U.S. patent application number 15/807430 was filed with the patent office on 2018-03-08 for method and system for measuring pulmonary artery circulation information.
The applicant listed for this patent is PneumRx, Inc.. Invention is credited to Phillip Stephen Levin, Edmund J. Roschak, Jeffrey Schwardt.
Application Number | 20180064411 15/807430 |
Document ID | / |
Family ID | 40642693 |
Filed Date | 2018-03-08 |
United States Patent
Application |
20180064411 |
Kind Code |
A1 |
Roschak; Edmund J. ; et
al. |
March 8, 2018 |
METHOD AND SYSTEM FOR MEASURING PULMONARY ARTERY CIRCULATION
INFORMATION
Abstract
Minimally invasive systems and methods are described for
measuring pulmonary circulation information from the pulmonary
arteries. A transbronchial Doppler ultrasound catheter is advanced
through the airways and in the vicinity of the pulmonary artery.
Doppler ultrasound energy is sent through the airway wall and
across the pulmonary artery to obtain velocity information of blood
flowing through the artery. The velocity information is used to
compute pulmonary circulation information including but not limited
to flowrate.
Inventors: |
Roschak; Edmund J.; (Mission
Viejo, CA) ; Schwardt; Jeffrey; (Palo Alto, CA)
; Levin; Phillip Stephen; (Storrs, CT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PneumRx, Inc. |
Santa Clara |
CA |
US |
|
|
Family ID: |
40642693 |
Appl. No.: |
15/807430 |
Filed: |
November 8, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13571703 |
Aug 10, 2012 |
9839408 |
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15807430 |
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12272703 |
Nov 17, 2008 |
8323202 |
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13571703 |
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60988738 |
Nov 16, 2007 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 8/12 20130101; A61B
8/06 20130101; A61B 8/4483 20130101; A61B 8/488 20130101; A61B 8/04
20130101 |
International
Class: |
A61B 8/04 20060101
A61B008/04; A61B 8/08 20060101 A61B008/08; A61B 8/06 20060101
A61B008/06; A61B 8/12 20060101 A61B008/12; A61B 8/00 20060101
A61B008/00 |
Claims
1. A transbronchial method for the automated determination of an
instantaneous volume flow rate within a blood vessel of a patient,
the method comprising: processing, with a signal processing unit,
signals obtained by an ultrasound transducer of a transbronchial
catheter positioned inside an airway of a lung, the ultrasound
transducer being positioned in the vicinity of the blood vessel of
the patient; and analyzing, with a processor, the processed signals
to determine the instantaneous volume flow rate within the blood
vessel of the patient.
2. The method of claim 1, wherein the determination of the
instantaneous volume flow rate within the blood vessel of the
patient is performed without directly measuring a diameter of the
blood vessel of the patient.
3. The method of claim 1, wherein the blood vessel is a pulmonary
artery of the patient.
4. The method of claim 1, wherein the processor is integral with
the signal processing unit.
5. The method of claim 4, wherein the signal processing unit is a
Doppler signal processing unit.
6. The method of claim 1, wherein the transbronchial catheter is a
Doppler transbronchial catheter and the ultrasound transducer is a
Doppler ultrasound transducer.
7. The method of claim 1, wherein the determination of the
instantaneous volume flow rate is further based on a diametric
limit of the blood vessel that is identified using at least some of
the processed signals.
8. The method of claim 1, wherein the determination of the
instantaneous volume flow rate includes performing a summation of a
plurality of flow rates across discrete area cross sections, and at
least some of the discrete area cross sections are within the blood
vessel.
9. The method of claim 8, wherein the summation ceases when
calculations for the instantaneous volume flow rate no longer
increase in value or when a rate of increase of the instantaneous
volume flow rate falls below a predetermined threshold.
10. The method of claim 8, wherein the summation comprises a
plurality of iterations corresponding to the plurality of flow
rates, and wherein the determined instantaneous volume flow rate is
calculated in a last iteration of the plurality of iterations.
11. A medical system for determining an instantaneous volume flow
rate within a blood vessel of a patient, the system comprising: a
transbronchial catheter having an ultrasound transducer, the
ultrasound transducer configured to obtain signals when the
transbronchial catheter is positioned inside an airway of a lung of
the patient and the ultrasound transducer is positioned in the
vicinity of the blood vessel of the patient; a signal processing
unit that processes the signals obtained by the ultrasound
transducer of the transbronchial catheter, and a processor that
analyzes the processed signals to determine the instantaneous
volume flow rate within the blood vessel of the patient.
12. The system of claim 11, wherein the processor determines the
instantaneous volume flow rate within the blood vessel of the
patient without using a diameter measurement of the blood vessel of
the patient.
13. The system of claim 11, wherein the blood vessel is a pulmonary
artery of the patient.
14. The system of claim 11, wherein the processor is integral with
the signal processing unit.
15. The system of claim 14, wherein the signal processing unit is a
Doppler signal processing unit.
16. The system of claim 11, wherein the transbronchial catheter is
a Doppler transbronchial catheter and the ultrasound transducer is
a Doppler ultrasound transducer.
17. The system of claim 11, wherein the processor determines the
instantaneous volume flow rate using a diametric limit of the blood
vessel that is identified using at least some of the processed
signals.
18. The system of claim 11, wherein the processor determines the
instantaneous volume flow rate by performing a summation of a
plurality of flow rates across discrete area cross sections, and at
least some of the discrete area cross sections are within the blood
vessel.
19. The system of claim 18, wherein the processor ceases the
summation when calculations for the instantaneous volume flow rate
no longer increase in value or when a rate of increase of the
instantaneous volume flow rate falls below a predetermined
threshold.
20. The system of claim 18, wherein the summation comprises a
plurality of iterations corresponding to the plurality of flow
rates, and wherein the processor determines the instantaneous
volume flow rate based on a last iteration of the plurality of
iterations.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] The present application is a Continuation of U.S.
application Ser. No. 13/571,703 filed Aug. 10, 2012; which is a
Continuation of U.S. application Ser. No. 12/272,703 filed Nov. 17,
2008 (now U.S. Pat. No. 8,323,202); which claims priority to U.S.
Provisional Application Ser. No. 60/988,738 filed Nov. 16, 2007;
the full disclosures which are incorporated herein by reference in
their entirety for all purposes.
BACKGROUND OF THE INVENTION
[0002] It is well established that assessing pulmonary arterial
pressure (PAP) is useful in diagnosing pulmonary disease such as
pulmonary hypertension. PAP, however, may remain relatively
unchanged following clinical treatment to address pulmonary
hypertension. Thus, while useful as an indicator of the presence of
pulmonary disease, PAP alone may not be practical for evaluating
improvement and patient response to treatment. For this reason,
additional pulmonary circulation information is desired.
[0003] Total pulmonary vascular resistance (TPR) provides
information about the flowrate and pressure in the pulmonary
vasculature. TPR is a ratio of the PAP to flowrate. Unlike PAP, TPR
changes to some degree in response to treatment and can therefore
be used to help assess the efficacy or degree of the treatment
effect that eventually results in patient improvement.
[0004] Various approaches are available to obtain pulmonary
information. For example, a passive approach is disclosed in Patent
Pub. No. 2001/0039383 to Mohler. In this application, a sensor
assembly is provided that detects heart sounds. The sensor is
placed in contact with the skin, and is connected with a signal
processing means. Pressure information is measured based on
acoustic wave signatures arising from the heart. See also U.S. Pat.
No. 6,368,283 to Xu et al.
[0005] A more invasive approach involves implanting a medical
device for sensing the absolute and barometric pressures as
disclosed in U.S. Pat. No. 6,024,704 to Meador et al. The
implantable sensor described in Meador includes two leads. One lead
is positioned in the subcutaneous layer of the skin for measuring
the barometric pressure and a second lead is positioned in the
right ventricle of the heart for measuring pressure therein. The
contents of the above teachings are incorporated by reference in
their entirety and may be optionally combined with the methods and
devices described herein.
[0006] Despite the results of the above mentioned measurement
techniques, an invasive catheterization procedure is still
considered by many physicians to be the gold standard to confirm
pulmonary hypertension and for determining the PAP. In a right
heart catheterization, a catheter is inserted through the pulmonary
arteries and into the right ventricle of the heart. Once positioned
in the right ventricle, the pulmonary pressure is measured directly
using a pressure sensor. However, this procedure requires
penetration of the vasculature, and requires significant surgical
intervention. As such, the procedure carries an undesirable amount
of inconvenience, cost, and risk to the patient.
[0007] A more convenient, less invasive approach is desired for
obtaining accurate pulmonary circulation information.
SUMMARY OF THE INVENTION
[0008] Minimally invasive systems and methods are described for
measuring pulmonary circulation information from the pulmonary
arteries.
[0009] Variations of the medical systems for measuring pulmonary
circulation information of the pulmonary artery include a catheter
comprising at least one ultrasonic transducer, and an ultrasound
Doppler signal processing unit for processing signals sent by and
received from the transducer. The system can also include a
processor or processor means for analyzing the Doppler signals to
perform the analysis of the pulmonary circulation information
disclosed herein. In such a case, the processor or processor means
can include a typical microprocessor based device that is either
discrete from or integral with the Doppler signal processing unit.
The system can also include a visual indicator. The visual
indicator can be located on either the face of the control unit or
the processor. Alternatively, or in combination, the visual
indicator can transmit signals to another monitor (such as those
used with a bronchoscope) so that information can be displayed on
the monitor and observed by the physician during the procedure.
[0010] In one variation, the system includes catheters having
designs suited for obtaining anatomic information or arterial flow
related information. For example, a number of transducers may be
located at various angles with respect to an axis of the catheter.
In another variation, the transducer(s) can rotate or move within
the catheter.
[0011] The system can also include a data set of predetermined
waveforms obtained by and associated with direct measurement of
pulmonary arterial pressure. The data set is used to compare a
real-time or other measured pressure signature to one or more of
the predetermined waveforms to determine an estimated mean arterial
pressure or other pulmonary circulation information. This
predetermined data set can be stored within memory means that is
integrated with the controller or processor. Alternatively, the
data set can be provided to the system via a removable means of
data storage. Examples of such memory means are commonly known.
[0012] The present invention also includes methods for determining
pulmonary circulation information in a pulmonary artery without
puncturing or opening the pulmonary artery. The methods include
providing an ultrasound Doppler catheter, said catheter comprising
a distal section and at least one ultrasound transducer in said
distal section, advancing said distal section of said ultrasound
Doppler catheter through a natural respiratory opening, and into an
airway and to a location along an airway wall such that at least a
portion of said distal section and said at least one ultrasound
transducer is in proximity of the pulmonary artery, sending and
receiving ultrasonic waves to said pulmonary artery from said
ultrasound transducer; determining a measured pressure signature by
analyzing the received ultrasonic waves, and comparing the measured
pressure signature to one or more predetermined pressure signatures
wherein each of said predetermined pressure signatures has an
associated mean pulmonary arterial pressure.
[0013] The present invention also includes a method for determining
flowrate in a blood vessel comprising determining velocity profiles
across the blood vessel and computing the flowrate based on said
velocity profiles.
[0014] The description, objects and advantages of the present
invention will become apparent from the derailed description to
follow, together with the accompanying drawings. The invention
includes any number of combination of method and devices, or
aspects of such methods and devices where such combinations are
possible.
[0015] The disclosure and invention specifically include
combination of features of various embodiments as well as
combinations of the various embodiments where possible.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is an illustration of a catheter system in accordance
with the present invention.
[0017] FIG. 2 is an anterior view of a catheter positioned in the
bronchi and in the vicinity of a pulmonary artery.
[0018] FIG. 3 is an enlarged view of a catheter distal end in
accordance with one embodiment of the present invention.
[0019] FIG. 4 is an enlarged view of a catheter distal end
comprising a plurality of ultrasonic transducers.
[0020] FIG. 5 is an enlarged view of a catheter distal end
comprising another embodiment of the present invention.
[0021] FIG. 6 is an illustration of an ultrasound Doppler probe
positioned within an airway and sending a beam through the airway
wall and across a blood vessel.
[0022] FIG. 7 is a plot of a velocity profile across a blood vessel
as a function of distance from the Doppler probe in accordance with
the present invention.
[0023] FIG. 8 is an illustration of an ultrasound Doppler probe
within an airway and sending a beam through the blood vessel
wherein the probe is positioned at an angle to the blood
vessel.
[0024] FIG. 9a is an illustration of a tissue region divided into a
plurality of discrete sub-sections.
[0025] FIG. 9b is a plot of a velocity profile across the tissue
region illustrated in FIG. 9a.
[0026] FIG. 10 is a plot of velocity profiles measured at different
times.
[0027] FIG. 11 is a plot of a flowrate calculated over a time
duration in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0028] Novel systems and methods to determine pulmonary circulation
information are described herein. In particular, the systems and
method can include minimally invasive approaches to determine
pulmonary circulation information. In one variation, a
transbronchial or bronchoscopic approach is described that measures
pulmonary pressure and volumetric flowrate of the fluid in the
pulmonary artery. The described system is capable of measuring
various indicia of pulmonary circulation information without the
need or requirement to penetrate the arterial wall or otherwise
enter the vasculature. In additional variations, the systems
described herein can be combined with conventional measurement
modes for improved assessment of pulmonary circulation.
[0029] FIG. 1 illustrates a catheter system in accordance with one
embodiment of the present invention. System 10 includes a Doppler
ultrasound catheter 20 and a signal processing unit 30. The
processing unit 30 can also include a processor or processor means
for analyzing the Doppler signals to perform the analysis of the
pulmonary circulation information disclosed herein. Alternatively,
the processor means may be a separate component. However, such a
processor can be incorporated together with the Doppler processing
unit 30.
[0030] FIG. 1 also illustrates the processing unit 30 as including
a visual indicator 34 or display. In additional variations, the
visual indicator 34 can comprise a signal generated by the system
that causes visual information or other data to be displayed on a
monitor coupled to the bronchoscope.
[0031] The catheter 20 includes a flexible shaft and a distal
working end section. The distal section comprises an ultrasound
transducer 40 that is electrically coupled to the signal processing
unit (SPU) 30. As will be discussed further below, Doppler
ultrasound analysis is carried out to identify and determine
various attributes of the pulmonary blood flow such as flowrate and
pressure. However, other non-invasive imaging or measurement
modalities can be used with the principles of the invention such
as, for example, laser Doppler.
[0032] One application of the above mentioned system is shown in
FIG. 2. In particular, the ultrasound catheter 20 extends through
the trachea and into the left bronchi 50. The end of the catheter
is shown behind or posterior to the pulmonary artery 60. As shown,
the catheter can extend independently in the airways. However, the
present invention may be carried out with the use of a bronchoscope
or other guiding sheath, where the catheter may be extended through
the bronchoscope or guiding sheath. A bronchoscope provides an
additional mechanism to view the procedure.
[0033] FIG. 3 illustrates the distal end section of catheter 20
within bronchi 50 and in the vicinity of the pulmonary artery 60.
The tip is shown in contact with the airway wall. Once positioned
at a location along the airway, and in the vicinity of the
pulmonary artery 60, various circulation information of the
pulmonary artery may be determined such as, but not limited to: the
arterial pressure, blood-flow velocity, arterial diameter and
cross-sectional area, blood flowrate, cardiac output, and total
pulmonary resistance (TPR). The entire blood-flow velocity waveform
in response to right ventricle contraction and filling may also be
collected.
[0034] Pulmonary Arterial Pressure
[0035] Pulmonary arterial pressure (PAP) may be determined by
various techniques including without limitation ultrasound waveform
analysis. Ultrasound waveform analysis is carried out by sending
and receiving ultrasound waves from the ultrasonic transducer 40
and relies on a Doppler Effect measurement to obtain flow-rate
waveforms. The measurements may occur over a duration of time or
over a number of heart beats. The actual waveform characteristics
are then compared to known (or predetermined) waveform information.
For example, the waveform characteristics of healthy and diseased
individuals can be established as baselines. In practice, the
measured flow pattern is then compared to the base waveforms of
healthy and diseased patients to assess whether a flow pattern
indicates pulmonary hypertension.
[0036] Method of non-invasively determining pulmonary hypertension
by Doppler or other means are discussed in Non-Invasive Evaluation
of Pulmonary Hypertension by a Pulsed Doppler technique by A.
Kitabatake (Circulation 1983; 68; 302-309). However, these
techniques require visualization from outside the body. Moreover,
such external imaging of COPD patients is difficult in view of the
large amount of air trapped within hyper-inflated lungs. More
direct measuring of characteristics of blood pressure and assessing
pulmonary hypertension from within an airway under the present
invention overcomes these problems. For COPD patients, the method
of the present invention may be used to capture waveforms that
might be unobtainable using the transthoracic technique described
by Kitabatake.
[0037] As noted above, the precursor (or actual, or measured)
pressure signature is compared to a set of predetermined (or
baseline) waveforms, each of which corresponds to a specific mPAP.
The database is preferably created by comparing characteristics of
collected waveforms to pressure measurements obtained by a
traditional standard such as the right heart catheterization.
Preferably, the database includes a range of predetermined
waveforms correlated to mean pulmonary pressures from 10 to 80
mmHg, with standard of deviation of 5. If the physician determines
treatment is necessary, the physician can administer the
appropriate treatment (e.g., surgical intervention, drugs, etc.).
The physician can then assess the effects of such treatment by
obtaining an additional pressure or waveform signatures.
[0038] A waveform analysis process is further described in commonly
assigned Provisional application No. 60/944,730, filed Jun. 18,
2007, and entitled MEASUREMENT OF PULMONARY HYPERTENSION FROM
WITHIN THE AIRWAYS, the entirety of which is incorporated by
reference.
[0039] As indicated above, total pulmonary vascular resistance
(TPR) is another useful calculation for the physician. TPR is a
ratio of the pulmonary artery pressure to the cardiac output,
namely, volumetric flowrate (Q). Hence, the flowrate must be
determined in order to determine TPR.
[0040] Pulmonary Arterial Flowrate
[0041] Flowrate may be determined using a number of different
approaches. A first approach obtains flowrate (Q) by determining
the velocity, and the cross sectional area, and multiplying the two
numbers according to the equation
Q=V.times.A, where A is cross sectional area and V is average
velocity within that cross sectional area.
[0042] Velocity (V) may be calculated using Doppler shifting
analysis with the Doppler catheter system described above. A series
of ultrasound waves are delivered from transducer 40, reflected off
moving objects (namely, blood cells, micro-bubbles, or the like) in
the fluid. These reflected waves or signals are sampled at a series
of intervals corresponding to. round trip transit times between the
transducer 40 and the various sample volumes within the blood
vessel. The blood flow velocity of each sample volume can then be
determined by detecting the Doppler frequency shift of the
transmitted signal using well known techniques.
[0043] The direction of blood flow can be determined using two
reference ultrasound signals that are generated at 90 degrees out
of phase with each other. Utilizing such techniques it is possible
to map a one dimensional velocity profile by establishing a number
of individual range gates and spanning the diameter of the blood
vessel in which the transducer is positioned. There are a number of
intravascular examples of this type of measurement such as that
described in U.S. Pat. Nos. 5,339,816 and 4,856,529 (each of which
is incorporated by reference).
[0044] The cross-sectional area (A) is proportional to the square
of the diameter of the vessel. In particular,
A=.pi..times.D.sup.2/4. Consequently, in this embodiment of the
invention, the diameter (D) or radius is measured or estimated in
order to determine A.
[0045] The vessel diameter (D) can be determined utilizing
automatic diameter detection system of the type well known to those
skilled in the art. For example, U.S. Pat. No. 4,856,529 describes
a system which provides dynamic range-gating and diameter detection
utilizing Doppler shifted ultrasonic power within three sample
gates. The gates correspond to one centered on the distal vessel
wall, one near the vessel wall and one within the center of the
vessel. A feedback loop adjusts gate positions so that reflected
Doppler power from the far wall is a preset fraction of the Doppler
power obtained from a sample volume located entirely within the
central vessel lumen. The vessel diameter is then determined by
continuously detecting the delay transit time to the far sample
gate as it is adjusted to remain centered on the far wall.
Instantaneous flow is calculated from the instantaneous space
average velocity and instantaneous diameter using formulas well
known to those skilled in the art.
[0046] Another technique for measuring the diameter is based oil a
time of flight analysis and is described in, for example, U.S. Pat.
No. 5,078,148 to Nassi et al. Still other techniques may be
employed to measure the diameter and cross-sectional area of the
blood vessel and the invention is intended only to be limited to
the appended claims.
[0047] One complexity in analyzing the Doppler time of flight data
is compensating for the angle of the ultrasound waves relative to
the vessel all or fluid flow. In particular, with reference to FIG.
3, the direction of propagation of the ultrasound waves may be at
an angle (B) to the diameter (D). In the event the ultrasound
pulses and waves propagate through the fluid at an angle (B), the
diameter may be estimated larger than its actual value. It is
therefore useful to estimate or identify the angle (B) and
compensate for an increase or decrease in measured distances.
[0048] One technique for estimating the angle (B) is illustrated in
FIG. 3. The catheter 20 comprises a single transducer 40. The
distal section and transducer 40 may be extended out of a
bronchoscope and articulated against the airway wall at a
particular angle such as 0, 45, or 90 degrees. In this manner. the
angle is ascertained. This angle may be used in combination with
the Doppler ultrasound shifting and time of flight information to
identify D, A, and V. Alternatively, the catheter distal end may
include a mechanical feature or characteristic that repeatably
orients the catheter tip at a known angle to blood flow. For
example, a pre-existing bend in the distal section can necessarily
form a certain angle (A) with the vessel wall. Additionally, a
corkscrew shaped distal end, or S-bend shape may reliably locate
the transducer in a predictable location and orientation within the
airway 50 lumen.
[0049] Another embodiment is shown in FIG. 4. In the embodiment in
FIG. 4, catheter 20 includes a plurality of transducers 42, 44, and
46, each at a fixed angle. Because the angles of the transducers
are known, the time of flight ultrasound data can be adjusted to
compensate for the angle of the pulmonary artery (or other blood
vessel) 60 or catheter. Alternatively, the two or more transducers
of FIG. 4 may be utilized to capture Doppler shifted data at more
than one angle of incidence to the blood flow. The absolute blood
velocity may then be calculated by mathematically eliminating the
variable of angle of incidence, as is well known in the art and
described, for example, in U.S. Pat. No. 5,339,816.
[0050] Another embodiment is shown in FIG. 5. In the embodiment in
FIG. 5, catheter 20 is placed flush against the airway wall.
Because the transducer is fixed relative to the catheter, the
primary direction of propagation of the ultrasound waves is known.
As shown, a single transducer 52 sends signals laterally from the
distal section. The signals are perpendicular to the direction of
fluid flow. Hence, the direction of the ultrasound waves are in the
same direction as the diameter D.
[0051] Clearly, any of the above systems can also employ various
sensing mechanisms to ensure proper contact of the catheter against
an airway wall (e.g., establishing an electrical circuit,
temperature measurement, ultrasound measurement, etc.)
[0052] Another embodiment, not shown, includes a single transducer
in the distal section of the catheter. The catheter end section, or
transducer itself, is rotated or moved. Information at each
location and angle is recorded. A comparison of the sensed
information identifies a range of potential dimensions of the
diameter. An estimate may then be made in view of the range. For
example, the mean may be taken as the closest value to the actual
diameter. Or, a weighted average may be made. An example of a
rotation technique is described in U.S. Pat. No. 5,623,930.
[0053] Another approach for determining flowrate (Q) includes
evaluating velocity profiles over time and across a vessel.
Notably, it has been found that flowrate may be obtained without
directly measuring the cross-sectional area of the vessel. This
novel technique is described below.
[0054] One embodiment includes providing a pulsed wave ultrasound
Doppler probe and pulsed-wave ultrasound Doppler processing unit
(e.g. UVP Duo, manufactured by Met-Flow, Laussane, Switzerland).
The Doppler probe includes at least one ultrasound transducer. The
Doppler probe is advanced through an endoscope or bronchoscope
towards an intra-bronchial site in either the right or left main
bronchus, preferably at a position 0-20 mm distal to the carina.
The ultrasound transducer is positioned such that its beam is
directed at an angle other than perpendicular to the axis of the
vessel (a beam directed exactly 90 degrees would fail to detect a
Doppler shift). The beam width is preferably less than the blood
vessel diameter.
[0055] Referring to FIG. 6, a pulsed wave ultrasound Doppler probe
100 involves sending an ultrasound beam 110 across a blood vessel
120. Analysis of reflected ultrasound energy is performed by a
signal processor (not shown) of sample volumes 130 positioned
sequentially along the path of the ultrasound beam. Preferably at
least two, and more preferably at least 3 sampling volumes ought to
be positioned along the blood vessel diameter. Stated another way,
the length of the sampling volume is preferably less than 1/2 of
the vessel diameter. Non-limiting examples of sample volume length
range from about 1 to 3 mm, or less.
[0056] In this embodiment, the sampling range (i.e. the distance
over which the sampling volumes extend along the beam axis) is
greater than the blood vessel diameter, and includes sampling
volumes outside the blood vessel. Preferably, the range of sample
volumes extends beyond both sides of the blood vessel--from the
near or proximal side of the blood vessel, and to the far or distal
side of the blood vessel relative to the Doppler transducer. In
certain cases in which the flow profile is symmetrical about the
vessel axis this method may also be utilized successfully where the
range extends from some position within the blood vessel that is
proximal to the center of the blood vessel to some position outside
the blood vessel, distally. Similarly, the method can be utilized
successfully where the range extends from some position proximal to
the blood vessel to some position within the blood vessel that is
distal to the center of the blood vessel. A non-limiting example of
a sampling range includes at least 2 mm and more preferably between
about 2 and 20 mm.
[0057] A temporal sampling rate is a rate to collect a plurality of
instantaneous velocity profiles within a period of time. An
illustration of a velocity profile is shown in FIG. 7, and
corresponds to the set up shown in FIG. 6. The temporal sampling
rate is preferably great enough to collect a sufficient number of
instantaneous velocity profiles during each cardiac cycle, such
that the time-averaged volume flow from these profiles is an
accurate estimate of real volume flow. The temporal sampling rate
is preferably at least twice (2.times.) that of the heart rate and
is preferably as great as practicable so that the time variation of
the flow velocity can be resolved within a heart beat and from
heart beat to heart beat. Human heart rates are typically 60 to 120
beats per minute or 1-2 Hz. A non-limiting example sampling rate is
between 5 and 20 samples/second.
[0058] The sampling period is the time to collect one sample
velocity profile. The sampling period is the inverse of the
sampling rate. Non-limiting examples of the sampling period is
between 0.05 to 0.2 seconds/sample.
[0059] The sampling duration is the length of time during which
sequential velocity profiles are captured and stored. It is
preferably at least as long as a single heart beat and preferably
is at least as long as several heartbeats.
[0060] The preferred time duration for sampling will be a function
of the stability (i.e. repeatability) of the flow characteristics
of the heart beat. For example, in the case of regular heart beat,
a time duration of fewer than 10 consecutive heart beats is
adequate. Nonlimiting examples of a time duration is between 2 and
20 seconds and more preferably between 6 and 10 seconds.
[0061] In an application, a large blood vessel is located by
probing the bronchial airway walls with an ultrasound Doppler
probe. A fluid velocity profile is continuously monitored using a
Doppler processing unit. The fluid velocity profile may be shown on
a display. An adjacent blood vessel is indicated by the observation
of a time varying velocity waveform with a typical oscillating flow
waveform, characteristic of pulsatile flow in a blood vessel.
Confirmation is accomplished by observing the velocity curve with a
central peak that decays spatially to approximately zero over a
span of several millimeters. An example of such a velocity waveform
with central peak is shown in FIG. 7. The velocity profile may
consist wholly or in part of one or more negative flow regions.
Negative flow, as defined here, corresponds to flow reversal with
respect to positive flow. Flow reversal is typical of the temporal
flow pattern of an artery within a living body, as is well known in
the art. The designations "positive" and "negative" flow, as
depicted herein, will be understood to depend upon the orientation
of the ultrasound probe relative to the blood vessel under
measurement.
[0062] Once the blood vessel to be monitored has been located, the
instantaneous volume flow rate q(t) is determined. Instantaneous
volume flow rate is determined by measuring and summing a plurality
of flow rates (e.g., Vol.sub.N of FIG. 9a) across discrete area
cross sections of the blood vessel. The approximate center of the
blood vessel is computationally determined by examination of the
instantaneous velocity profile data--the locations of peak
velocities for several profiles are averaged to approximate the
center of the blood vessel.
[0063] Velocity at positions along the diameter of the vessel are
detected using Doppler shift measurements, adjusted to account for
the angle of the Doppler probe relative to the normal vector to the
vessel. As illustrated in FIG. 8, the velocity of fluid traveling
axially is equal to v'/sin(theta), where v' is the velocity
measured along the angle theta. Theta may be determined as set
forth above, or for example, as described in U.S. Pat. No.
4,103,679 (e.g., see column 4, lines 35-60), which is incorporated
by reference in its entirety.
[0064] The calculation of instantaneous volume flow rate q(t) is
iterative. To start the calculation, a first diameter is
assumed--this may be equal to the length of one or two sample
volume lengths (e.g., about 0.1 to 2 mm). This first diameter
d.sub.0 is centered over the approximate blood vessel axis (e.g.,
the spatial location where the velocity is highest) and is equal to
the adjusted length of one or two pulsed wave ultrasound Doppler
sampling volumes. Volumetric flow is calculated across this
circular area defined by the following formula:
q.sub.0(t)=u.sub.0*pi*d.sub.0.sup.2/4
[0065] where
[0066] q.sub.0(t)=instantaneous volume flow rate across a defined
circular area,
[0067] u.sub.0=measured fluid velocity across defined circular
cross section, and
[0068] d.sub.0=assumed diameter.
[0069] The instantaneous volume flow is then calculated by adding
the volume flow calculations across successively larger annular
areas, according to the following:
q.sub.n(t)=q.sub.0+.SIGMA.u.sub.n*pi*(d.sub.n.sup.2-d.sup.2.sub.n-1)/4
[0070] The velocity u.sub.n is the average of the velocities of the
multiple sampling volumes that cross the annular area for each
iteration n (see FIGS. 9a and 9b). This summation continues until
subsequent calculations of q.sub.n(t) no longer increase or the
rate of increase is below a predetermined threshold, indicating
that the Doppler sampling volumes are no longer within the vessel
of interest. The value of q.sub.n(t) calculated in the last
iteration is the instantaneous volume flowrate, q(t), calculated
without the need to directly measure vessel diameter.
[0071] Volume flowrate calculated in this manner is accurate and
free of errors associated with poor estimates of vessel diameter,
or temporal variations in vessel diameter that are known to occur
due to the compliant nature of arteries and veins. The number of
iterations necessary in this step is determined by the mathematical
convergence of q(t). Because the velocity profile within a blood
vessel tends towards zero at the blood vessel walls, the
contribution of the velocity rings to the calculation of volumetric
flowrate is less for the peripheral rings and more for the central
rings. Thus, as the calculation proceeds from the center to the
periphery of the blood vessel, the value of the calculated
volumetric flow rate will be seen to change more slowly as the
inner edge of the blood vessel is approached. This provides a means
of automatically identifying the diametric limits of the blood
vessel and improves the accuracy of the calculation. Accuracy is
further improved as the Doppler sampling volume is decreased.
[0072] Calculation of Time-Averaged Volume Flow Rate Q.
[0073] The time-averaged volume flow, calculated over several
instantaneous velocity profiles within a heart beat and over the
course of multiple heartbeats, yields an estimate of the net
forward volume flow through the blood vessel. This time-averaged
flow is described analytically as follows:
[0074] where
Q = 1 .tau. .intg. 0 t q ( t ) dt ##EQU00001## Q = time - averaged
volume flow rate , and ##EQU00001.2## .tau. = sampling period .
##EQU00001.3##
[0075] The analytical expression for volume flow rate Q, shown
above, can be discretized for the estimation of volume flow from
distinct digitized velocity profiles collected, for example, with a
pulsed-wave ultrasound velocity probe. Velocity profiles can be
measured at intervals of .DELTA.t, over a sampling period .tau..
The resulting estimate of average volume flow rate during the
sampling period .tau. then becomes:
.tau./.DELTA.t
Q=.DELTA./.tau..SIGMA.q(t).DELTA.t
n=0
[0076] For completeness the following is a combination of previous
expressions and is the formula for volume flow estimation by the
described method:
.tau./.DELTA.t
Q=.DELTA.t/.tau..SIGMA.(q.sub.0+.SIGMA.u.sub.n*pi*(d.sub.n.sup.2-d.sup.2-
.sub.n-1)/4).DELTA.t
n=0
[0077] The iterative calculation described above is preferably
performed by automated computer processing of pulsed wave Doppler
velocity data.
[0078] FIG. 10 shows sequential velocity profiles captured during a
sampling period in a canine blood vessel. The example data was
obtained by collecting velocity profiles in a canine pulmonary
blood vessel at a temporal sampling rate of approximately 7 Hz. The
Doppler probe system used was a MetFlow UVP Duo with TX-8
transducer, Lausanne, Switzerland. In particular, a transbronchial
catheter was advanced into an airway in the vicinity of the right
branch of the pulmonary artery in the dog. This artery is typically
6-8 mm in diameter in a dog. Velocity data was then detected using
the pulsed wave ultrasound probe.
[0079] It is noteworthy in FIG. 10 that the instantaneous velocity
profiles vary within a heartbeat, as would be expected as the blood
flow surges and then subsides and finally reverses within the
different sub-stages of the heartbeat. The measurements are
therefore preferably carried out over an extended time duration in
order to obtain a time averaged flowrate representative of the net
volume flowrate through the blood vessel. As discussed above,
suitable time durations range from 6-10 seconds, or longer.
[0080] FIG. 11 shows two time-averaged volume flowrate lines. The
lines represent time-averaged volume flowrates using different
diameter thresholds as referred to in Section [0070]. The dashed
line corresponds to an calculated maximum diameter of 8.9 mm, and
the solid line corresponds to a calculated maximum diameter was 7.4
mm. Q(t) was calculated, as described above, namely, by adding
component annular volume flowrates together. As shown, both lines
converge to a nearly constant value after approximately 10 cardiac
cycles (i.e. after approximately 6 seconds of data collection),
indicating that a diameter of 8.9 mm does not subtend any
additional flow and is therefore beyond the vessel wall; and that
7.4 mm is a correct representation of the vessel diameter. The data
shown in FIG. 11 is uncalibrated, so the steady-state volume "flow
rate is not expected to be physiologic. However, calibration is a
well known exercise to those having skill in the art.
[0081] FIG. 11, and in particular, the clear convergence of the two
lines, suggests that so long as the sampling range spans the vessel
and extends to the zero velocity regions along the edge of the
vessel (or beyond), the present invention provides an estimate of
the average flowrate regardless of the diameter of the vessel.
Thus, so long as the conditions described above are met, and the
iterative calculation for q(t) proceeds to a diameter greater than
the vessel of interest, an accurate volume flowrate can be
estimated.
[0082] Estimation of Cardiac Output.
[0083] Cardiac output may be estimated in accordance with the
present invention. The right and left main pulmonary arteries are
both positioned anatomically adjacent to the right and left main
bronchi. Thus, by probing both of these arteries and summing the
resulting blood volume flows, one will obtain an estimate of
cardiac output. One can also obtain an estimate of cardiac output
by probing one or the other of the right or left pulmonary arteries
and doubling the blood volume flow from that artery. This latter
method relies on the assumption that cardiac output blood volume
flow is distributed equally to the right and left pulmonary
arteries. After calibration of the system, it is expected that the
invention would accurately estimate cardiac output in human
subjects, with measurements in the physiological range of 1-10
liters per minute.
[0084] All patents, applications, and publications referenced above
are hereby incorporated by reference in their entirety.
* * * * *