U.S. patent application number 15/277672 was filed with the patent office on 2017-01-19 for intrinsic frequency hemodynamic waveform analysis.
The applicant listed for this patent is CALIFORNIA INSTITUTE OF TECHNOLOGY. Invention is credited to Morteza Gharib, Thomas Yizhao Hou, Niema Pahlevan, Peyman Tavallali.
Application Number | 20170014039 15/277672 |
Document ID | / |
Family ID | 48669577 |
Filed Date | 2017-01-19 |
United States Patent
Application |
20170014039 |
Kind Code |
A1 |
Pahlevan; Niema ; et
al. |
January 19, 2017 |
INTRINSIC FREQUENCY HEMODYNAMIC WAVEFORM ANALYSIS
Abstract
Hardware and software methodology are described for cardiac
health measurement. Hemodynamic waveforms variously acquired for a
subject are analyzed to calculate or approximate intrinsic
frequencies in two domains in two domains across the Dicrotic
Notch. The intrinsic frequencies provide metrics/ measures that
correlate to the cardiac health of the subject. The systems may be
used for monitoring a condition and/or is diagnosis. Exemplary uses
include identifying (diagnosing) the presence of arrhythmia, heat
failure, atrial fibrillation, aneurysms, vessel stenosis or aortic
valve dysfunction and the necessity for valve replacement and/or
monitoring congestive heart failure progression, together with
identifying the acute need for hospitalization in connection with
daily testing for any such condition.
Inventors: |
Pahlevan; Niema; (Pasadena,
CA) ; Tavallali; Peyman; (Pasadena, CA) ; Hou;
Thomas Yizhao; (Arcadia, CA) ; Gharib; Morteza;
(Altadena, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CALIFORNIA INSTITUTE OF TECHNOLOGY |
Pasadena |
CA |
US |
|
|
Family ID: |
48669577 |
Appl. No.: |
15/277672 |
Filed: |
September 27, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14684662 |
Apr 13, 2015 |
9462953 |
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15277672 |
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13725039 |
Dec 21, 2012 |
9026193 |
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14684662 |
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61739880 |
Dec 20, 2012 |
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61717008 |
Oct 22, 2012 |
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61579456 |
Dec 22, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/0077 20130101;
A61B 5/02028 20130101; A61B 5/02438 20130101; A61B 5/0013 20130101;
A61B 8/5223 20130101; A61B 8/06 20130101; A61B 5/02405 20130101;
A61B 5/7282 20130101; A61B 5/7278 20130101; A61B 8/565 20130101;
A61B 5/7235 20130101; A61B 5/0507 20130101; A61B 5/0004 20130101;
A61B 5/746 20130101; A61B 8/02 20130101; A61B 5/02416 20130101 |
International
Class: |
A61B 5/024 20060101
A61B005/024; A61B 5/00 20060101 A61B005/00 |
Claims
1. A system for acquiring and analyzing a hemodynamic waveform of a
subject, the system comprising: an optical scanner, the scanner
adapted to capture a signal corresponding to a hemodynamic
waveform; and at least one computer processor connected to the
scanner by a wired or wireless connection, wherein the computer
processor is adapted to receive the signal for the hemodynamic
waveform, determine a Dicrotic Notch using the signal, calculate
first and second intrinsic frequencies (.omega..sub.1,
.omega..sub.2) on each side of the Dicrotic Notch for the waveform,
and output a signal corresponding to intrinsic frequencies
results.
2. A computer-implemented method of analyzing a signal, comprising:
inputting a hemodynamic waveform data for a subject, the waveform
including a Dicrotic Notch; determining a position of the Dicrotic
Notch in the waveform for dividing the signal into first and second
sections for analysis; analyzing each of the first and second
sections of the waves by to determine first and second intrinsic
frequencies (.omega..sub.1, .omega..sub.2) where each intrinsic
frequency is at or about a frequency that carries the highest
energy for all frequencies of an instantaneous frequency curve; and
outputting a result of the analyzing.
Description
RELATED APPLICATIONS
[0001] This filing is a continuation application of U.S. patent
application Ser. No. 14/684,662, filed Apr. 13, 2015, which is a
continuation application of U.S. patent application Ser. No.
13/725,039, filed Dec. 21, 2012, now U.S. Pat. No. 9,026,193, which
claims the benefit of U.S. Provisional Application No. 61/579,456,
filed Dec. 22, 2011, U.S. Provisional Application No. 61/717,008,
filed Oct. 22, 2012, and U.S. Provisional Application No.
61/739,880, filed Dec. 20, 2012, all of which are incorporated by
reference herein in their entireties.
FIELD
[0002] This filing relates to hemodynamic waveform analysis.
BACKGROUND
[0003] Cardiovascular diseases (CVDs) are the underlying cause of
about one of every three deaths in United States each year.
Likewise, about 34% of American adults are suffering from one or
more types of CVD. In 2010, the total direct and indirect cost of
CVDs was approximately $503 billion.
[0004] Certainly, there is an urgent need to develop new methods
and devices for diagnosing and monitoring CVDs. Diagnosis enables
early intervention and remediation. Monitoring may be a useful tool
in each of behavior modification and prediction/avoidance of an
acute event leading to emergency hospitalization, morbidity and/or
mortality. New methods and devices to meet these need(s)
advantageously employ noninvasive measurements to reduce medical
complications and increase patient comfort. Ideally, they are also
easy to use by medical personnel and subjects in a home
environment.
SUMMARY
[0005] The inventive embodiments include devices and systems (e.g.,
including the sensor hardware referenced herein and the addition of
a computer processor and other ancillary/support electronics and
various housing elements) and methods (including the hardware and
software for carrying out the same) meeting some or all of the
aforementioned needs. Such methods and devices are adapted for
analysis of the hemodynamic waveform.
[0006] This waveform derives from the pulsatile pumping mechanism
of the heart. The pumping of blood sends pressure and flow waves
into the compliant aorta and vascular network. Pressure and flow
waves generated by the heart propagate in the compliant arterial
vasculature. These waves get reflected at various reflection sites
existing in the arterial system. The intensity and pulsatility of
this pressure and resulting dilation wave decreases as the waves
enter smaller vessels and eventually disappear in the capillary
bed. Therefore, wave dynamics dominate the hemodynamics of large
vessels such as the ascending, descending, and abdominal aorta.
[0007] These waves carry information about the health or disease
state of the heart, vascular system and/or coupling of heart and
vasculature. As a result, extracting information from these waves
offers the opportunity to make determinations about health or
disease conditions that are of great importance.
[0008] A healthy heart operates based on a delicate balance between
its pumping characteristics (cardiac output, stroke volume) and
wave dynamics of the vascular system. This delicate balance can be
impaired due to aging, smoking, or disease conditions such as high
blood pressure, heart failure, or type-2 diabetes. The analysis
devices, systems, and methods herein enable diagnosing, or grading
such conditions in terms of severity and/or monitoring a subject's
condition.
[0009] The subject devices, systems, and methods employ computer
analysis of a waveform based on instantaneous/intrinsic frequency
theory to provide an index/metric that enables detection of an
impaired balance between the heart and aorta at different ages and
under various disease conditions. The devices, systems, and methods
involve evaluating frequencies of the pressure wave, wall
displacement wave or velocity/flow wave (generally: hemodynamic
waves) for various detection and monitoring applications. The
intrinsic (or dominant) frequencies of a hemodynamic waveform are
preferably determined over two or more temporal domains.
[0010] At least two of these domains correspond to before and after
closing of the aortic valve as apparent in the graph of aortic
pressure throughout the cardiac cycle. This graph displays a small
dip (the "incisure" or "Dicrotic Notch") in any of the waveforms.
Further, devices, systems, methods of detecting the Dicrotic Notch
are provided that are useful especially in connection with subjects
that suffer valve dysfunction and, thus, limited closure of the
valve.
[0011] The intrinsic frequencies (also optionally referred to as
the dominant frequencies) of the hemodynamic waveform correspond to
the frequency that carries the highest energy (or power) among all
frequencies in a specific time interval the instantaneous
frequency. The subject devices, systems and methods include means
for directly calculating these values. They also include means of
estimating the dominant frequencies (intrinsic frequencies) as
elaborated upon below.
[0012] However determined in the embodiments hereof, only the shape
of the hemodynamic waves (an uncalibrated waveform) are needed for
determining the intrinsic/dominant frequencies for each part of the
waveform. Magnitude of the hemodynamic wave(s) is not required. As
such, noninvasive hardware and methodology such as ultrasound,
echocardiography and cardiac microwave can be used for
measurements. Moreover, a need for measurement system calibration
is avoided. Thus, tonomeric type sensor hardware is also easily
employed as are optical and other sensor devices--any of which type
scanner may be used to provide a hemodynamic waveform input signal
for the subject devices, systems, and methods.
[0013] However, the hardware is configured, in an acute setting
(whether with a primary care physician or a specialist) systems
running software according to the subject methodology may be used
to detect atrial fibrillation or aortic valve dysfunction and the
need for surgical intervention. Alternatively, such devices may be
employed for monitoring (daily at home or periodically with a
primary care physician) as part of long-term care in connection
with medicating for hypertension or monitoring congestive heart
failure (CHF). By observing changes in hemodynamic waveform status,
the embodiments may also be useful for predicting the type of
events leading to or requiring hospitalization.
[0014] Moreover, variations of the devices, systems, and methods
herein, where intrinsic frequency of a given waveform is
determined, enables a range of other applications. These include
diagnosing diastolic dysfunction, atrial fibrillation, low cardiac
output, aortic insufficiency or approximating stroke volume, the
risk of coronary artery disease, prediction of restenosis after
coronary stent placement (all through the pressure or vessel wall
displacement waveform) or diagnosing mitral regurgitation through
the velocity waveform.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The figures provided herein illustrate examples and
embodiments and may be diagrammatic and not necessarily drawn to
scale, with some components and features exaggerated and/or
abstracted for clarity. Variations from the embodiments pictured
are contemplated. Accordingly, depiction of aspects and elements in
the figures are not intended to limit the scope of the claims,
except when such intent is explicitly stated.
[0016] FIGS. 1A and 1B diagrammatically illustrate the dynamic
coupling of the heart and aorta in a human circulatory system.
[0017] FIGS. 2A and 2B illustrate example embodiments of the
systems described herein.
[0018] FIGS. 3A and 3B illustrate the pressure waveforms of two
young adults and their calculated IF values; FIGS. 4A-4C illustrate
the pressure waveforms of three 30-40 year old adults and their
calculated IF values; and FIGS. 5A and 5B illustrate the pressure
waveforms of an aged adult and another with severe heart failure,
respectively, with their calculated IF values.
[0019] FIG. 6A plots trends in hemodynamic waveform IF; FIG. 6B
plots the difference in the FIG. 6A IF values.
[0020] FIG. 7 is a table presenting possible diagnoses associated
with the subject IF values.
[0021] FIG. 8 is a process flowchart illustrating various method
options hereof.
[0022] FIGS. 9A and 9B illustrate the characteristic change in
contours in pressure wave and flow wave between the ascending aorta
and the saphenous artery, respectively.
[0023] FIG. 10A is an example of a modeled pressure waveform; FIG.
10B illustrates instantaneous waveform frequency associated
therewith.
[0024] FIG. 11A is an example of a pressure waveform of a subject
whose dicrotic notch is not easily distinguishable from the
pressure waveform; FIG. 11B illustrates the second derivative of
the waveform.
[0025] FIGS. 12A-12C and 13A-13C are panels illustrating the
hemodynamic analysis of quantified models.
[0026] FIGS. 14A-14C illustrate the pressure waveform of three
blind test examples.
DETAILED DESCRIPTION
[0027] Various example embodiments are described below. Reference
is made to these examples in a non-limiting sense. They are
provided to illustrate more broadly applicable aspects of inventive
aspects. Various changes may be made to the embodiments described
and equivalents may be substituted without departing from their
true spirit and scope. In addition, many modifications may be made
to adapt a particular situation, material, composition of matter,
process, process act(s) or step(s) to the objective(s), spirit or
scope of the claims made herein.
[0028] That said, the present subject matter is based on the fact
that a healthy heart-aorta system in the human body represents a
delicate coupling between heart pumping characteristics and aortic
(arterial) wave dynamics. This optimum coupling becomes impaired by
arterial diseases (e.g., arterial stiffening, aging, hypertension),
heart diseases (e.g., heart failure, coronary diseases) or other
negative contributors (e.g., smoking).
[0029] FIG. 1A illustrates a coupled heart-aorta system 10 in
systole, with the aortic valve open (not shown) and blood being
pumped by the heart 12 into the aorta 14. As such, the heart and
aorta construct a coupled dynamic system before the closure of the
aortic valve. As shown in FIG. 1B, after the valve closure during
diastole, the heart and aortic systems are decoupled in a second
system state 10'. The aortic waves contain in each state include
information about heart dynamics, arterial network dynamic and
heart-aorta coupling.
[0030] Extraction of such information by analysis as described in
further detail herein is based on intrinsic (instantaneous)
frequency and includes devices, systems, and methods for: [0031]
diagnosis of different CVDs from a pressure waveform; [0032]
evaluation of the severity of CVD from a pressure waveform; [0033]
diagnosis of different CVD from a wall displacement waveform;
[0034] evaluation of the severity of CVD from a wall displacement
waveform; [0035] diagnosis of different CVDs from a flow waveform;
[0036] evaluation of the severity of CVD from a flow waveform;
[0037] diagnosis of different CVDs from a combination of pressure,
wall [0038] displacement, and/or flow waveform; and [0039]
evaluation of the severity of CVD form combination of pressure,
wall displacement and/or flow waveform. Traditional methods of data
analysis are based on the assumption of data being stationary and
linear. Fourier analysis is just a typical, and often used, method.
However, it is a known fact that the stationarity and linearity
assumptions do not hold for arterial waves. Yet, a new method of
Sparse Time-Frequency Representation (STFR) has been developed that
may be applied herein to achieve the above, and still other methods
and goals.
[0040] The STFR method is employed because it is well suited for
nonlinear data analysis, it is less sensitive to noise perturbation
and, more importantly, it preserves some intrinsic physical
property of the signal. The general STFR problem is defined as
follows:
[0041] Minimize M
Subject to: s(t)=.SIGMA..sub.i=1.sup.Ma.sub.i(t)cos
.theta..sub.i(t), a.sub.i(t)cos .theta..sub.i(t).di-elect cons.D,
(i=1, . . . , M)
In the subject devices, systems, and methods, a simplified and
modified version of STFR may be employed by minimizing:
f ( t ) - a 1 X ( 0 , T 0 ) Cos .omega. 1 t - b 1 X ( 0 , T 0 ) Sin
.omega. 1 t - a 2 X ( T 0 , T ) Cos .omega. 2 t - b 2 X ( T 0 , T )
Sin .omega. 2 t 2 2 X = ( a , b ) = { 1 .alpha. .ltoreq. t .ltoreq.
b 0 otherwise Subject to : { q 1 Cos .omega. 1 T 0 + b 1 Sin
.omega. 1 T 0 = a 2 Cos .omega. 2 T 0 + b 2 Sin .omega. 2 T 0 a 1 =
a 2 Cos .omega. 2 T + b 2 Sin .omega. 2 T ( 2 ) ##EQU00001##
where, T.sub.0 is the time of aortic valve closure (i.e., the
charted Dicrotic Notch) in order to determine intrinsic/dominant
frequency (IF) values (.omega..sub.1, .omega..sub.2) in the two
domains on either side of the Dicrotic Notch.
[0042] Still, it is to be recognized that the IF values can be
approximated and still fall within the spirit and scope of the
subject embodiments. In one example, the IF values are approximated
using the graph of the instantaneous frequency (.theta..sub.1(t))
of method of equation (1). Possible indices that can be used to
approximate .omega..sub.1 and .omega..sub.2 as such include: [0043]
.omega..sub.1 approximating .omega..sub.1 by averaging the
.theta..sub.1(t) over an specific time period before the
.theta..sub.1(t) transition (when the aortic valve is open); [0044]
.omega..sub.2 approximating .omega..sub.2 by averaging the
.theta..sub.1(t) over an specific time period after the
.theta..sub.1(t) transition (when the aortic valve is closed);
[0045] .omega..sub.1 approximating .omega..sub.1 by averaging the
maximum and minimum value of .theta..sub.1(t) curve before the
.theta..sub.1(t) transition (when the aortic valve is open); [0046]
.omega..sub.2 approximating .omega..sub.2 by averaging the maximum
and minimum value of .theta..sub.1(t) curve after the
.theta..sub.1(t) transition (when the aortic valve is closed);
[0047] .omega..sub.1.sup.max approximating .omega..sub.1 using the
one of the local maximum of .theta..sub.1(t) curve before the
.theta..sub.1(t) transition (when the aortic valve is open); [0048]
.omega..sub.1.sup.min approximating .omega..sub.1 using the one of
the local minimum of .theta..sub.1(t) curve before the
.theta..sub.1(t) transition (when the aortic valve is open); [0049]
.omega..sub.2.sup.max approximating .omega..sub.1 using the one of
the local maximum of .theta..sub.1(t) curve after the
.theta..sub.1(t) transition (when the aortic valve is closed); and
[0050] .omega..sub.2.sup.min approximating .omega..sub.1 using the
one of the local minimum of .theta..sub.1(t) curve after the
.theta..sub.1(t) transition (when the aortic valve is closed).
Likewise, it is possible to calculate or approximate IF by other
known time-frequency analyses such as Empirical Mode Decomposition
(EMO) methods (see U.S. Pat. No. 6,738,734 to Huang, incorporated
herein by reference in its entirety) and Wavelet methods.
[0051] As evident, any/all such calculation either for directly
calculating IF values or approximating them requires the use of a
computer processor. As discussed further below, FIGS. 3A-5B
illustrate pressure waveforms for which .omega..sub.1,
.omega..sub.2 IF values have been calculated. These calculations
took computer-scanned values from printed published pressure
waveform data and processed such data with a general purpose
computer processor.
[0052] FIGS. 2A and 2B illustrate example systems that are capable
of acquiring such waveform information and/or processing the same.
The IF results based on the same may be produced and/or displayed
in real time for physician evaluation and/or logged for monitoring
or subsequent evaluation of a physician or other analysis.
Alternatively, diagnosis based on the IF results may be displayed,
alarms triggered, etc. for users who are not either medically or
specially trained (e.g., as in the case of home use or general
practice physicians.) Regardless, what is meant by "real time" in
the context above will generally mean that it takes about 1 second
or less from the time of data acquisition for calculation and data
presentation, more often such action is essentially without delay.
In any case, real time activity in the subject embodiments concerns
manipulation of such a mass of data and calculations that the task
is well beyond practicable human capacity, thereby requiring the
use of a computer processor.
[0053] In any case, FIG. 2A diagrammatically illustrates a
computer-based system 100 in which a scanner 110 includes on-board
electronics for sending and receiving signals 112 to acquire
hemodynamic waveform measurements. Use of a microwave sensor (at
least for measuring vessel displacement) and/or ultrasound sensors
(for measuring either or both vessel distension and blood
velocity/flow) for such purposes is well known. An example of
suitable publicly-available hardware includes that employed in the
GE LOGIQ Book Portable Ultrasound Machine, which technology is
readily adapted to the subject devices, systems, and methods.
Suitable microwave sensor technology is described in Fletcher, R R,
and S Kulkarni, "Clip-on wireless wearable microwave sensor for
ambulatory cardiac monitoring," IEEE, 2010. 365-369. Web. 3
February 2012.
[0054] Other types of scanners may be used as well. These include
tonomeric and optical units. In the former case, the tonomeric
sensor will include a force or pressure sensing transducer
producing an electronic signal corresponding to a pressure or
wall--displacement based hemodynamic waveform. The optical scanner
may embody any of a variety of technologies in producing a signal
that correlates to a hemodynamic waveform. In one embodiment, the
optical scanner may include infrared (IR) diode(s) and sensor(s)
suitable for measuring a wall displacement waveform. In another
embodiment, the scanner operates as a camera. In which case
(whether in a flat-bed scanner format, in typical stand-alone
digital camera format, or incorporated in the bezel of a iPAD or
the like), such a device is able to capture a printed or otherwise
displayed hemodynamic waveform and convert it to a digital
representation employing a CCD, CMOS or the like. Then, a computer
program such as the UN-SCAN-IT Graph Digitizer can be employed to
produce a signal representative of the captured hemodynamic
waveform to be received by a computer processor for analysis.
[0055] Scanner 110 may be hand-held for scanning a seated or
standing patient 90 as shown. Or the scanner hardware may be
incorporated in a C-arm or tunnel for scanning a patient lying
down.
[0056] A hand-held scanner may advantageously be battery-powered so
as to avoid connection to a wall socket. Whether hand-held or
incorporated or in a larger unity, scanner 110 may interface by
wireless (as indicated) or wired (not shown) communication with a
general purpose computer 120, optionally including display 122 to
perform and communicate results, respectively. Otherwise, on-board
processing and/or display hardware may be provided in connection
with the sensor housing itself. Such options may be especially
useful for a hand-held or semi-portable device as these may be used
by a patient/subject at home, during travel, etc.
[0057] Notably, all the hardware may be located in one location.
Alternatively, the computer system may be located at a remote
location as in a "Cloud" based option. Further, the system may
consist of the computer and its programming without a sensor means.
In which case, the system may include an optical scanner or other
camera means for image or other electronic capture of a waveform
produced by another (already available) measurement machine (e.g.,
the aforementioned GE scanner, etc.).
[0058] As yet another option, FIG. 2B, illustrates a portable
system 100'. It includes a tablet-style computer device 124 (e.g.,
an iPAD) with an integral display 122. A tonomeric or optical
scanner sensor probe 110' is shown connected to computer 124 via a
bus 126 and wired connection 128. However, the scanner (of whatever
type) may be wirelessly connected as in the previous example as
well. Alternatively, the scanner employed in capturing the
hemodynamic waveform may be the camera 110'' integrated in the
device.
[0059] Regardless of how the hemodynamic waveforms are acquired, a
given waveform 0 is analyzed in the subject method to produce two
IF values. Per FIG. 3A, these correspond (exactly or approximately)
to .omega..sub.1 and .omega..sub.2 for a first section/domain 1 in
which the heart and aorta are in a coupled system 10 and a second
section/domain 2 for the aorta in a system 10' alone. These domains
are separated/delineated by the Dicrotic Notch (DN) as shown.
[0060] FIG. 3A also shows a scale for the pressure measure of the
waveform. However, as commented upon, the scale of the waveform is
not important--merely its shape. More notable are the .omega..sub.1
and .omega..sub.2 values determined from FIGS. 3A-5B.
[0061] Accordingly, FIGS. 3A and 3B illustrate the pressure
waveforms of two young adults and their calculated IF values. The
data are from young healthy adults when heart+aorta system and
arterial wave dynamics are on their optimum condition (or close to
optimum). The IF values are close to each other. FIGS. 4A-4C
illustrate the pressure waveforms of three 30-40 year old adults
and their calculated IF values. The data are from adults when
heart+aorta system and arterial wave dynamics are getting off of
their optimum condition, likely due to increased aortic rigidity.
In these examples, the IF values are further separated than those
from FIGS. 3A and 3B. FIGS. 5A and 5B illustrate the pressure
waveforms of an aged adult and another with severe heart failure,
respectively, with their calculated IF values. The difference
between the IF values is considerably larger.
[0062] FIG. 6A illustrates plotted trends in calculated IF for the
first and second waveform domains. Even with the limited data set,
it is clear that wl either stays relatively constant or increases
with age while 0)2 decreases with age. Thus, in the plot of FIG. 6B
showing difference between IF values, the difference increases with
age.
[0063] Similarly, based on the observation of known conditions for
a variety of subjects and their associated IF waveform values, it
is possible to develop a database and propose correlations between
the IF values and cardiac health/CVD conditions. Such an effort is
represented in the table of FIG. 7. Here, relative (> or <)
.omega..sub.1, .omega..sub.2 and .DELTA..omega. values are
tabulated as indicative of various possible conditions. Backed by
appropriate study power, such a table may be provided as an aid to
physicians interpreting IF analysis output from a system 100/100'.
Alternatively, the relations/logic for the table may be embedded in
programming such a system to offer diagnosis independent of
physician feedback/interpretation.
[0064] In any case, FIG. 8 is an example of a computer program
flowchart 200 illustrating general and specific processes that may
be carried out according to the subject methods. At 202 hemodynamic
waveform data is acquired and/or input in electronic format. At 204
the waveform date is optionally segmented at the position of the
Dicrotic Notch. This may be a process as discussed further below,
or inherent to 206 where IF values are calculated. The computer
process may then terminate with the output (by graphic display,
printout, etc.) of .omega..sub.1, .omega..sub.2 and .DELTA..omega.
for physician evaluation. Otherwise the computer program at 208 may
interrogate and compare the IF values with a database of values
characteristic of health; based on this comparison, at 210 the
program can offer a diagnosis of CVD and assess the associated
risk. Alternatively or additionally, at 212 the process may proceed
to compare the current IF values with a database containing
historical IF values for the patient, with subsequent evaluation of
CVD risk factor and/or disease progression determination at 214.
Following any such evaluation, at 216 the program may suggest
associated therapy, preventive stratagem or the like--including
prompting immediate hospitalization if the onset of a cardiac event
is detected.
[0065] Regarding the input or acquired waveform, it may be taken at
any of a selected arterial site. FIGS. 9A and 9B illustrate the
characteristic change in contours in pressure wave and flow wave
between the ascending aorta and the saphenous artery, respectively.
Either type of wave at any of the locations may be employed.
However, it may sometimes be advantageous to take the measurements
close to the location associated with the corresponding disease
(e.g., close to the heart for heart diseases)
[0066] FIG. 10A is an example of a pressure waveform from a
computational model of the aorta. The computational model was
physiologically relevant. The methods, as well as the physical
parameters of the model, are described in Pahlevan N M, Gharib M.
"Aortic wave dynamics and its influence on left ventricular
workload," PLoS ONE. 2011;6:e23106 incorporated herein by reference
in its entirety and discussed further below. Relevant to the
present discussion, however, FIG. 10B illustrates the calculated
instantaneous waveform frequency 3 from the waveform of FIG. 10A.
Notably, the instantaneous frequency in each of domain 1 and 2 is
oscillating around certain dominant frequencies in two range bands
A and B. The system IF values fall within these bands. As noted
above, the IF values can be calculated or estimated within these
bands.
[0067] Moreover, as alluded to above, the shape of the
instantaneous frequency waveform may be employed to determine the
position of the Dicrotic Notch (DN) where the waveform changes the
oscillation range as shown. Another approach to identifying the
Dicrotic Notch is presented in connection with FIGS. 11A and 11B.
In FIG. 11A, a waveform 0 is provided for a subject whose dicrotic
notch is not easily distinguishable from pressure waves (patients
with severe valve diseases usually fall in this category). Thus
there is very little noticeable indication of aortic valve closure.
However, a second derivative plotting 4 of the original waveform 0
yields a sharp peak indicative of the Dicrotic Notch. Finding DN by
either approach may constitute a sub-process within flowchart
element 204.
EXAMPLES
[0068] Various additional examples are provided herein. A first set
of examples is presented in connection with FIGS. 12A-12C and
13A-13C, which relate the underpinnings of the subject IF values.
The second set of examples presented in connection with FIGS.
14A-14C were the subject of a blind study where diagnosis was
attempted for patients that had otherwise been
physician-tested.
Model Examples
[0069] Regarding the first examples, these represent work with a
computational model of the aorta. Full details of the computational
model are as cited above. So-configured, simulations were performed
for different levels of aortic rigidities labeled E.sub.1 through
E.sub.7, where E.sub.1 is the aortic rigidity of a 30-year old
healthy individual. All the other E; are multiplicative factor of
E.sub.1 as: E.sub.2=1.25E.sub.1, E.sub.3=1.5E.sub.1,
E.sub.4=1.75E.sub.4, E.sub.5=2E.sub.1, E.sub.6=2.5E.sub.1, and
E.sub.7=3E.sub.1. At each Ei, simulations were completed, providing
computed pressure waveforms for eight heart rates (70.5, 75, 89.5,
100, 120, 136.4, 150, and 187.5 beats per minute (bpm)). The
pressure waveforms for E.sub.1-E.sub.3 at 100, 70 and 70 bpm are
shown in FIGS. 13A-13C, respectively. Intrinsic frequencies, were
also computed using equation (2) with results as shown.
[0070] As discussed above, IF values can be estimated from the
instantaneous frequency or can be calculated. Here, in this example
they were calculated for each rigidity at each pulse (bpm) rate.
The results of such are presented for E1-E3 in FIGS. 13A-13C.
[0071] Also discussed above, is the hypothesis based on data
obtained from young, healthy individuals that optimal heart
coupling is present (as indicative of optimal health) when the IF
values (i.e., .omega..sub.1 and .omega..sub.2) are equivalent. If
true, the intersection of the .omega..sub.1 and .omega..sub.2 plots
in FIGS. 13A-13B should yield and be equivalent to the optimal
heart rate. This range is represented in the vertical band across
each graph.
[0072] Most interesting, is that the results of this hypothesis
exactly match the results of another presented in connection with
the model arrived at from another perspective. Namely, in Pahlevan,
et al., optimal heart rate for the model was argued to be when left
ventricular (LV) pulsatile load is minimized. The computationally
determined minimum pulsitile power also shown in FIGS. 13A-13B
occur at the same rate as predicted by the
.omega..sub.1-.omega..sub.2 intersection. As such, additional
corroboration is offered for the use of IF as an indicator of
cardiovascular health (with respect to a stated optimal condition
of zero difference between .omega..sub.1 and .omega..sub.2).
Blind Test Examples
[0073] Further corroboration of the value of IF as a predictive
value of cardiac health is presented in connection with FIGS.
14A-14C. Recorded pressure waveforms were provided and
scanned/digitized. The subject STFR method was then applied to each
and a diagnosis by the inventors hereof of the possible health
condition of the patent was made without consulting the physician
who provided the data and made an independent diagnosis without the
use of IF values. As evident from the below, the IF-predicted
health status offered good agreement with the patient status.
[0074] For the waveform presented in FIG. 14A, with a HR of 79.4
with calculated .omega..sub.1=73.2, .omega..sub.2=52.3 and
.DELTA..omega.=20.9, the following observations were made: [0075]
.omega..sub.1 was less than HR indicating LV dysfunction (severe
abnormality); [0076] .omega..sub.2 was low indicative indicating
mild arterial rigidity (consistent with 35-45 year old male or
55-65 year old female); and [0077] .DELTA..omega. was low
indicating good heart-aorta coupling. In fact, the patient was a
66-year-old female with no history of hypertension, she had a
normal ejection fraction, but presented with atypical chest pain of
indeterminate cause.
[0078] For the waveform presented in FIG. 14A, with a HR of 97.5
with calculated .omega..sub.1=121.4, .omega..sub.2=44 and
.DELTA..omega.=77.4 the following observations were made: [0079]
.omega..sub.1 was high indicating LV dysfunction; [0080]
.omega..sub.2 was very low indicating severe arterial rigidity
(consistent with 60+year-old male); and [0081] .DELTA..omega. was
very high indicating severe out-of-optimum coupling (indicative of
severe arterial rigidity and heart diseases). In fact, the patient
was a 65-year-old male with severe coronary disease; he had very
poor LV function with an ejection fraction of 25%.
[0082] For the waveform presented in FIG. 14A, with a HR of 69.5
with calculated .omega..sub.1=113, .omega..sub.2=31.4 and
.DELTA..omega.=81.6 the following observations were made: [0083]
.omega..sub.1 was not particularly high indicating no severe LV
dysfunction; [0084] .omega..sub.2 was extremely low indicating
aging and arterial disease (consistent with a 60+year-old male);
and [0085] .DELTA..omega. was very high indicating severe out of
optimum coupling (consistent with arterial and heart diseases). In
fact, the patient was a 71-year-old male with coronary disease,
atrial fibrillation and a history of hypertension.
[0086] Variations
[0087] In addition to the embodiments that been disclosed in detail
above, still more are possible within the classes described, and
the inventors intend these to be encompassed within this
specification and claims. This disclosure is intended to be
exemplary, and the claims are intended to cover any modification or
alternative which might be predictable to a person having ordinary
skill in the art.
[0088] Moreover, the various illustrative processes described in
connection with the embodiments herein may be implemented or
performed with a general purpose processor, a Digital Signal
Processor (DSP), an Application Specific Integrated Circuit (ASIC),
a Field Programmable Gate Array (FPGA) or other programmable logic
device, discrete gate or transistor logic, discrete hardware
components, or any combination thereof designed to perform the
functions described herein. A general purpose processor may be a
microprocessor, but in the alternative, the processor may be any
conventional processor, controller, microcontroller, or state
machine. The processor can be part of a computer system that also
has a user interface port that communicates with a user interface,
and which receives commands entered by a user, has at least one
memory (e.g., hard drive or other comparable storage, and random
access memory) that stores electronic information, including a
program that operates under control of the processor and with
communication via the user interface port, and a video output that
produces its output via any kind of video output format, e.g., VGA,
DVI, HDMI, DisplayPort, or any other form.
[0089] A processor may also be implemented as a combination of
computing devices, e.g., a combination of a DSP and a
microprocessor, a plurality of microprocessors, one or more
microprocessors in conjunction with a DSP core, or any other such
configuration. These devices may also be used to select values for
devices as described herein. The camera may be a digital camera of
any type including those using CMOS, CCD or other digital image
capture technology.
[0090] The steps of a method or algorithm described in connection
with the embodiments disclosed herein may be embodied directly in
hardware, in a software module executed by a processor, or in a
combination of the two. A software module may reside in Random
Access Memory (RAM), flash memory, Read Only Memory (ROM),
Electrically Programmable ROM (EPROM), Electrically Erasable
Programmable ROM (EEPROM), registers, hard disk, a removable disk,
a CD-ROM, or any other form of storage medium known in the art. An
exemplary storage medium is coupled to the processor such that the
processor can read information from, and write information to, the
storage medium. In the alternative, the storage medium may be
integral to the processor. The processor and the storage medium may
reside in an ASIC. The ASIC may reside in a user terminal. In the
alternative, the processor and the storage medium may reside as
discrete components in a user terminal.
[0091] In one or more exemplary embodiments, the functions
described may be implemented in hardware, software, firmware, or
any combination thereof. If implemented in software, the functions
may be stored on, transmitted over or resulting in
analysis/calculation data output as one or more instructions, code
or other information on a computer-readable medium.
Computer-readable media includes both computer storage media and
communication media, including any medium that facilitates transfer
of a computer program from one place to another. A storage media
may be any available media that can be accessed by a computer. By
way of example, and not limitation, such computer-readable media
can comprise RAM, ROM, EEPROM, CD-ROM or other optical disk
storage, magnetic disk storage or other magnetic storage devices,
or any other medium that can be used to carry or store desired
program code in the form of instructions or data structures and
that can be accessed by a computer. The memory storage can also be
rotating magnetic hard disk drives, optical disk drives, or flash
memory based storage drives or other such solid state, magnetic, or
optical storage devices. Also, any connection is properly termed a
computer-readable medium. For example, if the software is
transmitted from a website, server, or other remote source using a
coaxial cable, fiber optic cable, twisted pair, digital subscriber
line (DSL), or wireless technologies such as infrared, radio, and
microwave, then the coaxial cable, fiber optic cable, twisted pair,
DSL, or wireless technologies such as infrared, radio, and
microwave are included in the definition of medium. Disk and disc,
as used herein, includes compact disc (CD), laser disc, optical
disc, digital versatile disc (DVD), floppy disk and Blu-ray disc
where disks usually reproduce data magnetically, while discs
reproduce data optically with lasers. Combinations of the above
should also be included within the scope of computer-readable
media.
[0092] Operations as described herein can be carried out on or over
a website. The website can be operated on a server computer, or
operated locally, e.g., by being downloaded to the client computer,
or operated via a server farm. The website can be accessed over a
mobile phone or a PDA, or on any other client. The website can use
HTML code in any form, e.g., MHTML, or XML, and via any form such
as cascading style sheets ("CSS") or other.
[0093] Also, the inventors intend that only those claims which use
the words "means for" are intended to be interpreted under 35 USC
112, sixth paragraph. Moreover, no limitations from the
specification are intended to be read into any claims, unless those
limitations are expressly included in the claims. The computers
described herein may be any kind of computer, either general
purpose, or some specific purpose computer such as a workstation.
The programs may be written in C, or Java, Brew or any other
programming language. The programs may be resident on a storage
medium, e.g., magnetic or optical, e.g. the computer hard drive, a
removable disk or media such as a memory stick or SD media, or
other removable medium. The programs may also be run over a
network, for example, with a server or other machine sending
signals to the local machine, which allows the local machine to
carry out the operations described herein.
[0094] Also, it is contemplated that any optional feature of the
embodiment variations described may be set forth and claimed
independently, or in combination with any one or more of the
features described herein. Reference to a singular item, includes
the possibility that there is a plurality of the same items
present. More specifically, as used herein and in the appended
claims, the singular forms "a," "an," "said," and "the" include
plural referents unless specifically stated otherwise. In other
words, use of the articles allow for "at least one" of the subject
item in the description above as well as the claims below. It is
further noted that the claims may be drafted to exclude any
optional element. As such, this statement is intended to serve as
antecedent basis for use of such exclusive terminology as "solely,"
"only" and the like in connection with the recitation of claim
elements, or use of a "negative" limitation.
[0095] Without the use of such exclusive terminology, the term
"comprising" in the claims shall allow for the inclusion of any
additional element irrespective of whether a given number of
elements are enumerated in the claim, or the addition of a feature
could be regarded as transforming the nature of an element set
forth in the claims. Except as specifically defined herein, all
technical and scientific terms used herein are to be given as broad
a commonly understood meaning as possible while maintaining claim
validity.
[0096] The breadth of the present invention is not to be limited to
the examples provided and/or the subject specification, but rather
only by the scope of the claim language. All references cited are
incorporated by reference in their entirety. Although the foregoing
embodiments been described in detail for purposes of clarity of
understanding, it is contemplated that certain modifications may be
practiced within the scope of the appended claims.
* * * * *