U.S. patent application number 17/159114 was filed with the patent office on 2021-07-22 for devices for determining flow reserve within a luminal organ.
This patent application is currently assigned to 3DT Holdings, LLC. The applicant listed for this patent is 3DT Holdings, LLC. Invention is credited to Ghassan S. Kassab.
Application Number | 20210219854 17/159114 |
Document ID | / |
Family ID | 1000005495403 |
Filed Date | 2021-07-22 |
United States Patent
Application |
20210219854 |
Kind Code |
A1 |
Kassab; Ghassan S. |
July 22, 2021 |
DEVICES FOR DETERMINING FLOW RESERVE WITHIN A LUMINAL ORGAN
Abstract
Devices, systems, and methods to determine fractional flow
reserve. At least one method for determining fractional flow
reserve of the present disclosure comprises the steps positioning a
device comprising at least two sensors within a luminal organ at or
near a stenosis, wherein the at least two sensors are separated a
predetermined distance from one another, operating the device to
determine flow velocity of a second fluid introduced into me
luminal organ to temporarily displace a first fluid present within
the luminal organ, and determining fractional flow reserve at or
near the stenosis based upon the flow velocity, a mean aortic
pressure within the luminal organ, and at least one cross-sectional
area at or near the stenosis. Devices and systems useful for
performing such exemplary methods are also disclosed herein.
Inventors: |
Kassab; Ghassan S.; (La
Jolla, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
3DT Holdings, LLC |
Dan Diego |
CA |
US |
|
|
Assignee: |
3DT Holdings, LLC
San Diego
CA
|
Family ID: |
1000005495403 |
Appl. No.: |
17/159114 |
Filed: |
January 26, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15451820 |
Mar 7, 2017 |
10898086 |
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17159114 |
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13070183 |
Mar 23, 2011 |
9585572 |
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15451820 |
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13120308 |
Mar 22, 2011 |
8702613 |
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PCT/US2009/057800 |
Sep 22, 2009 |
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13070183 |
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61098837 |
Sep 22, 2008 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/028 20130101;
A61B 5/053 20130101; A61B 5/02007 20130101; A61B 5/0275 20130101;
A61B 5/6852 20130101; A61B 5/026 20130101; A61B 5/02158 20130101;
A61B 5/0295 20130101 |
International
Class: |
A61B 5/0215 20060101
A61B005/0215; A61B 5/0275 20060101 A61B005/0275; A61B 5/02 20060101
A61B005/02; A61B 5/0295 20060101 A61B005/0295; A61B 5/026 20060101
A61B005/026; A61B 5/00 20060101 A61B005/00 |
Claims
1. A device for determining a flow reserve of a fluid within a
luminal organ, the device comprising: an elongated body sized and
shaped to fit within a luminal organ; and at least two sensors
separated a predetermined distance from one another; wherein the
device operable to determine a flow velocity of a fluid within a
mammalian luminal organ and to obtain conductance data within the
mammalian luminal organ useful to determine a cross-sectional area
of the mammalian luminal organ, when at least part of the device is
positioned within the mammalian luminal organ; and wherein the
device is configured to operably couple to a data acquisition and
processing system configured to (a) determine the cross-sectional
area using the conductance data, (b) determine a pressure
measurement within the mammalian luminal organ using the flow
velocity and the cross-sectional area, without the use of a
pressure sensor, and (c) determine a flow reserve at or near a
stenosis within the mammalian luminal organ using the
cross-sectional area, the flow velocity, and the pressure
measurement.
2. The device of claim 1, wherein the device is operable to
determine the flow reserve based upon the flow velocity, the
pressure measurement, and the cross-sectional area comprising a
cross-sectional area of the luminal organ distal to the stenosis
and a cross-sectional area of the luminal organ proximal to the
stenosis.
3. The device of claim 1, wherein the device is operable to
determine the flow reserve based upon the flow velocity, the
pressure measurement, and the cross-sectional area comprising a
cross-sectional area of the luminal organ distal to the stenosis, a
cross-sectional area of the luminal organ proximal to the stenosis,
and a cross-sectional area of the luminal organ at the
stenosis.
4. The device of claim 1, forming part of an impedance system, the
impedance system further comprising the data acquisition and
processing system.
5. A device for determining a flow reserve of a fluid within a
luminal organ, the device comprising: an elongated body sized and
shaped to fit within a luminal organ; and at least two sensors
positioned along the elongated body a predetermined distance from
one another; wherein the device is operable to detect a first fluid
with a first parameter having a first value using at least one of
the at least two sensors when the device is positioned within the
luminal organ; wherein the device is further operable to detect a
second fluid having a second parameter, wherein the second
parameter of the second fluid has a second value different from the
first value, upon introduction of the second fluid within the
luminal organ at or near the at least two sensors; and wherein the
device is further operable to determine a flow reserve of a fluid
within the luminal organ when the device is positioned within the
luminal organ at or near a stenosis, wherein the flow reserve is
based upon a flow velocity obtained by the device, a mean aortic
pressure within the luminal organ, and at least one cross-sectional
area at or near the stenosis.
6. The device of claim 5, wherein the second fluid detected by the
at least two sensors allows for the determination of the flow
velocity based upon timing of the detected second fluid by the at
least two sensors and the distance between the at least two
sensors.
7. The device of claim 5, wherein the device is operable to
determine the flow reserve based upon the flow velocity obtained by
the device, the mean aortic pressure within the luminal organ, a
cross-sectional area of the luminal organ distal to the stenosis,
and a cross-sectional area of the luminal organ proximal to the
stenosis.
8. The device of claim 5, wherein the device is operable to
determine the flow reserve based upon the flow velocity obtained by
the device, the mean aortic pressure within the luminal organ, a
cross-sectional area of the luminal organ distal to the stenosis, a
cross-sectional area of the luminal organ proximal to the stenosis,
and at least one cross-sectional area of the luminal organ at the
stenosis.
9. The device of claim 5, wherein the flow velocity allows for the
determination of volumetric flow based upon the flow velocity and
the at least one cross-sectional area.
10. The device of claim 5, wherein the flow reserve is further
based upon a blood viscosity.
11. The device of claim 5, wherein the determination of the flow
reserve is made using a data acquisition and processing system
operably coupled to the device.
12. The device of claim 5, forming part of an impedance system, the
impedance system further comprising the data acquisition and
processing system.
13. A device for determining a flow reserve of a fluid within a
luminal organ, the device comprising: an elongated body sized and
shaped to fit within a luminal organ; at least one pair of
excitation electrodes positioned along the elongated body; and at
least two pairs of detection electrodes positioned along the
elongated body between the at least one pair of excitation
electrodes, the at least two pairs of detection electrodes
positioned a predetermined distance from each other; wherein when
the device is positioned within the luminal organ, the device is
operable to detect a first conductance of a first fluid having a
first conductivity within the luminal organ using the at least two
pairs of detection electrodes, the device further operable to
detect a second conductance of a second fluid having a second
conductivity using the at least two pairs of detection electrodes
upon introduction of the second fluid within the luminal organ at
or near the at least two pairs of detection electrodes; and wherein
the device is further operable to determine a flow reserve of a
fluid within the luminal organ when the device is positioned within
the luminal organ at or near a stenosis, wherein the flow reserve
is based upon the a flow velocity obtained by the device, a mean
aortic pressure within the luminal organ, and at least one
cross-sectional area at or near the stenosis.
14. The device of claim 13, wherein the second fluid detected by
using the at least two pairs of detection electrodes allows for the
determination of flow velocity based upon timing of the detected
second fluid by using the at least two pairs of detection
electrodes and the distance between the at least two pairs of
detection electrodes.
15. The device of claim 13, wherein the device is operable to
determine the flow reserve based upon the flow velocity obtained by
the device, the mean aortic pressure within the luminal organ, a
cross-sectional area of the luminal organ distal to the stenosis,
and a cross-sectional area of the luminal organ proximal to the
stenosis.
16. The device of claim 13, wherein the device is operable to
determine the flow reserve based upon the flow velocity obtained by
the device, the mean aortic pressure within the luminal organ, a
cross-sectional area of the luminal organ distal to the stenosis, a
cross-sectional area of the luminal organ proximal to the stenosis,
and at least one cross-sectional area of the luminal organ at the
stenosis.
17. The device of claim 13, wherein the flow velocity allows for
the determination of volumetric flow based upon the flow velocity
and the at least one cross-sectional area.
18. The device of claim 13, wherein the determination of the flow
reserve is made using a data acquisition and processing system
operably coupled to the device.
19. The device of claim 13, forming part of an impedance system,
the impedance system further comprising the data acquisition and
processing system.
Description
PRIORITY
[0001] The present application is related to, claims the priority
benefit of, and is a U.S. continuation patent application of, U.S.
patent application Ser. No. 15/451,820, filed Mar. 7, 2017 and
issued as U.S. Pat. No. 10,898,086 on Jan. 26, 2021, which is
related to, claims the priority benefit of, and is a U.S.
continuation patent application of, U.S. patent application Ser.
No. 13/070,183, filed Mar. 23, 2011 and issued as U.S. Pat. No.
9,585,572 on Mar. 7, 2017, which is related to, claims the priority
benefit of, and is a U.S. continuation patent application of, U.S.
patent application Ser. No. 13/120,308, filed Mar. 22, 2011 and
issued as U.S. Pat. No. 8,702,613 on Apr. 22, 2014, which is
related to, claims the priority benefit of, and is a U.S. national
stage application of, International Patent App. Ser. No.
PCT/US2009/057800, filed Sep. 22, 2009, which is related to, and
claims the priority benefit of, U.S. Provisional Patent Application
Ser. No. 61/098,837, filed Sep. 22, 2008. The contents of each of
these applications and patent are hereby incorporated by reference
in their entirety into this disclosure.
BACKGROUND
[0002] Coronary heart disease remains the leading cause of
morbidity and mortality in the United States and the developed
world. Although the current "gold standard" for assessing coronary
artery disease (CAD) is angiography, it has serious limitations in
evaluating the functional significance of intermediate coronary
lesions (comprising 30-70% stenosis). Coronary angiography relies
on a visual interpretation of coronary anatomy. A number of studies
have documented the large intra- and inter-observer variability
that results from visual grading of coronary stenotic lesions.
Moreover, studies have shown a lack of correlation between the
angiographic delineated stenosis with their physiologic severity on
coronary flow. This stems from the highly non-linear relation
between the degree of stenosis and the change in blood flow.
Typically, the blood flow remains unchanged until the degree of
stenosis reaches a critical range (typically >80%), at which
point the decrease in flow is quite dramatic. Lesions that are not
functionally significant (i.e., do not reduce the flow) may not
need treatment. Hence, there is a need for complementary methods to
conventional coronary arteriograms that combine coronary anatomy
and physiology to assess CAD accurately.
[0003] Blood vessel diameter or cross-sectional area gives anatomic
measures of stenosis severity. Coronary blood flow, on the other
hand, reflects coronary hemodynamic function and can be used to
assess functional severity of stenosis through parameters such as
coronary flow reserve (CFR) and fractional flow reserve (FFR). CFR,
defined as the ratio of hyperemic (induced by pharmacological
agents) to resting flow in a coronary artery. It has been
previously found that a significant stenosis leading to inducible
ischemia occurs when CFR has a value less than 2.0. Normally, the
coronary circulation has a flow reserve of 3-5 times that of normal
resting blood flow. This reserve stems from the tone of small blood
vessels (microvascular bed). In disease, the microvascular bed
dilates and uses some of its reserve to compensate for the pressure
drop to the stenosis. Hence, a low CFR value can characterize
disease in the epicardial arteries or the distal resistive
microvascular bed.
[0004] CFR can be estimated from hyperemic and resting blood
velocities measured by a Doppler guidewire. This method is based on
the principle of Doppler which requires that the piezo-electric
crystal to be at a specific angle to the flowing blood. Since this
condition is very difficult to meet in clinical practice as the tip
of the wire is difficult to align with the direction of flow, the
measurements are not reliably accurate and this method has not
enjoyed clinical utility. Recent developments have introduced
methods and systems for accurate determination of cross-sectional
area of blood vessels including coronary arteries. Simultaneous
measurements of cross-sectional area and flow (including CFR) would
provide a clinician with a greater insight in the contribution of
the epicardial vessel and microvasculature to total resistance to
myocardial blood flow.
[0005] In summary, there are well-known limitations to the use of
visual estimation to assess the severity of coronary artery disease
and luminal stenosis. This is especially true in the case of
intermediate coronary lesion where coronary angiography is very
limited in distinguishing ischemia-producing intermediate coronary
lesions from non-ischemia-producing ones. For this reason, a
functional measure of stenosis severity is desirable. Previous
devices involving Doppler flow wires also have serious limitations
as referenced above. Hence, there is clearly a need for a simple,
accurate, cost effective solution to determination of coronary
blood flow in routine practice.
BRIEF SUMMARY
[0006] in at least one embodiment of a method for determining
fractional flow reserve within a luminal organ of the present
disclosure, the method comprises the steps of positioning a device
comprising at least two sensors within a luminal organ at or near a
stenosis, wherein the at least two sensors are separated a
predetermined distance from one another, operating the device to
determine flow velocity of a second fluid introduced into the
luminal organ to temporarily displace a first fluid present within
the luminal organ, and determining fractional flow reserve at or
near the stenosis based upon the flow velocity, a mean aortic
pressure within the luminal organ, and at least one cross-sectional
area at or near the stenosis. In at least one embodiment, the at
least one cross-sectional area comprises a cross-sectional area of
the luminal organ distal to the stenosis, a cross-sectional area of
the luminal organ proximal to the stenosis, and at least one
cross-sectional area of the luminal organ at the stenosis.
[0007] In another exemplary embodiment of a method for determining
fractional flow reserve within a luminal organ of the present
disclosure, the step of determining fractional flow reserve is
further based upon a determination of volumetric flow between the
at least two sensors. In an additional embodiment, the
determination of volumetric flow is based upon the flow velocity
and the at least one cross-sectional area.
[0008] In an exemplary embodiment of a method for determining
fractional flow reserve within a luminal organ of the present
disclosure, the step of operating the device to determine flow
velocity of a fluid introduced into the luminal organ comprises the
steps of detecting the first fluid within the luminal organ using
at least one of the at least two sensors, wherein the first fluid
has a first parameter having a first value, introducing the second
fluid into the luminal organ, said second fluid temporarily
displacing the first fluid within the luminal organ at the site of
introduction, wherein the second fluid has a second parameter
having a second value, the second value differing from the first
value, detecting the second value of the second parameter of the
second fluid by the at least two sensors, measuring time of
detection of the second value of the second parameter of the second
fluid by each of the at least two sensors, and determining flow
velocity of the second fluid within the luminal organ based upon
the time of detection of the second value of the second parameter
of the second fluid by each of the at least two sensors. In at
least one embodiment, the first parameter and the second parameter
are conductivity, pH, temperature, or an optically-detectable
substance. In another exemplary embodiment, the method further
comprises the step of diagnosing a disease based upon the
determination of flow velocity within a luminal organ. In yet
another embodiment, the determination of fractional flow reserve is
indicative of a degree of stenosis within the lumina organ. In an
exemplary embodiment, the step of determining fractional flow
reserve is performed using a data acquisition and processing
system. In at least one embodiment, the first fluid comprises blood
and the second fluid comprises saline.
[0009] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ of the present
disclosure, the method is bawd upon at least the detection of an
introduced bolus within a luminal organ, wherein the introduced
bolus has a parameter with a value different from the value of the
parameter of the fluid present within the luminal organ prior to
the introduction of the bolus.
[0010] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the method comprises the steps of
positioning a device comprising a pair of excitation electrodes and
at least two pairs of detection electrodes within a luminal organ
at or near a stenosis, wherein the at least two pairs of detection
electrodes are separated a predetermined distance from each other,
operating the device to determine flow velocity of a second fluid
introduced into the luminal organ, said second fluid temporarily
displacing a first fluid present within the luminal organ, and
determining fractional flow reserve at or near the stenosis based
upon the flow velocity, a mean aortic pressure within the luminal
organ, and at least one cross-sectional area at or near the
stenosis. In at least one embodiment, the at least one
cross-sectional area comprises a cross-sectional area of the
luminal organ distal to the stenosis, a cross-sectional area of the
luminal organ proximal to the stenosis, and at least one
cross-sectional area of the luminal organ at the stenosis.
[0011] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the step of determining fractional flow
reserve is further based upon a determination of volumetric flow
between the at least two pairs of detection electrodes. In another
embodiment, the determination of volumetric flow is based upon the
flow velocity and the at least one cross-sectional area.
[0012] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the step of operating the device to
determine flow velocity of a fluid introduced into the luminal
organ comprises the steps of activating the pair of excitation
electrodes to generate a field detectable by the detection
electrodes, detecting conductance of the first fluid having a first
conductivity within the luminal organ using at least one pair of
the at least two pairs of detection electrodes, introducing the
second fluid having a second conductivity into the luminal organ,
said second fluid temporarily displacing the first fluid within the
luminal organ at the site of introduction, wherein the first
conductivity does not equal the second conductivity, detecting the
conductance of the second fluid by the at least two pairs of
detection electrodes, measuring time of conductance detection of
the second fluid by each of the at least two pairs of detection
electrodes, and determining flow velocity of the second fluid
within the luminal organ based upon the time of conductance
detection by each of the at least two pairs of detection
electrodes.
[0013] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the step of operating the device to
determine flow velocity of a fluid introduced into the luminal
organ comprises the steps of activating the pair of excitation
electrodes to generate a field, detecting conductance of the first
fluid having a first conductivity within the luminal organ using at
least one pair of the at least two pairs of detection electrodes,
introducing the second fluid having a second conductivity into the
luminal organ, said second fluid temporarily displacing the first
fluid within the luminal organ at the site of introduction, wherein
the first conductivity does not equal the second conductivity,
detecting the conductance of the second fluid by the at least two
pairs of detection electrodes, measuring time of conductance
detection of the second fluid using at least one pair of the at
least two pairs of detection electrodes, and determining flow
velocity of the second fluid within the luminal organ based upon
the time of conductance detection using (a) a first excitation
electrode of the pair of excitation electrodes and a first pair of
detection electrodes of the at least two pairs of detection
electrodes, and (b) a second excitation electrode of the pair of
excitation electrodes and a second pair of detection electrodes of
the at least two pairs of detection electrodes.
[0014] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the method further comprises the step of
diagnosing a disease based upon the determination of flow velocity
within a luminal organ. In another embodiment, the determination of
fractional flow reserve is indicative of a degree of stenosis
within the luminal organ. In yet another embodiment, the step of
determining fractional flow reserve is performed using a data
acquisition and processing system. In at least one exemplary
embodiment, the first fluid comprises blood and the second fluid
comprises saline.
[0015] In at least one embodiment of a method for determining
fractional flow reserve within a luminal organ using impedance of
the present disclosure, the method is based upon at least the
detection of an introduced bolus within a luminal organ, wherein
the introduced bolus has a conductivity different from the
conductivity of the fluid present within the luminal organ prior to
the introduction of the bolus.
[0016] In at least one embodiment of a device for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the device comprises an elongated body sized
and shaped to fit within a luminal organ, and at least two sensors
positioned along the elongated body a predetermined distance from
one another, wherein the device is operable to detect a first fluid
with a first parameter having a first value using at least one of
the at least two sensors when the device is positioned within the
luminal organ, and wherein the device is further operable to detect
a second fluid having a second parameter, wherein the second
parameter of the second fluid has a second value different from the
first value, upon introduction of the second fluid within the
luminal organ at or near the at least two sensors. In at least one
embodiment, the second fluid detected by the at least two sensors
allows for the determination of flow velocity based upon timing of
the detected second fluid by the at least two sensors and the
distance between the at least two sensors. In another embodiment,
the device is further operable to determine fractional flow reserve
when the device is positioned within the luminal organ at or near a
stenosis, wherein the fractional flow reserve is based upon the
flow velocity, a mean aortic pressure within the luminal organ, and
at least one cross-sectional area at or near the stenosis. In yet
another embodiment, the at least one cross-sectional area comprises
a cross-sectional area of the luminal organ distal to the stenosis,
a cross-sectional area of the luminal organ proximal to the
stenosis, and at least one cross-sectional area of the luminal
organ at the stenosis.
[0017] In at least one embodiment of a device for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the flow velocity allows for the determination
of volumetric flow based upon the flow velocity and a
cross-sectional area of the luminal organ. In another embodiment,
the determination of fractional flow reserve is made using a data
acquisition and processing system.
[0018] In at least one embodiment of a device for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the device comprises an elongated body sized
and shaped to fit within a luminal organ, at least one pair of
excitation electrodes positioned along the elongated body, and at
least two pairs of detection electrodes positioned along the
elongated body between the at least one pair of excitation
electrodes, wherein the at least two pairs of detection electrodes
are positioned a predetermined distance from each other, wherein
when the device is positioned within the luminal organ, the device
is operable to detect a first conductance of a first fluid having a
first conductivity within the luminal organ using the at least two
pairs of detection electrodes, the device further operable to
detect a second conductance of a second fluid having a second
conductivity using the at least two pairs of detection electrodes
upon introduction of the second fluid within the luminal organ at
or near the at least two pairs of detection electrodes. In at least
one embodiment, the second fluid detected by using the at least two
pairs of detection electrodes allows for the determination of flow
velocity based upon timing of the detected second fluid by using
the at least two pairs of detection electrodes and the distance
between the at least two pairs of detection electrodes.
[0019] In at least one embodiment of a system for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the system comprises a device for determining
fractional flow reserve, the device comprising an elongated body
sized and shaped to fit within a luminal organ, and at least two
sensors positioned along the elongated body a predetermined
distance from one another, wherein the device is operable to detect
a first fluid with a first parameter having a first value using at
least one of the at least two sensors when the device is positioned
within the luminal organ, and wherein the device is further
operable to detect a second fluid having a second parameter,
wherein the second parameter of the second fluid has a second value
different from the first value, upon introduction of the second
fluid within the luminal organ at or near the at least two sensors,
and a data acquisition and processing system in communication with
the device, the data acquisition and processing system operable to
calculate flow velocity of the second fluid based upon timing of
the detected second fluid by the at least two sensors and the
distance between the at least two sensors.
[0020] In at least one embodiment of a system for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the system comprises a device for determining
fractional flow reserve, the device comprising an elongated body
sized and shaped to fit within a luminal organ, at least one pair
of excitation electrodes positioned along the elongated body, and
at least two pairs of detection electrodes positioned along the
elongated body between the at least one pair of excitation
electrodes, wherein the at least two pairs of detection electrodes
are positioned a predetermined distance from each other, wherein
when the device is positioned within the luminal organ, the device
is operable to detect a first conductance of a first fluid having a
first conductivity within the luminal organ using the at least two
pairs of detection electrodes, the device further operable to
detect a second conductance of a second fluid having a second
conductivity using the at least two pairs of detection electrodes
upon introduction of the second fluid within the luminal organ at
or near the at least two pairs of detection electrodes, and a data
acquisition and processing system in communication with the device,
the data acquisition and processing system operable to calculate
flow velocity of the second fluid based upon timing of the detected
second fluid by using the at least two pairs of detection
electrodes and the distance between the at least two pairs of
detection electrodes.
[0021] In at least one embodiment of a system for determining
fractional flow reserve of a fluid within a luminal organ of the
present disclosure, the data acquisition and processing system is
further operable to determine fractional flow reserve when the
device is positioned within the luminal organ at or near a
stenosis, wherein the fractional flow reserve is based upon the
flow velocity, a mean aortic pressure within the luminal organ, and
at least one cross-sectional area at or near the stenosis. In
another embodiment, the flow velocity allows for the determination
of volumetric flow based upon the flow velocity and a
cross-sectional area of the luminal organ.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 shows an exemplary embodiment of a portion of a
device useful for determining flow velocity and volumetric flow
comprising two sensors positioned along a body of the device,
according to the disclosure of the present application;
[0023] FIG. 2 shows an exemplary embodiment of a portion of a
device useful for determining flow velocity and volumetric flow
comprising a hexa-polar (six electrode) arrangement of electrodes
with two outer electrodes (E) and two sets of detection electrodes
(D), according to the disclosure of the present application;
[0024] FIG. 3A shows a graph demonstrating the increase in total
conductance over time during a transient injection of 1.5% sodium
chloride solution into a pig coronary artery in accordance with at
least one method of the disclosure of the present application;
[0025] FIG. 3B shows a graph demonstrating the decrease in total
conductance over time during a transient injection of 0.45% sodium
chloride solution into a pig coronary artery in accordance with at
least one method of the disclosure of the present application;
[0026] FIG. 4 shows changes in conductance over time at electrodes
1 and 2 (as shown in FIG. 2) during a 0.9% sodium chloride
injection in accordance with at least one method of the disclosure
of the present application;
[0027] FIG. 5 shows an exemplary embodiment of a system useful for
determining flow velocity and volumetric flow according to the
disclosure of the present application;
[0028] FIG. 6 shows a block diagram of a method for determining
flow velocity according to the disclosure of the present
application;
[0029] FIG. 7 shows a block diagram of a method for determining
flow velocity using impedance according to the disclosure of the
present application;
[0030] FIG. 8 shows a schematic of displacement of saline by blood
after the injection of saline according to the disclosure of the
present application;
[0031] FIG. 9 shows a graph depicting the voltage drop across
detection electrodes according to the disclosure of the present
application;
[0032] FIG. 10 shows a schematic of isopotential field lines for a
coronary artery according to the disclosure of the present
application;
[0033] FIG. 11 shows a graph showing the validation of a finite
element model according to the disclosure of the present
application;
[0034] FIG. 12 shows a graph showing two sets of simultaneous
voltage-time or conductance-time curves according to the disclosure
of the present application; and
[0035] FIG. 13 shows another graph showing the validation of a
finite element model according to the disclosure of the present
application.
DETAILED DESCRIPTION
[0036] For the purposes of promoting an understanding of the
principles of the present disclosure, reference will now be made to
the embodiments illustrated in the drawings, and specific language
will be used to describe the same. It will nevertheless be
understood that no limitation of the scope of this disclosure is
thereby intended.
[0037] The disclosure of the present application provides devices,
systems, and methods for determining fractional flow reserve (FFR),
including devices, systems, and methods for determining FFR using
impedance. An exemplary method for performing the same would
utilize one or more devices (or elements/features of such a device)
operable to detect a change in at least one characteristic within a
vessel flow based upon the introduction of a change to the initial
flow. Such methods, and devices and systems for performing such
methods, are useful for the diagnosis of disease (including CAD) by
providing accurate values for flow velocity, whereby changes in
flow velocity and/or volumetric flow may be indicative of a low or
high degree of stenosis. Such changes in flow velocity and/or
volumetric flow may be identified by comparing flow velocity and/or
volumetric flow at various vessels and/or organs (generally
referred to as "luminal organs") within a body, and or by comparing
flow velocity and/or volumetric flow taken at various times.
[0038] For purposes of the present application, an "indicator"
shall mean a substance introduced to, for example, a blood vessel,
that includes at least one parameter different than the native
fluid flowing within such a vessel, which may include, but is not
limited to, various chemical changes like osmolarity and pH, for
example, and/or optical, electrical, and/or thermal changes.
Exemplary indicators may then be detectable by a "sensor," which
may comprise any number of applicable sensors useful to detect such
indicators. Exemplary sensors may include, but are not limited to,
detection electrodes, pH sensors, thermocouples, and optical
sensors, which are operable to detect one or more indicators. A
"parameter," as referenced herein, refers to an aspect of an
indicator that may be detected by one or more sensors, including,
but not limited to, conductivity, pH, temperature, and/or
optically-detectable substances. The disclosure of the present
application is not intended to be limited to the specific
indicators and/or sensors disclosed herein, as other indicators
and/or sensors suitable for the devices, systems, and methods for
determining FFR not disclosed herein may also be suitable for one
or more applications of the same.
[0039] An exemplary embodiment of at least a portion of a device
useful for determining FFR using impedance is shown in FIG. 1. As
shown in FIG. 1, device 100 comprises two sensors 102 (each sensor
102 labeled "S" in FIG. 1, whereby one sensor 102 is further
labeled "1" and the second sensor 102 is further labeled "2")
positioned along the body 104 of device 100 at or near the distal
end of device 100. Various embodiments of device 100 as described
herein may comprise two or more sensors 102, and sensors 102 may be
positioned along various portions of body 104 of device 100.
Additionally, device 100 may comprise any number of suitable
devices 100 with the characteristics/components described herein,
which may include, but are not limited to, catheters and
guidewires. For example, device 100 may comprise a standard
catheter, a balloon catheter, an angioplasty catheter, a
fluid-filled silastic pressure-monitoring catheter, a standard
wire, an impedance wire, a guidewire, and other catheters or wires
that may include the characteristics of a device 100 as described
herein.
[0040] In the embodiment shown in FIG. 1, sensors 102 are separated
by a distance L as shown therein. As discussed in greater detail
herein, an exemplary method for determining FFR is based upon the
principle that two or more sensors 102 spaced at a predetermined
distance apart can "time" the injection of a bolus injection as the
plug flow moves past the sensors 102 sequentially (e.g., sensor 102
"1" first, and then sensor 102 "2" as shown in FIG. 1). Upon
detection of the bolus by sensors 102 in accordance with the
present application, a determination of flow velocity may be
determined based upon the distance between the two sensors 102 (L)
and the time difference between the detection of the bolus by
sensors 102. As previously referenced herein, such a bolus may
include and/or comprise one or more indicators (e.g., a
hyper-osmotic solution, a hypo-osmotic solution, a solution of a pH
different from the native fluid flowing within the target vessel, a
solution of a different temperature than the native fluid flowing
within the target vessel, etc.) detectable by sensors 102 (e.g.,
detection electrodes, pH sensors, thermocouples, etc.) positioned
along the body 104 of device 100, so that the indicator(s), when
introduced to a vessel containing device 100, are detectable at
various times by the sensor(s) 102 positioned along device 100.
[0041] In at least one embodiment of a method for determining FFR,
a device 100 comprising two or more sensors 102 is useful for
performing said method. An exemplary method of the disclosure of
the present application comprises the steps of inserting such a
device 100 into a vessel with a fluid flow and
injecting/introducing a bolus (either from said device 100 or
another device) which can be detected by sensors 102. In at least
one embodiment of a method 600 for determining FFR of the present
disclosure, and as shown in the block diagram of FIG. 6, method 600
comprises the step of positioning a device 100 comprising at least
two sensors 102 within a vessel or organ (positioning step 602),
wherein the at least two sensors 102 are separated a known distance
from one another. Such a method 604 further comprises the steps of
detecting at least one parameter of a first fluid within the vessel
or organ using sensors 102 (first detection step 604), and
injecting a second fluid having at least one parameter different
than the at least one parameter of the first fluid into the vessel
or organ to temporarily displace the first fluid at the site of
injection (injection step 606). An exemplary method 600 of the
present disclosure further comprises the steps of detecting at
least the different parameter of the second fluid by sensors 102
(second detection step 608) and measuring the time of detection of
the second fluid by each of the at least two sensors 102 (measuring
step 610). An exemplary method 600 may further comprise the step of
determining flow velocity of the second fluid within the vessel or
organ based upon the time of detection of the second fluid by each
of the at least two sensors 102 (flow velocity determination step
612). An additional exemplary method 600 of the present disclosure
may further comprise the step of determining FFR based upon
volumetric flow and a cross-sectional area of the vessel or organ
(FFR determination step 614) as described in further detail
herein.
[0042] An exemplary embodiment of at least a portion of a device
useful for determining FFR using impedance is shown in FIG. 2. As
shown the exemplary embodiment in FIG. 2, device 200 comprises at
least one pair of excitation electrodes 202 (each excitation
electrode 202 labeled "E" in FIG. 2) and at least two pairs of
detection electrodes 204 (each pair of detection electrodes 204
labeled "D" in FIG. 2) positioned along the body 206 of device 200
at or near the distal end of device 200. Such an arrangement of
three pairs of electrodes (one pair of excitation electrodes 202
and two pairs of detection electrodes 204) is referred to herein as
a "hexa-polar" arrangement. Excitation electrodes 202, when
activated, provide an electric field (not shown) between the
excitation electrodes 202 so that detection electrodes 204, when
activated, may detect the electric field.
[0043] Additional devices other than at least the portion of device
200 shown in FIG. 2 are also considered to be within the scope of
the present application. For example, an exemplary device 200 may
comprise more electrodes than the hexa-polar arrangement of
electrodes shown in FIG. 2. For example, additional exemplary
devices 200 may contain one pair of excitation electrodes 202 and
three pairs of detection electrodes 204, and may further include
devices 200 containing two pairs of detection electrodes 202 spaced
a distance apart from one another so not to interfere with the
excitation field of each pair of detection electrodes 202, whereby
each of the two pairs of excitation electrodes 202 has at least one
pair of detection electrodes 204 positioned therebetween. In at
least one exemplary embodiment of a device 200 of the present
disclosure, device 200 comprises one pair of excitation electrodes
202 and five pairs of detection electrodes 204 spaced known
distance(s) apart from one another.
[0044] As referenced above, detection electrodes 204 operate to
detect a electric field generated by a pair of excitation
electrodes 202, and therefore, at least one pair of detection
electrodes 204 must be positioned in between the pair of excitation
electrodes 202 in order to properly detect the field as referenced
herein. Accordingly, and for example, an additional embodiment of a
device 200 comprising one pair of excitation electrodes 202 and
three pairs of detection electrodes 204 positioned therebetween
would allow for three separate field detections, namely one
detection by each of the three pairs of detection electrodes
204.
[0045] An embodiment of a device 200 comprising two pairs of
excitation electrodes 202 and a pair of detection electrodes 204
positioned between each pair of excitation electrodes 202 would
allow each pair of detection electrodes 204 to each detect a field
generated by each pair of excitation electrodes 202. The various
embodiments referenced herein are merely exemplary embodiments of
devices 200 of the disclosure of the present application, and other
embodiments of devices 200 are hereby contemplated within the
disclosure of the present application.
[0046] Additionally, device 200 may comprise any number of suitable
devices 200 with the characteristics/components described herein,
which may include, but are not limited to, catheters and
guidewires. For example, device 200 may comprise a standard
catheter, a balloon catheter, an angioplasty catheter, a
fluid-filled silastic pressure-monitoring catheter, a standard
wire, an impedance wire, a guidewire, and other catheters or wires
that may include the characteristics of a device 200 as described
herein.
[0047] Devices 100, 200 of the present disclosure may be part of a
system 500 as shown in the exemplary block diagram embodiment of a
system for determining FFR using impedance of the present
disclosure shown in FIG. 5. As shown in FIG. 5, system 500
comprises device 100, 200 (or other devices in accordance with the
present application) and a data acquisition and processing system
502 in communication with the device 100, 200, wherein the data
acquisition and processing system 502 is operable to calculate flow
velocity of a fluid based upon the detection of the fluid within a
vessel or organ by the sensors 102 coupled to device 100 or the
detection electrodes 204 coupled to device 200. An exemplary data
acquisition and processing system 502 may comprise, for example, a
computer or another electronic device capable of receiving data
from sensors 102 or detection electrodes 204 and processing such
data to determine flow velocity, volumetric flow, and/or FFR.
[0048] In at least one embodiment of a method for determining FFR
using impedance, a device 200 comprising multiple excitation
electrodes 202 and detection electrodes 204 is useful for
performing said method. An exemplary method of the disclosure of
the present application comprises the steps of inserting such a
device 200 into a vessel with a fluid flow and injecting a bolus
(either from said device 200 or another device) which can be
detected by the detection electrodes 204.
[0049] In at least one embodiment of a method 700 for determining
FFR using impedance of the present disclosure, as as shown in the
block diagram of FIG. 7, method 700 comprises the steps of
positioning a device 200 comprising excitation electrodes 202 and
at least two pairs of detection electrodes 204 within a vessel or
organ (positioning step 702), wherein the at least two pairs of
detection electrodes 204 are separated a known distance from one
another. The excitation electrodes 202 may then be activated to
generate an electric field detectable by the detection electrodes
204 (field generation step 704). Such a method 700 further
comprises the steps of detecting the conductance of a first fluid
having a first conductivity within the vessel or organ using the
detection electrodes 204 (first conductance detection step 706),
and injecting a second fluid having a second conductivity into the
vessel or organ to temporarily displace the first fluid at the site
of injection (injection step 708). An exemplary method 700 of the
present disclosure further comprises the steps of detecting the
conductance of the second fluid by the at least two pairs of
detection electrodes 204 (second conductance detection step 710)
and measuring the time of conductance detection by each of the at
least two pairs of detection electrodes 204 (measuring step 712).
An exemplary method 700 may further comprise the step of
determining flow velocity of the second fluid within the vessel or
organ based upon the time of conductance detection by each of the
at least two pairs of detection electrodes 204 (flow velocity
detection step 714). An additional exemplary method 700 of the
present disclosure may further comprise the step of determining FFR
based upon volumetric flow and a cross-sectional area of the vessel
or organ (FFR determination step 716) as described in further
detail herein.
[0050] Such a method is based upon the principle that two sensors
spaced at some distance apart (for example, the two pairs of
detection electrodes 204 separated by a distance L as shown in FIG.
2), can time the injection of a bolus injection as the plug flow
moves past the two sensors sequentially. Upon detection of the
bolus by the two pairs of detection electrodes 204 in accordance
with the present disclosure, a determination of flow velocity may
be determined based upon the distance between the two detection
electrodes 204, L, and the time difference between the detection of
the bolus by the two pairs of detection electrodes 204.
[0051] The use of either hyper-osmotic or hypo-osmotic solution can
be detected by detection electrodes 204 as shown in FIGS. 3A and
3B, respectively. If, in accordance with the disclosure of the
present application, one combines this detection concept with a
hexa-polar arrangement of electrodes (as shown in FIG. 2, for
example) with a single injection of either a hyper-osmotic solution
or a hypo-osmotic solution (or saline, for example, as shown in
FIG. 3A), the sequential detection of the saline solution can be
made by the two sets of detection electrodes 204 (labeled as "1"
and "2" in FIG. 2). Accordingly, the time (t) interval between the
passing bolus can be determined as the difference between the times
detected at the two separate positions:
.DELTA.t=t.sub.2-t.sub.1 [1]
[0052] Hence, the velocity, V, of the bolus is given by the
following formula:
V=L/.DELTA.t [2]
[0053] wherein L is the length between the sensors, and the
volumetric flow is as follows:
Q=V*CSA [3]
[0054] where cross-sectional area, CSA, may be determined using any
number of suitable methods and/or devices for performing the
same.
[0055] The equation governing the physics of electrical conductance
in a blood vessel is given by:
G ( t ) = C S A ( t ) .sigma. L + G p ( t ) [ 4 ] ##EQU00001##
[0056] wherein G (the conductance) is the ratio of the current
induced by the excitation electrodes 202 and the potential
difference between the detection electrodes 204, CSA is the
cross-sectional area of a vessel, a is the specific conductivity of
the fluid, L is the distance between detection electrodes 204,
G.sub.p is an offset error resulting from current leakage and is
the effective parallel conductance of the structure outside the
vessel lumen (vessel wall and surrounding tissue), and t is the
time in the cardiac cycle.
[0057] If the following is considered:
G p = .gamma. C S A .sigma. L [ 5 ] ##EQU00002##
[0058] wherein .gamma. is a constant, Equation [4] can be expressed
as
G = I .DELTA. V = C S A .sigma. L ( 1 + .gamma. ) [ 6 ]
##EQU00003##
[0059] wherein I is the current through electrodes 1 and 4 (as
shown in FIG. 2, for example), and .DELTA.V is the voltage drop.
The electric resistance in a blood vessel, R, is given by:
R = 1 G = .DELTA. V I = L C S A .sigma. ( 1 + .gamma. ) [ 7 ]
##EQU00004##
[0060] In such an embodiment, and as referenced above, excitation
electrodes 202 (electrodes numbered "1" and "4" in FIG. 2) create
the field and also serve to simultaneously detect the various fluid
parameters as referenced herein.
[0061] In order to calculate the flow rate/velocity using devices
100, 200 of the present disclosure, a solution (such as saline, for
example) is infused into the vessel lumen over sensor 100
positioned along device 100 or detection electrodes 204 positioned
along device 200 as previously referenced therein. Pairs of
excitation electrodes 202, in at least one embodiment, are used as
detectors since they are spaced further apart relative to detection
electrodes 204, therefore providing a more accurate time of
passage.
[0062] FIG. 8 shows a schematic of displacement of saline by blood
after the injection of saline. As shown in FIG. 8, the grey and
black plots represent the saline solution and blood in the vessel
lumen, respectively, and the dashed horizontal and vertical plots
represent the vessel wall and tissues surrounding the vessel
segments with saline solution and blood, respectively. Equation [7]
can therefore be written as follows:
.DELTA. V total I = .DELTA. V blood I + .DELTA. V saline I = L
blood CSA .sigma. blood ( 1 + .gamma. blood ) + L saline CSA
.sigma. saline ( 1 + .gamma. saline ) = L CSA .sigma. blood ( 1 +
.gamma. blood ) + L saline ( 1 CSA .sigma. saline ( 1 + .gamma.
saline ) - 1 CSA .sigma. blood ( 1 + .gamma. blood ) ) [ 8 ]
##EQU00005##
[0063] wherein .DELTA.V.sub.total is the total voltage difference
of both saline and blood interface spanning the electrodes (FIG.
8), V.sub.blood is the voltage difference of blood (right side of
FIG. 8), .DELTA.V.sub.saline is the voltage difference across
saline portion (left side of FIG. 8), L.sub.blood is the blood
segment length, L.sub.saline is the saline segment length,
.sigma..sub.blood is the specific conductivity of blood,
.sigma..sub.saline is the specific conductivity of saline,
.gamma..sub.blood is a blood constant, and .gamma..sub.saline is a
saline constant. If a constant .alpha. is defined as
.alpha. = 1 CSA .sigma. saline ( 1 + .gamma. saline ) - 1 CSA
.sigma. blood ( 1 + .gamma. blood ) [ 9 ] ##EQU00006##
[0064] then Equation [8] can be written as:
.DELTA. V total I = .DELTA. V blood only I + .alpha. L saline [ 10
] ##EQU00007##
[0065] wherein .DELTA.V.sub.blood only is the voltage drop across
the blood portion. If a constant flow rate of saline solution is
assumed to flow (transport) through the vessel lumen, then
L.sub.saline=v.DELTA.t [11]
wherein v is the mean flow velocity and .DELTA.t is the time.
Equations [9] and [10] can be combined to give:
.DELTA. t = .DELTA. V total I .alpha. v - .DELTA. V blood only I
.alpha. v [ 12 ] ##EQU00008##
[0066] wherein I, .alpha., and v are constant. Hence, a linear
relationship exists between the change in time, .DELTA.t, and the
voltage difference, .DELTA.V.sub.total. Prior to the injection of
saline solution into the vessel segment between detection
electrodes 204, L.sub.saline=0, .DELTA.t=0, and
.DELTA.V=.DELTA.V.sub.blood only. When the saline solution occupies
the vessel segment between detection electrodes 204,
L.sub.saline=L, .DELTA.t=.sub.transport, and
.DELTA.V=.DELTA.V.sub.saline only.
[0067] The slope dV/dt, determined using an exemplary device 200 of
the present application, is shown in FIG. 9 for a typical
measurement made in a swine coronary artery. FIG. 9 shows a graph
depicting the electric voltage drop across detection electrodes 204
as saline solution, for example, displaces blood present within a
vessel. A decrease in voltage, as shown in FIG. 9, implies an
increase in conductance.
[0068] As shown in FIG. 9, .DELTA.V.sub.blood only and
.DELTA.V.sub.saline only are measured using an exemplary device 200
such that
.DELTA.t.sub.transport=|.DELTA.V.sub.saline.sup.full-.DELTA.V.sub.blood.-
sup.full|/(dV/dt) [13]
[0069] wherein .DELTA.t.sub.transport is the desired .DELTA.t,
.DELTA.V.sub.full saline is the voltage drop if only saline is
present (i.e., when blood is fully displaced), and
.DELTA.V.sub.full blood is the voltage drop if only blood is
present (i.e., when blood washes out saline). After the velocity is
determined, the flow rate in the vessel segment can be calculated
according to the conservation of mass, namely
Q=CS v=CS L/.DELTA.t.sub.transport [14]
[0070] wherein Q is the volumetric flow rate, and wherein CS is the
mean CSA of the profile given by the mean value theorem as:
Q = v .intg. CS A _ dx .intg. dx [ 15 ] ##EQU00009##
[0071] The integrals are evaluated over the profile between the
proximal and distal measurements.
[0072] As referenced herein, excitation electrodes 202 can measure
the time of passage of the saline injection to provide the velocity
since the spacing between the excitation electrodes 202 is known.
The basic concept is that a junction potential is created when the
blood displaces the injected saline, and this junction potential
deflection is linear is shown below. FIG. 10 shows preliminary
measurements of flow velocity in the swine coronary artery using a
flowmeter (Transonic, Inc.) and an exemplary device 200 of the
present disclosure in three animals, noting that the least-square
fit shows a linear relationship with a slope of 1.02 (a R.sup.2 of
0.955), which is highly significant. As the CSA can be determined
as referenced herein, the product of CSA and velocity yields the
desired volumetric flow rate.
[0073] A finite element model was developed to validate the linear
relationship between time .DELTA.t and voltage difference
.DELTA.V.sub.total. The equation of continuity (conservation of
electric charge) governing the distribution of electric potential,
V, is given by Poisson's equation as
.gradient. J = - .differential. .rho. .differential. t [ 16 ]
##EQU00010##
[0074] where the current density, J, is related to the electric
potential as J=-.sigma..gradient.V and .rho., .sigma., and
.gradient. are the electric volume charge density, electric
conductivity, and del operator, respectively. Equation [16]
indicates that the electric current density diverging from a small
volume per unit volume equals to the time rate of decrease of
charge per unit volume at every point. In the present control
volume, .differential..rho./.differential.t=0 except for specific
boundaries where the driving current, I, is injected and ejected
into the control volume. Therefore, Equation [16] can be simplified
as
.gradient.(.sigma..gradient.V)=-1 [17]
[0075] The Neumann boundary condition is applied to the external
boundary except for the specific boundaries with the injection and
ejection of driving current. A Galerkin finite element program was
developed to calculate the nodal electric potential as shown in the
isopotential contour plot of the electric field for a coronary
artery with blood flows shown in FIG. 10. The isopotential field
lines for a coronary artery shown in FIG. 10 simulate the
deflection of voltage when saline solution is infused into the
vessel lumen or when the saline is washed out by the blood, similar
to the experimental measurements shown in FIG. 9. Finally, the
relationship between time .DELTA.t=L.sub.2/v and voltage difference
.DELTA.V.sub.mix was determined as represented by Equation [12].
The finite element model was then used to validate the linearity
between .DELTA.t and .DELTA.V as shown in FIG. 11, which shows the
relationship between .DELTA.t and .DELTA.V and a least-square fit
of a perfect linear relationship (R.sup.2=1).
[0076] The flow rate may also be determined as follows. If the
electrodes of an exemplary device 200 of the present disclosure are
referred to as 1, 2, 3 and 4 (as shown in FIG. 2), and as
previously referenced herein, electrodes 1 and 4 represent
excitation electrodes 202 and 2 and 3 represent detection
electrodes 204 useful for the detection for measurement of
diameter, for example. For velocity measurement, one can still
excite at 1 and 4, but detection is simultaneously capable with
1&2 and 3&4. This procedure provides two sets of
simultaneous voltage-time (or conductance-time) curves as the bolus
passes the electrodes as shown in FIG. 12. The shape of the curves
is nearly identical but there is a time lag as shown in the
figure.
[0077] The mean transit time for each curve can be calculated
according to the mean value theorem, namely
t _ = .intg. tG ( t ) dt G ( t ) [ 18 ] ##EQU00011##
[0078] wherein G(t) is the measured electrical conductance and t is
the mean transit time. The difference in mean transit time
(.DELTA.t) can then be used to calculate the mean velocity since
the distance between the electrodes travel by the fluid is known.
When the velocity is determined as referenced herein, the flow rate
in the vessel segment can be calculated according to conservation
of mass as referenced in Equation [14]. The integrals are evaluated
over the desired profile between the proximal and distal
measurements.
[0079] The FFR is defined as:
FFR = P distal - P v P a - P v [ 19 ] ##EQU00012##
[0080] wherein P.sub.a is the mean aortic pressure, P.sub..nu. is
the central venous pressure, and P.sub.distal is the hyperemic
coronary pressure distal to stenosis. If venous pressure is assumed
to be zero or remains unchanged, Equation [19] is further
simplified to:
FFR = P distal P a = P a - .DELTA. P P a [ 20 ] ##EQU00013##
[0081] wherein .DELTA.P is the pressure gradient along the axis of
vessel segment from proximal to distal portion of stenosis.
[0082] The determination of .DELTA.P from a generated lumen profile
based on conservation of momentum and energy is as follows. The
Bernoulli equation (conservation of energy) is written as:
.DELTA. P = .rho. Q 2 2 ( 1 CSA distal 2 - 1 CSA proximal 2 ) +
energy loss [ 21 ] ##EQU00014##
where CSA.sub.proximal and CSA.sub.distal are the proximal and
distal cross-sectional areas of the lumen profile obtained by an
exemplary device 200, respectively, and Q is the flow rate through
the segment as obtained above. There are two major energy losses:
diffusive energy loss and energy loss due to sudden enlargement in
area from greatest stenosis (minimum CSA) to normal (distal) vessel
segment.
[0083] Regarding diffusive energy loss, when the flow is assumed to
be fully-developed in the vessel segment, the Poiseuille formula
(conservation of momentum) is written as:
Q = - CSA 2 8 .pi..mu. dp dx [ 22 ] ##EQU00015##
[0084] wherein .mu. is the blood viscosity, and wherein dp/dx is
the pressure gradient. Equation [22] may then be rewritten as:
- dp = 8 .pi. .mu. CSA 2 Qdx [ 23 ] ##EQU00016##
[0085] wherein dx is the infinitesimal length of vessel.
Integrating Equation [23] along the axis of vessel segment
yields:
.DELTA. P viscous = .intg. 0 L total 8 .pi. .mu. CSA 2 Qdx [ 24 ]
##EQU00017##
wherein .DELTA.P.sub.vicious is the pressure drop along the axis of
vessel segment due to viscous diffusivity, and L.sub.total is the
length of the distance between proximal and distal points of the
profile as shown in FIG. 12.
[0086] The energy loss due to an abrupt expansion in area can be
calculated approximately from the one-dimensional continuity,
momentum and energy equations, which can be written as:
.DELTA. P expansion = .rho. Q 2 2 ( 1 CSA stenosis - 1 CSA distal )
2 [ 25 ] ##EQU00018##
[0087] wherein .DELTA.P expansion is the pressure drop due to an
abrupt expansion in area, and wherein CSA.sub.stenosis and
CSA.sub.distal are the cross-section areas at the stenosis and just
distal to the stenosis, respectively. When Equations [24] and [26]
are substituted into Equation [21], the following desired result is
obtained:
.DELTA. P = .rho. Q 2 2 ( 1 CSA distal 2 - 1 CSA proximal 2 ) +
.intg. 0 L total 8 .pi. .mu. CSA ( x ) 2 Qdx + .rho. Q 2 2 ( 1 CSA
stenosis - 1 CSA distal ) 2 [ 26 ] ##EQU00019##
[0088] wherein CSA.sub.distal is the cross-sectional area at the
distal end of the vessel lesion.
[0089] FIG. 13 shows a comparison of pressure drops across various
stenoses (40, 50, 60, and 70% stenosis) with different lesion
lengths (1, 2, and 3 cm) between computational results from the
finite element model based on Equation [26], which itself can be
used to determine FFR from an exemplary device 200 of the present
disclosure as has been validated by a finite element simulation
shown in FIG. 13.
[0090] Regarding data pressure and FFR measurements, if the flow
and lesion geometry are accurately known, the laws of physics
(conservation of mass and momentum) can accurately determine the
pressure drop along the stenosis. A finite element simulation of
actual blood vessel geometries was used to validate the
formulation. FIG. 13 shows excellent accuracy of the physics-based
equation (Equation [18]) which incorporates the measured flow and
lesion geometry as compared to a finite element simulation, noting
that there are no empirical parameters in this formulation, as it
is strictly the geometry and flow as determined by the devices of
the present disclosure and conservation laws of physics as
referenced herein.
[0091] The disclosure of the present application, and in at least
one embodiment, uses the premise that the injection of solution to
momentarily replace the blood does not affect the normal velocity
of flow through an organ. This principle has been previously
validated for contrast injections where the contrast power
injection only increased blood flow by less than 15%. It has been
found that an injection rate of 2-4 ml/s is substantially adequate
for complete replacement of blood with contrast for baseline and
hyperemic flow. Power injection of contrast into a coronary artery
produces a back pressure that momentarily prevents blood from
entering the coronary artery. The magnitude of the generated back
pressure depends on the injection rate, viscosity of injection, the
ratio of vascular and aortic resistance and vessel compliance.
[0092] With the various techniques disclosed herein, and in one
testing example, flow measurements were made during contrast
injection and completed within three seconds after the start of
contrast injection. An injection time of three seconds was adequate
to ensure that only undiluted contrast material was entering the
vascular bed during the flow measurement time interval. As such
injections do not require a power injector, changes in flow are
expected to be substantially less than 15%, which is a well
accepted clinical tolerance for such a procedure.
[0093] While various embodiments of devices, systems, and methods
for determining fractional flow reserve have been described in
considerable detail herein, the embodiments are merely offered by
way of non-limiting examples of the disclosure described herein. It
will therefore be understood that various changes and modifications
may be made, and equivalents may be substituted for elements
thereof, without departing from the scope of the disclosure.
Indeed, this disclosure is not intended to be exhaustive or to
limit the scope of the disclosure.
[0094] Further, in describing representative embodiments, the
disclosure may have presented a method and/or process as a
particular sequence of steps. However, to the extent that the
method or process does not rely on the particular order of steps
set forth herein, the method or process should not be limited to
the particular sequence of steps described. Other sequences of
steps may be possible. Therefore, the particular order of the steps
disclosed herein should not be construed as limitations of the
present disclosure. In addition, disclosure directed to a method
and/or process should not be limited to the performance of their
steps in the order written. Such sequences may be varied and still
remain within the scope of the present disclosure.
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