U.S. patent application number 17/729861 was filed with the patent office on 2022-08-11 for hybrid image-invasive-pressure hemodynamic function assessment.
The applicant listed for this patent is OPSENS INC.. Invention is credited to Claude BELLEVILLE.
Application Number | 20220248969 17/729861 |
Document ID | / |
Family ID | 1000006289182 |
Filed Date | 2022-08-11 |
United States Patent
Application |
20220248969 |
Kind Code |
A1 |
BELLEVILLE; Claude |
August 11, 2022 |
HYBRID IMAGE-INVASIVE-PRESSURE HEMODYNAMIC FUNCTION ASSESSMENT
Abstract
There is described a method for calculating a patient-specific
hemodynamic parameter. The method comprises measuring at least one
pressure measurement in an artery using an intravascular pressure
measurement device, and taking at least one medical image of the
artery from a medical imaging instrument, the at least one medical
image of the artery being synchronous with the at least one
pressure measurement. Both the pressure measurement and the medical
image are fed to a computing system to calculate a flow from the at
least one medical image, to calculate parameters of the artery from
at least two artery pressure drops and corresponding flow
components, and based on the flow and the parameters of the artery,
to calculate a patient-specific hemodynamic parameter or a
plurality thereof.
Inventors: |
BELLEVILLE; Claude; (Ville
de Quebec, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OPSENS INC. |
Quebec |
|
CA |
|
|
Family ID: |
1000006289182 |
Appl. No.: |
17/729861 |
Filed: |
April 26, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16963131 |
Jul 17, 2020 |
11369277 |
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PCT/CA2019/050894 |
Jun 27, 2019 |
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17729861 |
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62690756 |
Jun 27, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/6851 20130101;
A61B 5/0275 20130101; A61B 5/0215 20130101 |
International
Class: |
A61B 5/0215 20060101
A61B005/0215; A61B 5/0275 20060101 A61B005/0275; A61B 5/00 20060101
A61B005/00 |
Claims
1. A method executable by a computing system comprising a processor
in communication with an intravascular pressure measurement device
and with a medical imaging instrument, the method comprising:
introducing a radiation-absorbing contrast medium in the artery;
taking, with the medical imaging instrument, at least one medical
image of the artery during propagation of the radiation-absorbing
contrast medium in the artery; feeding the at least one medical
image to the computing system; measuring, by the computing system,
in the at least one medical image, a diameter D of the artery which
varies along a length x of the artery; tracking a propagation of
the radiation-absorbing contrast medium in the artery and measuring
a time taken for a propagation between a first point L.sub.1 to a
second point L.sub.2 in the artery, calculating, by the processor,
a flow from the at least one medical image, by determining a volume
of the artery based on a distance between the first point L.sub.1
and the second point L.sub.2 in the artery and based on the
diameter D of the artery.
2. The method of claim 1, wherein calculating the flow further
comprises dividing the volume of the artery by the time taken for
the contrast agent to propagate between the first point L.sub.1 and
the second point L.sub.2 in the artery.
3. The method of claim 1, wherein the volume is calculated as: V =
( L 2 - L 1 ) 4 .intg. L .times. 1 L .times. 2 .times. .pi.
.function. ( D .function. ( x ) ) 2 .times. d .times. x ,
##EQU00016##
4. The method of claim 1, wherein measuring, in the at least one
medical image defining a plane, the diameter D of the artery which
is perpendicular to the plane of the at least one medical image
comprises using densitometry on the radiation-absorbing contrast
medium to measure D as a function of x by applying Beer-Lambert's
law on a measured intensity in a section of the artery.
5. The method of claim 4, wherein using densitometry on the
radiation-absorbing contrast medium comprises determining a depth
th of artery perpendicular to the plane of the at least one medical
image: th = ln .function. ( I i ) - ln .function. ( I T ) .alpha. ,
##EQU00017## where I.sub.i is the incident radiation intensity,
I.sub.T is the transmitted radiation intensity, and .alpha. is a
constant that corresponds to the contrast agent absorbing
coefficient.
6. A system comprising: a computing system in communication with an
intravascular pressure measurement device and with a medical
imaging instrument, the computing system comprising a memory for
storing instructions and data from both the intravascular pressure
measurement device and the medical imaging instrument, and a
processor which executes the instructions to: receive at least one
pressure measurement from the intravascular pressure measurement
device in an artery; receive at least one aortic pressure from
another pressure device; receive at least one medical image of the
artery from the medical imaging instrument; calculate a flow from
the at least one medical image; calculate parameters of the artery
from at least two artery pressure drops and corresponding flow
components; and based on the flow and the parameters of the artery,
calculate a patient-specific hemodynamic parameter.
7. The system of claim 6, wherein the intravascular pressure
measurement device is a pressure guidewire.
8. The system of claim 6, further comprising the intravascular
pressure measurement device configured to measure the at least one
pressure measurement simultaneously with the at least one medical
image being acquired in real time.
9. The system of claim 6, wherein each of the at least one pressure
measurement has a corresponding synchronous medical image of the
artery.
10. The system of claim 6, wherein the processor is further
configured to: measure, in the at least one medical image, a
diameter D of the artery which varies along a length x of the
artery; track a propagation of a radiation-absorbing contrast
medium in the artery and measure a time taken for a propagation
between a first point L.sub.1 to a second point L.sub.2 in the
artery, wherein calculating the flow comprises dividing a volume V
by the time taken for the propagation to calculate a mean blood
flow in the artery.
11. The system of claim 10, wherein the volume V is determined as:
V = ( L 2 - L 1 ) 4 .intg. L .times. 1 L .times. 2 .times. .pi.
.function. ( D .function. ( x ) ) 2 .times. dx . ##EQU00018##
12. The system of claim 10, wherein the processor, when measuring,
in the at least one medical image defining a plane, the diameter D
of the artery which is perpendicular to the plane of the at least
one medical image is further configured to use densitometry on the
radiation-absorbing contrast medium to measure D as a function of x
by applying Beer-Lambert's law on a measured intensity in a section
of the artery.
13. The system of claim 6, wherein the processor is further
configured to: calculate the flow associated to a hyperemic
condition using the parameters of the artery, wherein calculating
the patient-specific hemodynamic parameter is based on a pressure
drop and the calculated flow associated to the hyperemic condition,
the hyperemic condition being induced using an intracoronary or
intravenous injection of a hyperemic agent in the artery.
14. The system of claim 6, wherein the patient-specific hemodynamic
parameter comprises a microvascular resistance.
15. The system of claim 6, wherein the patient-specific hemodynamic
parameter comprises a coronary flow reserve (CFR).
16. The system of claim 6, wherein the at least one pressure
measurement and the at least one medical image are measured in a
resting condition, first during a systole period which covers at
least a portion of a systole, and second during a diastole period
which covers at least a portion of the diastole, and wherein the
processor is further configured to calculate parameters of the
artery by solving a second-degree equation of the parameters of the
artery using the at least two artery pressure drops and
corresponding flow components which are respectively measured and
calculated in the systole period and in the diastole period.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 16963131 filed Jul. 17, 2020, which is a
national-phase application of international application
PCT/CA2019/050894 filed internationally on Jun. 27, 2019, which
claims benefit or priority of U.S. provisional patent application
62/690,756, filed Jun. 27, 2018, which are hereby incorporated
herein by reference in their entirety.
BACKGROUND
(a) Field
[0002] The subject matter disclosed generally relates to a method
for assessment of hemodynamic function. More specifically, it
relates to a method for determining hemodynamic parameters using an
intravascular pressure measurement device combined with medical
imaging.
(b) Related Prior Art
[0003] Coronary artery diseases are currently diagnosed by
assessing the impact of coronary stenosis on blood flow. A large
number of clinical studies have shown the treatment of coronary
stenosis based on the measurement of Fractional Flow Reserve (FFR)
leads to the improvement of patient outcomes. FFR consists in
taking the ratio of distal pressure (Pd) to proximal pressure (Pa).
In the absence of coronary artery flow restricting lesion, FFR
equals 1. As the blood flow restriction increases, the FFR value
drops. The FFR ratio expresses the percentage of blood flow reserve
in presence of the lesion compared to the same artery without any
lesion. More specifically, it has been shown that deferring the
treatment of a specific stenosis with an FFR value above 0.80,
while treating the stenosis if the FFR value is equal or below
0.80, leads to an improved outcome for the patient.
[0004] Although FFR measures the severity of epicardial stenosis,
the presence of microvascular dysfunction can increase the FFR
value, underestimating the severity of a lesion. Coronary flow
reserve (CFR) depends on both the epicardial and microvascular
resistances. Therefore, discordance between FFR and CFR can occur
in deciding whether a lesion should be treated or not. As both
parameters are known to have prognostic values, the discordance
between FFR and CFR illustrates the need for a refined diagnostic
that would take the microvascular function into consideration
[Bon-Kwon Koo, JACC, Vol. 10, No. 10, 2017]. Despite restoring
normal epicardial flow in most cases of acute myocardial
infarction, there remains a high rate of microvascular obstruction
and myocardial necrosis [Niccoli G et al, J Am Coll Cardiol 2009;
54:281-292]. Elective coronary angioplasty is associated with up to
20% of periprocedural myocardial infarction, believed to be the
result of micro-embolization [Jaffe R et al., JACC Cardiovasc
Intery 2010; 3:695-704]. A significant proportion of patients with
symptoms of stable angina present normal coronary arteries, for
which the alteration in microvessel function is the factor
contributing to the myocardial ischemia [Schwartz L et al., Arch
Intern Med 2001; 161:1825-1833]. In patients with hypertrophic
cardiomyopathy, microvascular dysfunction is a strong predictor of
left ventricular dysfunction and death [Cecchi F et al, N Engl J
Med 2003; 349:1027-1035]. Microvascular resistance was shown to be
associated to left ventricular and clinical outcomes after
ST-segment-elevation. Compared with standard clinical measures of
the efficacy of myocardial reperfusion, including the ischemic
time, ST-segment elevation, angiographic blush grade, and CFR,
microvascular resistance was shown to have superior clinical value
for risk stratification and may be considered a reference test for
failed myocardial reperfusion [Carrick D. et al., Circulation 2016,
134:1833-1847]. Microvascular resistance, not FFR, is the strongest
predictor of improvement of the coronary flow in grey-zone FFR
lesions [Niida T. et al, Catheter Cardiovasc Interv. 2018;1-11]
[0005] Although in recent years the understanding of coronary blood
flow has mainly focused on the epicardial arteries, there is a
growing body of evidence showing that microcirculation plays a key
role in the diagnostic of ischemic patients which could ultimately
lead to the most appropriate myocardial reperfusion treatment
plan.
[0006] However, the measurement of microvascular resistance is not
common practice in today's catheterization laboratory (or cath lab)
as the methods are tricky and clinical workflow is disruptive. The
microvascular resistance is typically calculated by dividing the
distal pressure (Pd) by the flow within the artery. The distal
pressure is commonly measured using a pressure sensitive guidewire.
Various methods exist to measure blood flow. Doppler sensitive
guidewire can be used to measure the velocity of blood. This method
is sub-optimal due to poor wire handling characteristics and due to
blood velocity measurement varying with the pointing direction of
the wire portion comprising the Doppler sensor, which is
operator-dependent and anatomy-dependent. Another method is based
on the time it takes for the blood to reach the distal portion of
the artery by measuring the time difference between the injection
of a bolus of saline and its detection by a temperature sensitive
guidewire located distally, also called thermodilution.
Thermodilution method leads to variable transit time measurement,
requiring multiple bolus of saline injection. It also assumes a
constant artery volume between patients, hence also assuming
minimal coronary disease. Recently, a new method is based on the
measurement of blood mean temperature drop following continuous
infusion of known flow rate of saline at room temperature
[Aarnoudse W. et al., JACC, Vol. 50, NO. 24, 2007]. Although this
last method is believed to be more accurate and reproducible, it
requires the use of a special catheter and set-up that is likely to
add to the procedure time and cost. Except for the Doppler based
method, these methods measure the mean blood flow and therefore,
they don't have the ability to measure time-dependent blood flow
and time-dependent microvascular resistance (i.e., not applicable
in cases in which the blood flow and the resistance are a function
of time instead of being constant).
[0007] In recent years, there has been a lot of work in developing
non-invasive image-based pressure-flow characteristics of coronary
arteries in view of determining the Fractional Flow Reserve without
the need for invasive pressure measurement. Patient-specific
geometry of arteries measured using angiograms, CT-scan, MRI-scan,
and other non-invasive imaging systems known in the art, are at the
center of these non-invasive patient hemodynamic assessment. These
methods involve building a closed-loop model that includes the
contribution, among others, of the artery, the microvascular system
and the heart. The heart and microvascular systems are modelled
with lumped systems of resistance, inductance and capacitance, the
heart also including a blood flow driving force. On the other hand,
the arteries are usually modelled using well known Navier-Stokes
equations, either using 3D computational models, reduced order
computational model, multi-scale models that combine different
types of models depending on specific feature of an artery segment.
An artery can also be modelled using analytical or semi-analytical
models or lumped model where the resistance, inductance and/or
capacitance of the artery, or of a given segment of artery, are
calculated using patient-specific geometry of the artery obtained
from the non-invasive imaging system.
[0008] In order to resolve the closed-loop system and hence
determine the pressure-flow characteristics of the artery, it is
necessary to know the boundary and the initial conditions of the
systems. Because these boundary and initial conditions are not
known for the patient under evaluation, these models use generic
parameters such as mean microvascular resistance, vessel
elasticity, left ventricular contractility, all usually from the
characteristics of general population. These assumptions may lead
to significant errors in calculating the pressure-flow
characteristics of an artery. Among all input parameters necessary
to calculate the pressure-flow characteristics, the microvascular
resistance amounts to 59% of all the errors [Morris et al., JACC.
Vol. 2, No. 4, 2017]. Microvascular resistance variability among
patient has indeed a direct impact on the accuracy of the
pressure-flow characteristics as computed from the closed-loop
model, as it was observed herein above with respect to clinical
results. It is therefore not possible to determine patient specific
microvascular resistance without the use of additional patient
specific measurements.
[0009] U.S. patent application publication No. 2017/0032097,
entitled "Method and system for enhancing image-based blood flow
computations using physiological measurements" uses various
measurements in order to calculate the microvascular resistance. A
first method involves the measurement of the total time of flight
(T.sub.mn) for injected contrast agent to reach the distal portion
of the artery, assumed to be equal to blood flow, and multiplying
this T.sub.mn value by measured distal pressure (Pd) to get a
microvascular resistance. This method assumes a generic mean artery
volume that is not patient specific, therefore not considering
patient disease in the artery. Also, it does not account for any
time dependence of microvascular resistance. Other proposed methods
are based on adding invasive pressure or flow measured values to
various pressure-flow relations, such as 3D Computation Flow
Dynamic (CFD), reduced order CFD, multiscale methods that combine
different pressure-flow relations depending on the feature within
the artery, analytical and semi-analytical methods, lumped model
(resistance, inductance and capacitance model). Measured pressure
or flow value is devoted to improve the accuracy of the model.
However, these methods do not take full advantage of the presence
of an invasive device within the coronary artery as they still rely
to a significant extent on the pressure-flow/artery-geometry
relations.
[0010] There is therefore a need for a system that reliably
measures the microvascular resistance while being fast and easy to
operate such that it is compatible with today's clinical
workflow.
SUMMARY
[0011] According to an aspect of the invention, there is provided a
method comprising: [0012] measuring at least one pressure
measurement in an artery using an intravascular pressure
measurement device; [0013] taking at least one medical image of the
artery from a medical imaging instrument, the at least one medical
image of the artery being synchronous with the at least one
pressure measurement; [0014] feeding both the at least one pressure
measurement and the at least one medical image to a computing
system; [0015] calculating a flow from the at least one medical
image; [0016] calculating parameters of the artery from at least
two artery pressure drops and corresponding flow components; and
[0017] based on the flow and the parameters of the artery,
calculating a patient-specific hemodynamic parameter.
[0018] According to an embodiment, the steps of measuring the at
least one pressure measurement and taking the at least one medical
image are performed in two conditions of blood flow, wherein
calculating parameters of the artery comprises solving a
second-degree equation of the parameters of the artery using the at
least two artery pressure drops and corresponding flow components
which are measured in the two conditions of blood flow
[0019] According to an embodiment, the two conditions of blood flow
comprise a higher blood flow condition and a lower blood flow
condition, the method further comprising administering an agent to
cause higher blood flow condition prior to said steps of measuring
the at least one pressure measurement and taking the at least one
medical image under the higher blood flow condition.
[0020] According to an embodiment, the higher blood flow condition
is induced by injection of contrast agent or hyperemic agent to
induce partial or full hyperemia.
[0021] According to an embodiment, there is further provided the
step of producing a sound signal when inducing the higher blood
flow condition for timing the step of measuring the at least one
pressure measurement with the injection of a microvascular dilator
agent.
[0022] According to an embodiment, there is further provided the
step of introducing a radiation-absorbing contrast medium in the
artery, wherein taking the at least one medical image of the artery
further comprises: [0023] measuring, in the at least one medical
image, a diameter D of the artery which varies along a length x of
the artery; [0024] tracking a propagation of the
radiation-absorbing contrast medium in the artery and measuring a
time taken for a propagation between a first point L1 to a second
point L2 in the artery, wherein calculating the flow comprises
dividing a volume V,
[0024] V = ( L 2 - L 1 ) 4 .intg. L .times. 1 L .times. 2 .pi.
.function. ( D .function. ( x ) ) 2 .times. d .times. x ,
##EQU00001##
by the time taken for the propagation to calculate a mean blood
flow in the artery.
[0025] According to an embodiment, measuring, in the at least one
medical image defining a plane, a diameter D of the artery which is
perpendicular to the plane of the at least one medical image
comprises using densitometry on the radiation-absorbing contrast
medium to measure D as a function of x by applying Beer-Lambert's
law on a measured intensity in a section of the artery.
[0026] According to an embodiment, there is further provided the
step of inducing hyperemic condition using an intracoronary or
intravenous injection of a hyperemic agent in the artery, and
calculating the flow associated to the hyperemic condition using
the parameters of the artery, wherein calculating the
patient-specific hemodynamic parameter is based on a pressure drop
and the calculated flow associated to the hyperemic condition.
[0027] According to an embodiment, the patient-specific hemodynamic
parameter comprises a microvascular resistance.
[0028] According to an embodiment, the steps of measuring the at
least one pressure measurement and taking the at least one medical
image are performed in a resting condition, first during a systole
period which covers at least a portion of a systole, and second
during a diastole period which covers at least a portion of the
diastole, wherein calculating parameters of the artery comprises
solving a second-degree equation of the parameters of the artery
using the at least two artery pressure drops and corresponding flow
components which are respectively measured and calculated in the
systole period and in the diastole period.
[0029] According to an embodiment, there is further provided the
step of identifying a presence of a stenosis in the artery and
identifying a segment distal from the stenosis which is free of any
stenosis, and taking a plurality of pressure measurements along
said segment.
[0030] According to an embodiment, identifying a presence of a
stenosis comprises comparing one of the parameters of the artery
with a predetermined threshold to identify a presence of a stenosis
in the artery.
[0031] According to an embodiment, identifying a presence of a
stenosis comprises using the at least one medical image to identify
a presence of a stenosis in the artery by determining a presence of
a luminal obstruction above 50%.
[0032] According to an embodiment, taking a plurality of pressure
measurements along said segment is made by providing a tip of the
intravascular pressure measurement device at a most distal location
in said segment and pulling back the intravascular pressure
measurement device.
[0033] According to an embodiment, there is further provided the
step of calculating a geometry-based flow using the plurality of
pressure measurements along said segment and numerically solving
Navier-Stokes equations, and using the geometry-based flow to apply
corrections to the parameters of the artery and to the step of
calculating a flow from the at least one medical image, thereby
applying a correction to the patient-specific hemodynamic parameter
to account for the presence of the stenosis.
[0034] According to an embodiment, measuring the at least one
pressure measurement and taking at least one medical image are
synchronous by simultaneously acquiring the at least one pressure
measurement and the at least one medical image in real time, or by
time stamping the at least one pressure measurement and the at
least one medical image.
[0035] According to another aspect of the invention, there is
provided a system comprising: [0036] a computing system in
communication with an intravascular pressure measurement device and
with a medical imaging instrument, the computing system comprising
a memory for storing instructions and data from both the
intravascular pressure measurement device and the medical imaging
instrument, and a processor which executes the instructions to:
[0037] receive at least one pressure measurement from the
intravascular pressure measurement device in an artery; [0038]
receive at least one aortic pressure from another pressure device;
[0039] receive at least one medical image of the artery from the
medical imaging instrument; [0040] calculate a flow from the at
least one medical image; [0041] calculate parameters of the artery
from at least two artery pressure drops and corresponding flow
components; and [0042] based on the flow and the parameters of the
artery, calculate a patient-specific hemodynamic parameter.
[0043] According to an embodiment, the intravascular pressure
measurement device is a pressure guidewire.
BRIEF DESCRIPTION OF THE DRAWINGS
[0044] Further features and advantages of the present disclosure
will become apparent from the following detailed description, taken
in combination with the appended drawings, in which:
[0045] FIG. 1 is a schematic cross-section view illustrating an
intravascular pressure measurement device taking a pressure
measurement in an artery, according to an embodiment;
[0046] FIG. 2 is a schematic cross-section view illustrating a
modelized artery, according to an embodiment;
[0047] FIG. 3 is a flowchart illustrating a method for determining
hemodynamic parameters with diastolic flow measurements and with a
hyperemic agent, according to an embodiment;
[0048] FIG. 4 is a flowchart illustrating a method for determining
hemodynamic parameters with systolic and diastolic flow
measurements and without any hyperemic agent, according to an
embodiment;
[0049] FIG. 5 is a flowchart illustrating a method for determining
hemodynamic parameters with systolic and diastolic flow
measurements and without any hyperemic agent, with geometric
correction, according to an embodiment;
[0050] FIG. 6 is a schematic cross-section view illustrating an
intravascular pressure measurement device taking a pressure
measurement in an artery having a branch, according to an
embodiment; and
[0051] FIG. 7 is a schematic cross-section view illustrating an
intravascular pressure measurement device taking a pressure
measurement in an artery, with segmentation shown to isolate
different stenoses in different segments, according to an
embodiment.
[0052] It will be noted that throughout the appended drawings, like
features are identified by like reference numerals.
DETAILED DESCRIPTION
[0053] The method according to an embodiment involves the
simultaneous (or synchronous) combination of an invasive pressure
measurement instruments, such as an intravascular pressure
measurement device (e.g., a pressure guidewire) with a non-invasive
instrument such as a medical imaging instrument which takes medical
images of the artery. The method is for determining a blood flow
with greater precision in order to determine other values which
depends on a proper measurement of the blood flow.
[0054] Instead of using non-invasive instruments in replacement of
invasive instruments, as typical in recent prior art methods, and
which involves drawbacks as discussed above, the methods according
to the invention use both together. This combination allows precise
pressure measurements from the intravascular pressure measurement
device and complement those with medical images that personalize
the calculation of hemodynamic parameters with real data, in real
time, on the geometry of the artery and flow data in the artery.
The hemodynamic parameters are thus computed with a higher accuracy
and better reflect the actual and real-time conditions in the
artery than if no geometry or flow data were collected from the
non-invasive instrument as proposed herein.
[0055] An object of the presently described embodiments is to
provide clinical workflow compatible methods, i.e., fast and easy,
that allow measuring or estimating the flow within a target artery,
which along with intravascular pressure measurement allows
calculating hemodynamic parameters such as microvascular
resistance, coronary flow reserve (CFR) and Fractional flow reserve
(FFR). It is also an object of the present embodiments to combine
invasive pressure measurement to coronary artery images, in order
to obtain accurate coronary flow, which when combined with
intravascular pressure measurements, allows the calculation of
hemodynamic parameters.
[0056] FIG. 1 illustrates a typical set-up used to assess the
hemodynamic function of a patient with coronary artery disease
(CAD). Epicardial artery 1 directs blood flow from the ostium 4 of
the artery to the distal end 5, where blood enters the
microvascular system where oxygen exchange occurs. The
microvascular resistance is illustrated herein by a single
resistance R.sub.M. It will be shown later that it is also possible
to model the microvascular system to take into consideration other
physiologic functions such as the myocardium capacitance. In a
typical set-up, a guiding catheter 3 is placed at the ostium of the
artery. The guiding catheter can be used to deliver contrast agent
used to reveal the contour of the artery; to guide medical devices
such as pressure guidewire 2 to the ostium of the artery and
further distal in the coronary artery; to measure blood pressure at
the entry of the artery, herein called the aortic pressure Pa. The
aortic pressure can be used as a boundary condition forcing the
blood to flow within the artery. Distal pressure Pd measured by the
pressure guidewire can also be used as a boundary condition.
[0057] FIG. 2 illustrates a functional equivalent of the vascular
system. The blood flow and pressure at the ostium (i.e., proximal
pressure) can be represented by Q and Pa, respectively. The
epicardial may contain a stenosis that creates a pressure drop
.DELTA.p, leading to distal pressure Pd at the distal end of the
artery. Flow Q is conserved if one assumes there is no significant
branch between the ostium and the distal end. Collateral vessels
(aka collaterals) may also be present in certain patients. When
present, a collateral usually connects to the main vessel at a
distal location relative to the pressure guidewire measuring point
Pd, hence between the Pd point and the microcirculation system. The
collateral contributes additional blood flow to the
microcirculation, hence reducing both the flow and the pressure
drop across the stenosis. Although the flow from the collateral
adds to the epicardial flow, distal pressure before and after the
collateral does not change, this allows taking into consideration
the contribution of collaterals flow in FFR measurement. FFR is
defined by relation 1, where Q.sup.N is the flow in the absence of
stenosis (normal artery), and Q.sup.S is the flow in presence of
the stenosis, both flows obtained under stress condition, i.e.,
under full hyperemic condition (normally induced by a hyperemic
agent such as adenosine). It is reasonable to assume that the flow
is a linear function of the pressure, the microvascular resistance
R.sub.M being the proportional parameter between these quantities,
where flow can be expressed in terms of microvascular pressure
difference and associated resistance R.sub.M. Considering the
microvascular resistance R.sub.M is minimal and does not change
whether there is a stenosis or not and considering the venous
pressure (Pv) is negligible (Pv.apprxeq.0), FFR is obtained from
the last part of relation 1.
F .times. F .times. R = Q N Q S = ( P d - P v ) / R M ( P a - P v )
/ R M .apprxeq. P d P a 1 ##EQU00002##
[0058] Distal pressure measurements obtained from a pressure
guidewire can be associated to the distal position of the artery by
co-registering the pressure with position on the image.
Co-registering means simultaneously measuring and recording both
values. It is also possible to take more than one pressure
measurement along the artery and co-registering more than one
pressure and associated positions on the image. It is furthermore
possible to pull-back the pressure guidewire 2 while recording the
images and co-registering the measured pressure along the artery
with positions on the images that are associated to each of the
pressure measurements. A given pressure measurement can be
localised in the artery by detecting the edge of the tip of the
pressure guidewire 2, where the pressure sensor is located and
where the radio-opacity abruptly changes because of the
radio-opaque tip presumably provided on the tip of the pressure
guidewire 2.
[0059] Prior art systems devoted to combine invasive measurement
with image to either improve accuracy or ease the calculation of a
hemodynamic function are strongly dependent on the geometry of the
acquired images, by computing the pressure-flow characteristics of
the artery from 3-D computational flow dynamic (CFD), reduced order
CFD, 0-D analytical models or other lumped models. All these models
are based on the geometry of the artery to model the pressure-flow
characteristics. It is therefore a purpose of the present
embodiments to develop pressure-flow characteristics less sensitive
to the geometry of the artery to improve the eventual assessment
performed by the measurement instruments (pressure guidewire 2 and
imaging instruments).
[0060] It is understood the embodiments below comprise at least one
computer used to acquire, store, process, displays, transmits or
otherwise indicated herein below to use and measured data. A
computer is understood to be any system that comprises a processing
unit, a memory and required ports of communication to able to
perform logical operations on signals.
Mean Blood Flow Measurement
[0061] A first embodiment is proposed below to measure
artery-specific hemodynamic parameters without the need for a
3-dimensional image re-construction and with minimal dependence on
the local geometry of the artery. A radiation absorbing contrast
medium is introduced at the ostium of the artery. It is possible to
track the propagation of the contrast agent and therefore,
determine the time it takes for the blood to propagate from one
point to another.
[0062] Various prior art methods exist to track this propagation of
the contrast agent, including methods described in U.S. Pat. No.
5,150,292 entitled "Method and system for determination of
instantaneous and average blood flow rates from digital angiograms"
and in U.S. Pat. No. 5,048,534 entitled "Method of and device for
determining quantities characterizing the flow of a liquid in a
vascular system", both incorporated herein by reference. US patent
application US 2017/0032097, also incorporated herein by reference,
uses a similar method to measure the time it takes for the blood to
reach the distal position of the artery. The flow in that prior art
document is then calculated using the same relation as the one used
for measuring the flow by thermodilution, which takes the inverse
of the time to reach the distal end of the artery
(Q.about.1/T.sub.mn). It assumes the volume of the specific
targeted artery is the same as the mean artery volume of a general
population, so it is neither patient-specific nor artery-specific.
Because thermodilution methods that use temperature sensitive
guidewire are not image-based systems, they do not have easy access
to the specific volume of the patient artery under
investigation.
[0063] A method according to an embodiment of the invention rather
involves combining the volume of the targeted artery to the
calculation of the flow and hence, to the calculation of
hemodynamic parameters. The volume of the artery can be obtained by
resolving relation 2, below. L.sub.1 is the initial position where
the contrast agent tracking starts, typically at the ostium of the
artery, and L.sub.2 is the position where the pressure sensitive
portion of the pressure guidewire is located. D(x) is the diameter
of the artery measured by detecting the contour of the artery using
well known edge detection methods. The diameter is integrated along
the length of the artery, i.e., along the centerline of the
artery.
[0064] Volume flow Q.sub.mn is calculated by dividing the volume of
the artery V, by the time for the contrast agent to travel from
L.sub.1 to L.sub.2. Hemodynamic parameters such as microvascular
resistance R.sub.M is calculated by dividing the invasive distal
pressure measurement Pd by volume flow Q.sub.mn. Coronary flow
reserve (CFR) can also be calculated by dividing the blood flow
measured in hyperemia by the blood flow measured at rest (i.e., not
in hyperemia).
V = ( L 2 - L 1 ) 4 .intg. L .times. 1 L .times. 2 .pi. .function.
( D .function. ( x ) ) 2 .times. dx 2 ##EQU00003## Q m .times. n =
V / T m .times. n 3 ##EQU00003.2## R M = P d Q mn 4
##EQU00003.3##
[0065] Relation 2 assumes the artery is circular, while it is never
the case for diseased arteries where the lumen can be substantially
non-circular. Depending on the view, non-circularity can lead to
either the over-estimation or under-estimation of the section of
the artery. The impact on the calculated total artery volume is
quite minimized by the fact that over and under estimation
counter-balances over the length of the artery. As opposed to any
of the geometry based CFD derived pressure-flow characteristics
which are very sensitive to local specific geometry, this method is
based on the overall geometry and is therefore much less sensitive
to local geometry inaccuracies.
[0066] Notwithstanding the relative insensitivity of this method to
local non-circular artery geometry, it is possible to improve lumen
area accuracy by using the density of the contrast agent, i.e.,
using densitometry methods. It is known by those skilled in the art
that the absorption of radiation by a contrast agent depends on the
depth of absorbing medium the radiation travels through
(Beer-Lambert's law). It is therefore possible to estimate the
perpendicular component of the artery by measuring the absorption
that occurs in the section area.
[0067] The level of radiation transmitted through an absorbing
medium is expressed according to relation 5, where I.sub.i is the
incident radiation intensity, I.sub.T is the transmitted radiation
intensity, th is the thickness of absorbing medium, i.e., the depth
of artery perpendicular to the plane of view, and .alpha. is a
constant that corresponds to the contrast agent absorbing
coefficient. It is possible to estimate .alpha. by measuring the
I.sub.T-cal in a section of the same artery, or of another artery,
where it is known to be circular, for example where it is assumed
without disease. Similarly, one can also use the guiding catheter
for the purpose of getting .alpha.. I.sub.i-cal is obtained by
taking a value nearby the position of I.sub.T-cal, but outside the
artery section, while th.sub.cal is the diameter of the artery in
the plane of image. .alpha. is calculated using relation 6. Knowing
.alpha., it is possible to estimate the diameter of the artery
using relation 7, where I.sub.T is the intensity of the section of
artery for which the perpendicular diameter is sought, I.sub.i is
the intensity nearby this section, but outside the artery. Instead
of taking the intensity I.sub.i nearby the artery, it is also
possible to take any point in the background outside of the artery
by first applying the digital subtraction angiography (DSA) method,
which consists in removing background features by subtracting
images absent of contrast agent from images with contrast agent.
Considering relations 5 to 7, logarithm of pixel intensities must
be subtracted.
I T = I i e - .varies. th 5 .varies. = - ln .function. [ I T
.times. .times. ca .times. .times. l / I i .times. .times. ca
.times. .times. l ] t .times. h c .times. a .times. l 6 th = - ln
.function. [ I T / I i ] .varies. = ln .function. [ I i / I T ]
.varies. = ln .function. ( I i ) - ln .function. ( I T ) .alpha. 7
##EQU00004##
Diastolic Flow Measurement
[0068] Second order polynomial can be used to model the
pressure-flow relation of a given artery, the first order term
relating to the viscous friction loss and the second term relating
to the flow separation. In the prior art, the polynomial terms are
found by analyzing the geometry of the artery, segmenting the
artery to apply geometry-based analytical models adapted to each
one of the artery segments. It is therefore quite sensitive to the
exact artery geometry, especially when modelling a stenosis, where
a complex stenosis is modeled as an idealized stenosis, notably
with smooth variation and symmetrical progression of the section
area. However, such geometries are never observed in a real
context, which makes these prior art methods prone to produce an
error in the result.
[0069] Therefore, another embodiment of the invention is based on
the calculation of a second order polynomial characterizing the
artery that is not related to the artery geometry, but which,
instead, is related to its functional characteristics.
[0070] An embodiment of the method is illustrated in FIG. 3 and
described hereinbelow, assuming a synchronicity between the images
and pressure measurements, either by simultaneously acquiring both
modalities in real time or by time stamping both acquisitions.
Considering the time T.sub.mn it takes for the contrast agent to
reach the distal end of the artery is typically shorter than one
heartbeat cycle, this method leads to accurate flow measurement if
the flow within a heartbeat cycle is constant. The flow during the
diastolic phase is however much higher than during the systolic
phase, except for a few exceptions where the systolic flow is
higher than diastolic flow in the right coronary artery (RCA) of
certain patients. In step 10, since the flow mostly propagates
during the diastole, where the flow is, to some extent, constant,
the flow is measured as indicated in previous embodiment, but
limiting volume flow measurement to the diastolic period, or to a
portion of the diastolic period. It is understood here that
although it is preferable measuring flow during the diastole as it
is higher, the same can also be performed during the systole, or
during a portion of the systole. With the patient at rest, the
diastolic volume flow Q.sup.R is measured along with the pressure
drop .DELTA.p.sub.i.sup.R=(P.sub.ai-P.sub.di).sup.R, where i is an
index corresponding to a sequence of pressure measurements at a
given rate, typically around 125 Hz. While inducing hyperemia to
the patient (stressed patient) using a hyperemic agent (such as
adenosine) or more generally a microvascular dilator agent, volume
flow Q.sup.S and pressure drop .DELTA.p.sub.i.sup.s are measured
again during diastolic period while the patient is in hyperemia.
The use of a microvascular dilator agent allows, first, taking
measurements in a first blood flow condition, and then taking
measurements in a second blood flow condition, typically involving
microvascular dilation induced by a proper agent, thus resulting in
a higher blood flow in the second blood flow than in the first
blood flow condition (which has normal flow, or lower flow when
compared to the second blood flow condition).
[0071] Using above measured values in step 11, it is possible to
calculate parameters A and B (FIG. 3, step 10) characterizing the
artery by resolving relations 8 and 9 for A and B.
.DELTA.p.sup.R=AQ.sup.R+B(Q.sup.R).sup.2 (at rest) 8
.DELTA.p.sup.S=AQ.sup.S+B(Q.sup.S).sup.2 (stressed) 9
where,
.DELTA.p.sup.X=.SIGMA..sub.n1.sup.n2.DELTA.p.sub.i.sup.x/(n2-n1)
(10)
and where X above designates either R (Rest) or S (stressed), and
n.sub.2 and n.sub.1 are boundaries of the period (diastole or
portion of diastole) over which the flow was measured.
[0072] Knowing the artery parameters A and B, it is now possible in
step 12 to calculate instant flow associated with any pressure drop
(Pa-Pd). The next step is to calculate, using relation 11, flow
Q.sub.i.sup.x for each pressure drop measurements
.DELTA.p.sub.i=Pa.sub.i-Pd.sub.i over the whole heartbeat cycle
with the patient either at rest or in hyperemia. Volume flow can
finally be calculated over a period of interest n2, n1 using
relation 12, n2 and n1 being selected to obtain values over the
whole heartbeat, during diastole or systole only, or other time
frames.
Q i X = ( - A + A 2 - 4 B .times. .DELTA. .times. .times. p i 2 2 )
2 .times. B 11 Q X = n .times. 1 n .times. 2 .times. Q i X / ( n
.times. 2 - n .times. 1 ) 12 ##EQU00005##
[0073] Microvascular resistance R.sub.M is then calculated in step
13 over the portion of the heartbeat of interest such as whole
heartbeat, systole or diastole, either at rest or in hyperemia,
using relation 13, where P.sub.d.sup.x is the mean distal pressure
over the same period of interest as the period used to calculate
Q.sup.X (relation 14). It is also possible to calculate any
combination of microvascular resistance, such as the ratio between
hyperemic and a resting resistance. It is also possible to
calculate other indices such as CFR using relation 15 among
others.
R M X = P d X Q X 13 P d X = n .times. 1 n .times. 2 .times. P d i
X / ( n .times. 2 - n .times. 1 ) 14 CFR = .SIGMA. n .times.
.times. 1 n .times. .times. 2 .times. Q i S .SIGMA. n .times.
.times. 1 n .times. .times. 2 .times. Q i R , 15 ##EQU00006##
where n.sub.2 and n.sub.1 selected to cover the whole heartbeat
cycle. Other boundary limits can also be selected to calculate a
ratio of hyperemic to resting flow (i.e., a ratio between
measurements made in a first blood flow condition and in a second
blood flow condition, involving a higher flow than in the first
condition as a consequence of the microvascular dilator agent).
Contrast Induced Hyperemia Flow Measurement
[0074] Continuous hyperemia can be induced by various methods, most
commonly using constant intravenous infusion of adenosine.
Intravenous adenosine or other continuous infusion of hyperemic
drug is however not available in every catheterization laboratory,
or "cath lab". It is also possible to induce transient hyperemia
with intra-coronary (IC) bolus of adenosine or other drugs. Because
the duration of IC induced hyperemia is quite short, the operator
would have to synchronize the injection of the hyperemic drug with
the injection of the contrast agent, a method that may be
challenging. Another embodiment consists in injecting a contrast
agent once to measure the flow at resting condition (or first blood
flow condition) as described in embodiments above, followed shortly
after by a second injection of contrast, somewhat synchronized with
hyperemia (or second blood flow condition) induced by contrast
agent, which acts as a microvascular dilator agent that increases
the blood flow to change the blood flow condition from normal to
high. Contrast agent is indeed known to induce hyperemia up to
nearly 80% of full hyperemia. The second flow measurement does not
need to be taken while in full hyperemia, as long as the second
order term of artery parameter B develops, and the pressure
measurement is synchronized with contrast agent-based flow
measurement, artery parameters A and B will be measured with
adequate accuracy. Flow can then be calculated for resting
condition and hyperemic condition by using measured .DELTA.p.sup.S
and .DELTA.p.sup.R respectively.
[0075] As further described below, flow and pressure differences
can be measured over the whole heartbeat cycle or over the diastole
or systole only. Microvascular resistance and other hemodynamic
parameters are calculated as described in previous embodiment using
flow and pressure, either using the entire heartbeat or portion of
it such as the diastole or systole.
Systolic/Diastolic Flow Measurement
[0076] Another preferred embodiment illustrated in FIG. 4 has the
advantage of not requiring any hyperemic agent. In step 20, volume
flow and mean pressure difference (Pa-Pd) are measured as described
with respect to previous embodiments by tracking the contrast agent
wave front during certain periods of the heartbeat cycle, along
with determining the volume of the artery under investigation.
Considering the blood flow is quite different during systole and
diastole, the volume flow will be measured separately during
systole Q.sub.sys and diastole Q.sub.dias. Both these periods
(systolic vs. diastolic) act as first and second blood flow
conditions, in a way which is analogous to resting vs. hyperemic
conditions. More than one injection of contrast may be required to
cover both the systolic and diastolic periods. An audio signal may
also be used to help the operator inject the contrast agent at the
proper time.
[0077] From resting volume flows Q.sub.sys and Q.sub.dias, and
resting mean pressure differences .DELTA.p.sub.sys and
.DELTA.p.sub.dias, artery parameters A and B are calculated in step
21 as described in previous embodiment.
[0078] Measurement of a pressure difference during a single
heartbeat does not require continuous hyperemia and therefore
pressure difference .DELTA.p.sub.i.sup.S is easily measured
following the injection of an intracoronary bolus of adenosine or
the like. As illustrated in step 22, .DELTA.p.sub.i.sup.S is then
used to calculate instant flow Q.sub.i.sup.S using relation 11,
where A and B were found in step 21.
[0079] Volume flow Q.sub.v.sup.S (or Q.sub.v.sup.R) and distal
pressure Pd.sup.S (or Pd.sup.R) are calculated for the period of
interest using relations 12 and 14.
[0080] Microvascular resistance and other hemodynamic parameters
are calculated in step 24 as described in previous embodiments.
Geometry-based Model Flow Measurement Enhancement
[0081] Although the use of contrast agent front wave tracking
methods described above to measure flow in an artery delivers
adequate accuracy for the purposes herein, there may be cases where
there is a need to further improve the result. 1-D CFD model cannot
be used in artery comprising a stenosis as the abrupt changes of
cross sectional areas cause the flow to develop velocity components
perpendicular to the propagation axis along the artery, components
that are not taken into consideration by a 1-D CFD model. 0-D
pressure drop models can also be used, but pressure-drop stenosis
models as mentioned previously assume ideal stenosis geometries
that never exist in clinical set-ups.
[0082] Another embodiment of the invention illustrated in FIG. 5,
starts with the measurement of pressure and flow using contrast
agent as described above and represented by step 30 in this
embodiment, followed by the calculation of the artery parameters as
before. In step 31, the presence of a significant stenosis is
identified either by way of artery parameter B being above a
pre-determined threshold, or by way of visually identifying on the
angiogram the presence of a local stenosis with a percentage
luminal obstruction above 50%, above 60%, above 70% or above
another pre-determined threshold percentage of obstruction.
[0083] In step 32, additional pressures are measured along the
artery segment by slowly pulling back the pressure guidewire while
co-registering pressure along with associated images associated to
each of the pressure measurements along the segment, as described
above. Alternatively, multiple (two or more) pressure measurements
can be recorded at known positions within the artery; minimally the
pressure is measured at a location distal to the stenosis if the
stenosis is proximal in the artery under investigation, or proximal
to the stenosis if the stenosis is distal, or pressures otherwise
adjacent the stenosis and preferably in the longest segment of
artery not containing stenosis. Let us assume herein below that the
stenosis is located in the proximal portion of the artery.
[0084] The flow in the segment of artery for which other pressure
is measured in step 32 can be calculated using well known 1-D CFD
models because it does not contain stenosis. 1-D CFD model can be
derived from Navier-Stokes equations which lead to resolving
relations 16 and 17.
.differential. A .differential. t + .differential. Q .differential.
z = 0 16 .differential. Q .differential. t + .differential.
.differential. z .times. ( .varies. Q 2 A ) + A .rho. .times.
.differential. p .differential. z + K R .times. Q A = 0 , 17
##EQU00007##
where .rho. is the density of blood, .alpha. is the Coriolis
coefficient and K.sub.R is a resistance related to blood viscosity
and velocity profile. If we assume the artery is not elastic and
considering there are no bifurcation, both terms of relation 16
equals to 0 a stated above.
[0085] An alternative to the use of CFD models to calculate the
flow in the artery segment is to use other geometry-based models
such as Poiseuille pressure-drop models, a lumped model, or other
equivalently appropriate models. Poiseuille's law is expressed in
relation 18. Flow Q can thereafter be calculated using the first
part of relation 19 in situation where the pressure guidewire is
slowly pulled back while taking pressure measurements and the
pressure is thereby mapped along the axis of the artery; otherwise
the last part of relation of 19 is used.
.DELTA. .times. p = 8 .times. v .times. l .pi. .times. .times. d 4
.times. Q 18 Q geom = i .times. .DELTA. .times. .times. p i / 8
.times. v .pi. i .times. l i d i 4 = .DELTA. .times. .times. p / 8
.times. v .pi. i .times. l i d i 4 , 19 ##EQU00008##
where .mu. is the viscosity of blood, I is the artery length and d
is the diameter of the artery. It is understood that Q.sub.geom can
be any of the whole heartbeat mean flow, mean systolic or diastolic
flow, either calculated for the resting condition or the hyperemic
condition. It will depend on the portion of .DELTA.p.sub.i that is
used, and on whether pressure was acquired at rest or at
hyperemia.
[0086] Let us assume Q.sub.geom.sup.R is the mean flow at rest.
Although the measurement of volume flow using contrast agent method
may contain some bias errors in determining the absolute volume
flow, the ratio of two flows as obtained in step 30 certainly
delivers a more accurate result as the impact of bias errors is
reduced. It is therefore possible to re-calculate in step 33 the
hyperemic flow Q.sub.geom.sup.S by assuming the ratio of previously
measured flow is accurate and therefore, corrected flow is obtained
with relation 20.
Q g .times. e .times. o .times. m S = Q g .times. e .times. o
.times. m R Q S Q R 20 ##EQU00009##
[0087] Geometry-based flow Q.sub.geom.sup.R and Q.sub.geom.sup.S
and the associated pressure drop are used to re-calculate (step 34)
new artery parameters A and B according to one of the steps 11 or
21. Artery-specific hemodynamic parameters can be calculated as
previously described.
Segmentation of Artery
[0088] A significant branch 7 as shown in FIG. 6 may lead to the
over estimation of the flow since the volume proximal to the branch
carries blood flow that is diverted to the branch and hence, the
volume of the artery in relation 3 should be reduced
proportionately. One method of determining the ratio of flow
splitting is to use well known the allometric scale law such as
described in U.S. patent application publication 2016/0350920
entitled "Methods for the determination of transit time circulatory
systems and applications of the same", incorporated herein by
reference. It is otherwise possible to determine the splitting
ratio by measuring the flow in the branch and the artery using
contrast agent front wave tracking methods. The volume proximal to
the branch used in calculating the flow in relation 3 is corrected
by multiplying the proximal volume by the ratio
Q.sub.arteryQ.sub.branch.
[0089] The method above would lead to reasonably accurate results
if there is no significant pressure drop in the portion of the
artery proximal to the branch. In case there is a significant
stenosis, one method consists in measuring the pressure in the
bifurcation 6, i.e., distal to the stenosis, and measure the
flow-pressure relation in the segment of the artery distal to the
stenosis. Another method consists in taking the two segments
separately and calculate two sets of artery parameters A and B and
calculating respective flows, hence microvascular resistance and
other hemodynamic parameters.
[0090] By pulling back the pressure guidewire 2 in the artery while
taking pressure measurements along the path of the pulling-back
movement, it is possible to separate the artery into a series of
segments, and calculate the artery characteristics A and B, hence
calculate the hemodynamic parameters of interest.
Microvascular Resistance with Collateral
[0091] Collaterals are epicardial vessels connecting arteries
together. As illustrated in FIG. 2, collaterals connection is most
typically distal to the reach of pressure guidewire 2 when it
extends fully distally. At rest, collaterals typically remain
closed. In hyperemia (e.g., when a hyperemic agent is given to the
patient), the presence of a stenosis makes the pressure at the
distal end drop significantly, creating a pressure differential
with the pressure of the supplying artery, hence opening the
collateral. Collateral increases the flow through the
microcirculation, while it contributes also increasing distal
pressure Pd. This contribution to flow and pressure is not linear
and therefore, it does not counter-balance.
[0092] A method to minimize the error caused by the unknown supply
of blood flow from a collateral consists in isolating the
contribution of the collateral by measuring the wedge pressure and
include it in the calculation of the microvascular resistance
(Martinez et al, Cor. Art. Dis., 2015). Because wedge pressure is
not part of everyday clinical workflow, another method was
developed that uses a relation between the FFR.sub.myo and
FFR.sub.cor derived from general population. There is a need to
better take into account the contribution of collaterals in the
measurement of the microvascular resistance.
[0093] The systolic and diastolic hyperemic microvascular
resistances in presence of a collateral can be expressed with
relations 21.
R M - s .times. y .times. s S = P d - sy .times. s S ( Q A - s
.times. y .times. s S + Q C - sy .times. s S ) .times. .times. and
.times. .times. R M - dias S = P d - dias S ( Q A - dias S + Q C -
dias S ) 21 ##EQU00010##
where Q.sub.A is the flow from the artery under investigation and
Qc is the collateral flow.
[0094] As discussed, a collateral opens in response to hyperemia
and therefore, resting microvascular resistances can be expressed
with relations 22.
R M - s .times. y .times. s R = P d - sys R Q A - sys R .times.
.times. and .times. .times. R M - dias R = P d - dias R Q A - dias
R 22 ##EQU00011##
[0095] If we assume the pressure driving the blood flow through the
collateral is Pa, collateral flow can be expressed as follow:
Q C - sys / dias S = .DELTA. .times. p d - sys / dias S R C 23
##EQU00012##
where Rc is the resistance of the collateral and
.DELTA..sub.p.sup.S.sub.d-sys/dias is either the systolic or
diastolic hyperemic pressure difference Pa-Pd. Collateral
resistance is not flow-dependent and therefore,
R.sub.c-sys=R.sub.c-dias=R.sub.C.
[0096] The ratio K of the diastolic to systolic resistance at rest
can be calculated from relations 22 as follow.
K = R M - sys R R M - dias R = Q dias R Q s .times. y .times. s R P
d - sys R P d - dias R 24 ##EQU00013##
[0097] Assuming the ratio of systolic to diastolic resistance in
hyperemia is the same as the ratio at rest, relations 21, 23 and 24
leads to:
R C = ( K P dias S .DELTA. .times. .times. P d - sys S + P sys S
.DELTA. .times. .times. P d - dias S ) ( P sys S .DELTA. .times.
.times. P d - dias S + P dias S .DELTA. .times. .times. P d - sys S
) 25 ##EQU00014##
[0098] Collateral flow Q.sub.C.sup.S can be calculated using Rc of
relation 25 into relation 23. Hemodynamic parameters can then be
calculated by considering the flow within the microvascular
resistance is the addition of Q.sub.C.sup.S and Q.sub.A.sup.S
Post-PCI Hemodynamic Assessment
[0099] In resting condition, the relation between pressure and flow
is typically linear. In presence of two or more stenoses, it is
possible to easily determine the impact of stenting one stenosis
(after performing a percutaneous coronary intervention or PCI) by
removing the pressure drop caused by the stenosis to be removed,
and calculate the distal pressure and the post-PCI value of any of
the existing resting indices such as Pd/Pa, iFR (instantaneous
Wave-free index) or dPR (diastolic pressure ratio). This is however
not possible for FFR as it is a hyperemic index. A method to
determine the impact on FFR after removing one stenosis requires
wedge pressure measurement. As mentioned previously, this is not
common practice in clinical set-ups.
[0100] A preferred way would involve characterizing the artery
according to one of the previous methods, preferably a method that
includes segmenting the artery. Although segmentation may include
the two stenoses and along with other portions of the artery, for
the sake of simplifying the description, we will herein assume the
segments include a first segment 40 from the ostium to the middle
of the stenoses and a second segment 41 from the middle of the
artery to the distal end (FIG. 7). This obviously assumes there is
no significant diffuse disease. As already mentioned, if the
lesions are diffuse along the artery, they can be modeled by
additional segmentations. Let us assume flow is measured according
to step 10 or 20, and pressure is measured according to step 11 at
both the distal end Pd and in between the stenosis Ps by pulling
the pressure guidewire back in position. Let us assume no
significant branch is present, there are now two sets of relations
8 and 9 for each segment 40 and 41. Flow in both segments is the
same while pressure difference of first segment is
.DELTA.p.sub.s1=p.sub.a-p.sub.s and
.DELTA.P.sub.s2=(p.sub.a-p.sub.d)-.DELTA.Ap.sub.s1. Parameters
A.sub.s1 and B.sub.s1 for first segment 40 and A.sub.s2 and
B.sub.s2 for the second segment 41 are known. From there, we
calculate mean microvascular resistance R.sub.M.
[0101] Assuming no diffuse disease is present in the first segment
40, we can assume the stenting of one stenosis, let us assume
stenosis 1, leads to the elimination of the pressure drop in this
segment. The artery can therefore be modeled using the second set
of parameters only. Removing stenosis 1 however leads to a new
flow, given by Q.sub.Post-PCl=P.sub.d post-PCl/R.sub.M. By
inserting this relation into relation 9 leads to
p a S - p d s = A S .times. 2 ( p d s R M ) + B S .times. 2 ( p d s
R M ) 2 , 26 ##EQU00015##
which is easily resolved for p.sub.d.sup.s by posing p.sub.a.sup.s.
Post-PCI FFR is then FFR=p.sub.d.sup.s/p.sub.a.sup.s. It is
understood this is one example and other segmentations can be used
to also take into consideration diffuse diseases or other features
as provided herein.
Other Models
[0102] Although the description herein is mostly based on the use
of a second-order model, i.e., a model relating the pressure drop
with the addition of a linear term and a second-order blood flow
term such as relations 8 and 9, to characterize the artery
pressure-flow relation, other models can be used. For instance,
models where two or more pressure measurements and corresponding
(and simultaneous) images are acquired while the flow is different
such as during systole vs. diastole, or during resting vs.
hyperemic conditions, can be used as well. The systole vs. diastole
act as first and second blood flow conditions, and so do the
resting vs. hyperemic conditions. By way of non-limiting examples,
other models may include a third order term, or may comprise
differential or integral terms, time-dependent terms,
space-dependent terms, etc.
Co-registration
[0103] Considering the embodiments above includes hemodynamic
information that relates to specific regions of the artery, it
would facilitate the visualization and assessment of the
hemodynamic functions if they were integrated along with the
angiogram in way similar to U.S. patent application US 2006/0052700
entitled "Pressure measurement system", incorporated herein by
reference in its entirety.
[0104] Although the microvascular resistance is considered herein
as purely resistive, it is also possible to assume the
microvascular impedance contains a capacitance in addition to
resistors (Morris et al., JACC Vol. 8, No. 9 2015), and calculate
both the microvascular resistance and capacitance.
[0105] According to the embodiments of the invention, a computing
system is required to advantageously compute the hemodynamic
parameters listed above according to the relations also described
above in a timely manner, since the values need to be computed in
real time during intervention for rapid and critical
decision-making. The computing system comprises a memory for
storing instructions, notably those for computing the hemodynamic
parameters. A processor in communication with the memory executes
the instructions to perform the computations.
[0106] The computing system has ports of communication (which can
be wired or wireless) for receiving pressure measurements from the
pressure guidewire 2. The pressure guidewire 2 comprises a pressure
sensor which transmits its signals through a communication means
(electrical or preferably optical) through the pressure guidewire,
to a receiver which processes the signal to feed it to the
computing system, or directly to the computing system if it is
adapted to receive such a signal from the pressure guidewire. The
computing system thus receives pressure measurements as required by
the embodiments described herein.
[0107] Image data taken by imaging instruments is also fed to the
computing system simultaneously to the data from the pressure
guidewire, such that pressure measurements are simultaneously
complemented with real image data of local and personalized artery
geometry.
[0108] Instead of using a non-invasive method as a replacement for
the invasive methods, both invasive (pressure guidewire) and
non-invasive (imaging) are used together as complements in order to
calculate more accurate hemodynamic parameters. The computing
system receives both data sources to compute in real-time the
hemodynamic parameters and offer to the clinician a hemodynamic
parameter value that is more representative of the real local
conditions in the coronary artery being investigated, thus allowing
better decision making in the cath lab as the hemodynamic
parameters better reflect reality instead of assuming incorrect
generalities regarding artery geometry.
[0109] While preferred embodiments have been described above and
illustrated in the accompanying drawings, it will be evident to
those skilled in the art that modifications may be made without
departing from this disclosure. Such modifications are considered
as possible variants comprised in the scope of the disclosure.
* * * * *