[0072] Method 500 may then include training a machine learning
algorithm to predict the probability of amounts of growth,
shrinkage, or onset of plaque at the points from the feature
vectors at the points (step 524). Examples of machine learning
algorithms suitable for performing this task may include support
vector machines (SVMs), multi-layer perceptrons (MLPs), and/or
multivariate regression (MVR) (e.g., weighted linear or logistic
regression). In one embodiment, if training data causes the machine
learning algorithm to predict a lower amount (e.g., size or extent)
of plaque than what is detected, then the machine learning
algorithm may be interpreted as predicting plaque shrinkage; if
training data causes the machine learning algorithm to predict a
higher amount (e.g., size or extent) of plaque than what is
detected, then the machine learning algorithm may be interpreted as
predicting plaque growth.
[0073] Method 500 may then include storing or otherwise saving the
results of the machine learning algorithm (e.g., feature weights)
to a digital representation, such as the memory or digital storage
(e.g., hard drive, network drive) of a computational device, such
as a computer, laptop, DSP, server, etc. of server systems 106
(step 526).
[0074] FIG. 5B is a block diagram of an exemplary method of using
the machine learning system (e.g., machine learning system 310
executed on server systems 106) for predicting, for a particular
patient, the rate of onset, growth/shrinkage, of coronary lesions
from vessel geometry, physiology, and hemodynamics, according to an
exemplary embodiment of the present disclosure. In one embodiment,
method 550 may include, for one or more patients (step 552),
obtaining a patient-specific geometric model of a portion of the
patient's vasculature (step 554), obtaining one or more estimates
of physiological or phenotypic parameters of the patient (step
556), and obtaining one or more estimates of biophysical
hemodynamic characteristics of the patient (step 558).
[0075] Specifically, the step of obtaining a patient-specific
geometric model of a portion of the patient's vasculature (step
554) may include obtaining a patient-specific model of the geometry
for one or more of the patient's blood vessels, myocardium, aorta,
valves, plaques, and/or chambers. In one embodiment, this geometry
may be represented as a list of points in space (possibly with a
list of neighbors for each point) in which the space can be mapped
to spatial units between points (e.g., millimeters). In one
embodiment, this model may be derived by performing a cardiac CT
imaging of the patient in the end diastole phase of the cardiac
cycle. This image then may be segmented manually or automatically
to identify voxels belonging to the aorta and the lumen of the
coronary arteries. Inaccuracies in the geometry extracted
automatically may be corrected by a human observer who compares the
extracted geometry with the images and makes corrections as needed.
Once the voxels are identified, the geometric model can be derived
(e.g., using marching cubes).
[0076] In one embodiment, the step of obtaining one or more
estimates of physiological or phenotypic parameters of the patient
(step 556) may include obtaining a list of one or more estimates of
physiological or phenotypic parameters of the patient, such as
blood pressure, blood viscosity, in vitro blood test results (e.g.,
LDL/Triglyceride cholesterol level), patient age, patient gender,
the mass of the supplied tissue, etc. These parameters may be
global (e.g., blood pressure) or local (e.g., estimated density of
the vessel wall at a location). In one embodiment, the
physiological or phenotypic parameters may include, blood pressure,
hematocrit level, patient age, patient gender, myocardial mass
(e.g., derived by segmenting the myocardium in the image, and
calculating the volume in the image and using an estimated density
of 1.05 g/mL to estimate the myocardial mass), general risk factors
of coronary artery disease (e.g., smoking, diabetes, hypertension,
abdominal obesity, dietary habits, family history, etc.), and/or in
vitro blood test results (e.g., LDL, Triglyceride cholesterol
level).
[0077] In one embodiment, the step of obtaining one or more
estimates of biophysical hemodynamic characteristics of the patient
(step 558) may include obtaining a list of one or more estimates of
biophysical hemodynamic characteristics from computational fluid
dynamics analysis, such as wall-shear stress, oscillatory shear
index, particle residence time, Reynolds number, Womersley number,
local flow rate, and turbulent kinetic energy, etc. Specifically,
the mean wall-shear stress, may be defined as
1 T 1 - T 0 .intg. T 0 T 1 t s .fwdarw. t t s .fwdarw. ,
##EQU00020##
which may be the wall shear stress vector defined as the in-plane
component of the surface traction vector. The oscillatory shear
index (OSI), may be defined as
1 2 ( 1 - 1 T 1 - T 0 .intg. T 0 T 1 t s .fwdarw. t 1 T 1 - T 0
.intg. T 0 T 1 t s .fwdarw. t ) , ##EQU00021##
which may be a measure of the uni-directionality of shear stress.
The particle residence time may be a measure of the time it takes
blood to be flushed from a specified fluid domain. The turbulent
kinetic energy (TKE) may be a measure of the intensity of
turbulence associated with eddies in turbulent flow, and may be
characterized by measured root-mean-square velocity fluctuation,
and may be normalized by kinetic energy. The Reynolds number may be
defined as
.rho. UD .mu. ##EQU00022##
where (.rho.: density of blood, U: average flow velocity, D: vessel
diameter, .mu.: dynamic viscosity). The Womersley number may be
defined as
D 2 .omega. _ .rho. .mu. ##EQU00023##
where ( .omega.: angular frequency, equal to
1 cardiac cycle length ) . ##EQU00024##
[0078] Method 550 may include, for every point in the
patient-specific geometric model (step 560), creating for that
point a feature vector comprising a numerical description of the
geometry and biophysical hemodynamic characteristic at that point,
and estimates of physiological or phenotypic parameters of the
patient. Global physiological or phenotypic parameters can be used
in the feature vector of all points and local physiological or
phenotypic parameters can change in the feature vector of different
points. Method 550 may involve continuing to perform the above
steps 560, 562, for each of a plurality of points in the
patient-specific geometric model (step 564).
[0079] Method 550 may then include producing estimates of the
probability and/or rate of the growth, shrinkage, or onset of
plaque at each point in the patient-specific geometric model based
on the stored machine learning results (stored at B, FIG. 5A) (step
566). Specifically, method 550 may use the saved results of the
machine learning algorithm produced in the training mode of method
500 (e.g., feature weights) to produce estimates of the probability
of growth, shrinkage, or onset (e.g., rates of growth/shrinkage) of
plaque at each point in the patient-specific geometric model (e.g.,
by generating plaque estimates as a function of the feature vector
at each point). These estimates may be produced using the same
machine learning algorithm technique used in the training mode
(e.g., the SVM, MLP, MVR technique). Method 550 may then include
saving the estimates of the probability of the growth, shrinkage,
or onset of plaque (step 568), such as to the memory or digital
storage (e.g., hard drive, network drive) of a computational
device, such as a computer, laptop, DSP, server, etc., of server
systems 106, and communicating these patient-specific and
location-specific predicted probabilities of lesion formation to a
health care provider.
[0080] FIG. 6 is a simplified block diagram of an exemplary
computer system 600 in which embodiments of the present disclosure
may be implemented, for example as any of the physician devices or
servers 102, third party devices or servers 104, and server systems
106. A platform for a server 600, for example, may include a data
communication interface for packet data communication 660. The
platform may also include a central processing unit (CPU) 620, in
the form of one or more processors, for executing program
instructions. The platform typically includes an internal
communication bus 610, program storage and data storage for various
data files to be processed and/or communicated by the platform such
as ROM 630 and RAM 640, although the server 600 often receives
programming and data via a communications network (not shown). The
hardware elements, operating systems and programming languages of
such equipment are conventional in nature, and it is presumed that
those skilled in the art are adequately familiar therewith. The
server 600 also may include input and output ports 650 to connect
with input and output devices such as keyboards, mice,
touchscreens, monitors, displays, etc. Of course, the various
server functions may be implemented in a distributed fashion on a
number of similar platforms, to distribute the processing load.
Alternatively, the servers may be implemented by appropriate
programming of one computer hardware platform.
[0081] As described above, the computer system 600 may include any
type or combination of computing systems, such as handheld devices,
personal computers, servers, clustered computing machines, and/or
cloud computing systems. In one embodiment, the computer system 600
may be an assembly of hardware, including a memory, a central
processing unit ("CPU"), and/or optionally a user interface. The
memory may include any type of RAM or ROM embodied in a physical
storage medium, such as magnetic storage including floppy disk,
hard disk, or magnetic tape; semiconductor storage such as solid
state disk (SSD) or flash memory; optical disc storage; or
magneto-optical disc storage. The CPU may include one or more
processors for processing data according to instructions stored in
the memory. The functions of the processor may be provided by a
single dedicated processor or by a plurality of processors.
Moreover, the processor may include, without limitation, digital
signal processor (DSP) hardware, or any other hardware capable of
executing software. The user interface may include any type or
combination of input/output devices, such as a display monitor,
touchpad, touchscreen, microphone, camera, keyboard, and/or
mouse.
[0082] Program aspects of the technology may be thought of as
"products" or "articles of manufacture" typically in the form of
executable code and/or associated data that is carried on or
embodied in a type of machine readable medium. "Storage" type media
include any or all of the tangible memory of the computers,
processors or the like, or associated modules thereof, such as
various semiconductor memories, tape drives, disk drives and the
like, which may provide non-transitory storage at any time for the
software programming. All or portions of the software may at times
be communicated through the Internet or various other
telecommunication networks. Such communications, for example, may
enable loading of the software from one computer or processor into
another, for example, from a management server or host computer of
the mobile communication network into the computer platform of a
server and/or from a server to the mobile device. Thus, another
type of media that may bear the software elements includes optical,
electrical and electromagnetic waves, such as used across physical
interfaces between local devices, through wired and optical
landline networks and over various air-links. The physical elements
that carry such waves, such as wired or wireless links, optical
links or the like, also may be considered as media bearing the
software. As used herein, unless restricted to non-transitory,
tangible "storage" media, terms, such as computer or machine
"readable medium" refer to any medium that participates in
providing instructions to a processor for execution.
[0083] Other embodiments of the disclosure will be apparent to
those skilled in the art from consideration of the specification
and practice of the invention disclosed herein. It is intended that
the specification and examples be considered as exemplary only,
with a true scope and spirit of the invention being indicated by
the following claims.
* * * * *