U.S. patent application number 13/941587 was filed with the patent office on 2014-06-12 for cerebral perfusion monitor.
This patent application is currently assigned to Orsan Medical Technologies Ltd.. The applicant listed for this patent is Orsan Medical Technologies Ltd.. Invention is credited to Shlomi Ben-Ari, Ben Zion Poupko, Yosef Reichman.
Application Number | 20140163404 13/941587 |
Document ID | / |
Family ID | 39942982 |
Filed Date | 2014-06-12 |
United States Patent
Application |
20140163404 |
Kind Code |
A1 |
Reichman; Yosef ; et
al. |
June 12, 2014 |
Cerebral Perfusion Monitor
Abstract
A method of estimating cerebral blood flow by analyzing IPG and
PPG signals of the head, the method comprising: a) finding a
maximum slope or most negative slope or the IPG signal, within at
least a portion of the cardiac cycle; b) finding a maximum slope or
most negative slope of the PPG signal, within at least a portion of
the cardiac cycle; c) finding a ratio of the maximum or most
negative slope of the IPG signal to the maximum or most negative
slope of the PPG signal; and d) calculating a cerebral blood flow
indicator from the ratio.
Inventors: |
Reichman; Yosef; (Kfar-Saba,
IL) ; Poupko; Ben Zion; (Nes Ziona, IL) ;
Ben-Ari; Shlomi; (Binyamina, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Orsan Medical Technologies Ltd. |
Netanya |
|
IL |
|
|
Assignee: |
Orsan Medical Technologies
Ltd.
Netanya
IL
|
Family ID: |
39942982 |
Appl. No.: |
13/941587 |
Filed: |
July 15, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11921937 |
Dec 11, 2007 |
8512253 |
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PCT/IB2006/050174 |
Jan 17, 2006 |
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13941587 |
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PCT/IL2005/000631 |
Jun 15, 2005 |
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11921937 |
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PCT/IL2005/000632 |
Jun 15, 2005 |
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PCT/IL2005/000631 |
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10893570 |
Jul 15, 2004 |
7998080 |
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PCT/IL2005/000631 |
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10893570 |
Jul 15, 2004 |
7998080 |
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PCT/IL2005/000632 |
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PCT/IL03/00042 |
Jan 15, 2003 |
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10893570 |
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60348278 |
Jan 15, 2002 |
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Current U.S.
Class: |
600/506 |
Current CPC
Class: |
A61B 2562/164 20130101;
A61B 5/0295 20130101; A61B 5/04008 20130101; A61B 5/0265 20130101;
A61B 5/0535 20130101; A61B 5/6817 20130101; A61B 5/0261 20130101;
A61B 5/6814 20130101 |
Class at
Publication: |
600/506 |
International
Class: |
A61B 5/0295 20060101
A61B005/0295 |
Claims
1. A method of estimating cerebral blood flow by analyzing IPG and
PPG signals of the head, the method comprising: a) finding a
maximum slope or most negative slope or the IPG signal, within at
least a portion of the cardiac cycle; b) finding a maximum slope or
most negative slope of the PPG signal, within at least a portion of
the cardiac cycle; c) finding a ratio of the maximum or most
negative slope of the IPG signal to the maximum or most negative
slope of the PPG signal; and d) calculating a cerebral blood flow
indicator from the ratio.
2.-23. (canceled)
Description
RELATED APPLICATIONS
[0001] The present application claims priority from, and is a
continuation-in-part of two related PCT patent applications
PCT/IL2005/000631 and PCT/IL2005/000632, both filed Jun. 15, 2005.
Those PCT applications are both continuations-in-part of U.S.
patent application Ser. No. 10/893,570, filed Jul. 15, 2004, which
is a continuation-in-part of PCT patent application PCT/IL03/00042,
filed Jan. 15, 2003, which claims benefit under 35 USC 119(e) from
U.S. provisional patent application 60/348,278, filed Jan. 15,
2002. The disclosures of all of these applications are incorporated
herein by reference.
FIELD OF THE INVENTION
[0002] The field of the invention relates to measuring blood flow
in the head.
BACKGROUND OF THE INVENTION
[0003] There is a need to measure cerebral blood flow during
various medical events and procedures, because any disturbance to
the flow of blood to the brain may cause injury to the function of
the brain cells, and even death of brain cells if the disturbance
is prolonged. Maintaining blood flow to the brain is especially
important because brain cells are more vulnerable to a lack of
oxygen than other cells, and because brain cells usually cannot
regenerate following an injury.
[0004] A number of common situations may cause a decrease in the
general blood flow to the brain, including arrhythmia, myocardial
infarction, and traumatic hemorrhagic shock. A sudden increase in
blood flow to the brain may also cause severe damage, and is
especially likely to occur in newborn or premature babies, although
such an increase may also occur in other patients with certain
medical conditions, or during surgery. In all these cases, data
regarding the quantity of blood flow in the brain, and the changes
in flow rate, may be important in evaluating the risk of injury to
the brain tissue and the efficacy of treatment. The availability of
such data may enable the timely performance of various medical
procedures to increase, decrease, or stabilize the cerebral blood
flow, and prevent permanent damage to the brain.
[0005] In the absence of a simple means for direct and continuous
monitoring of cerebral blood flow, information about changes in
cerebral blood flow is inferred indirectly by monitoring clinical
parameters which can be easily measured, such as blood pressure.
But due to the different relation between blood pressure and
cerebral blood flow in different medical conditions, there may be
situations in which cerebral blood flow is inadequate even when
blood pressure appears to be adequate. Cerebral blood flow may also
be inferred indirectly by monitoring neurological function, but
since neurological dysfunction is often irreversible by the time it
is detected, it is more desirable to detect changes in cerebral
blood flow directly, while its effects on brain function are still
reversible.
[0006] Existing means for measuring cerebral blood flow are
complex, expensive, and in some cases invasive, which limits their
usefulness. Three methods that are presently used only in research
are 1) injecting radioactive xenon into the cervical carotid
arteries and observing the radiation it emits as it spreads
throughout the brain; 2) positron emission tomography, also based
on the injection of radioactive material; and 3) magnetic resonance
angiography, performed using a room-sized, expensive, magnetic
resonance imaging system, and requiring several minutes to give
results. These three methods can only be carried out in a hospital
or other center that has the specialized equipment available, and
even in a hospital setting it is not practical to monitor patients
continuously using these methods.
[0007] A fourth method, trans-cranial Doppler (TCD) uses
ultrasound, is not invasive and gives immediate results. However,
TCD fails to give a correct determination of blood flow in about
15% of patients, due to the difficulty of passing sound waves
through the cranium, and it requires great skill by professionals
who have undergone prolonged training and practice in performing
the test and deciphering the results. Another disadvantage of TCD
is that it measures only regional blood flow in the brain, and does
not measure global blood flow. Doppler ultrasound may also be used
to measure blood flow in the carotid arteries, providing an
estimate of blood flow to the head, but not specifically to the
brain, and not including blood flow to the head through the
vertebral arteries. Blood flow through the vertebral arteries is
difficult to measure by ultrasound because of their proximity to
the vertebrae.
[0008] Two additional techniques that are used, generally in
research, to measure blood flow in the head and in other parts of
the body are electric impedance plethysmography (IPG) and
photoplethysmography (PPG). U.S. Pat. No. 6,819,950, to Mills,
(disclosure of which is incorporated by reference) are describes
the use of PPG to detect carotid stenosis, among other conditions.
U.S. Pat. No. 5,694,939, to Cowings, (disclosure of which is
incorporated by reference) describes biofeedback techniques for
controlling blood pressure, which include the use of IPG in the
lower leg and PPG in the finger. U.S. Pat. No. 5,396,893, to Oberg
et al, (disclosure of which is incorporated by reference) states
that PPG is superior to IPG for monitoring patients' cardiac and
respiration rates. U.S. Pat. No. 6,832,113, to Belalcazar,
(disclosure of which is incorporated by reference) describes the
use of either IPG or PPG to measure blood flow, for purposes of
optimizing a cardiac pacemaker. U.S. Pat. No. 6,169,914, to Hovland
et al, (disclosure of which is incorporated by reference) describes
the use of various types of sensors, including IPG and PPG, for
monitoring female sexual arousal with a vaginal probe, and
describes using different types of sensors in combination.
[0009] U.S. Pat. No. 6,413,223, to Yang et al, (disclosure of which
is incorporated by reference) describes a probe, used on the
finger, which contains two PPG sensors and one IPG sensor. The
combined data from the three sensors, analyzed using a mathematical
model of arterial blood flow, provides a more accurate measurement
of blood flow than would be obtained by using IPG or PPG alone.
[0010] J. H. Seipel and J. E. Floam, in J. Clinical Pharmacology
15, 144-154 (1975) present the results of a clinical study of the
effects of a drug, betahistidine, on cerebral, cranial, scalp and
calf blood circulation. Rheoencephalography (REG), a form of IPG,
was used to measure the amplitude of cerebral blood flow.
[0011] The disclosures of all of the above mentioned patents and
publication are incorporated herein by reference.
SUMMARY OF THE INVENTION
[0012] An aspect of some embodiments of the invention relates to
determining cerebral blood flow from IPG data, using the data only
from selected cardiac cycles, and discarding the data from other
cardiac cycles, according to characteristics of the IPG data and/or
other data, for example EKG data. Optionally, the IPG data is
obtained from electrodes placed on the head or in ears, for example
as described in any of the above mentioned related patent
applications. Optionally, the cerebral blood flow is determined
from a combination of IPG data and PPG data, and characteristics of
the IPG data, the PPG data, other data, or any combination of them,
are used to select cardiac cycles from which the IPG and PPG data
is used. Optionally, the PPG data is obtained from PPG sensors
placed on the head or in the ears, for example as described in any
of the above mentioned related patent applications. Optionally,
these characteristics comprise the duration of the cardiac cycle,
and data is used for cardiac cycles that have similar duration,
while cardiac cycles with very different durations are discarded.
Additionally or alternatively, the characteristics comprise a
cross-correlation between the signal for each cardiac cycle and the
following (or preceding) cardiac cycle, for the IPG signal and/or
for the PPG signal. For example, data is used for a cardiac cycle
only if the cross-correlation exceeds a threshold, for the IPG
signal or for the PPG signal, or only if the cross-correlation
exceeds a threshold for both the IPG and PPG signals.
[0013] As aspect of some embodiments of the invention relates to
reducing breathing artifacts from IPG data and/or PPG data, before
using the IPG data, or a combination of the IPG and PPG data, to
measure cerebral blood flow. Breathing artifacts are reduced, for
example, by adjusting the data differently in each cardiac cycle,
such that the data at a particular phase in the cardiac cycle, or
an average of the data over a particular range of phases of the
cardiac cycle, always has a fixed value. Optionally, breathing
artifacts are substantially removed from the IPG data and/or from
the PPG data, for example the cerebral blood flow calculated from
the IPG and PPG data varies by less than 10% as a function of phase
of the breathing cycle, on average over many breathing cycles.
Optionally, the particular phase in the cardiac cycle is the
diastolic phase, as indicated, for example, by the peak of the
R-wave, or as indicated by a minimum in the IPG signal or the PPG
signal.
[0014] An aspect of some embodiments of the invention relates to
using a ratio of a slope, optionally a maximum slope of the IPG
signal to a slope, optionally a maximum slope of the PPG signal, as
a measure of cerebral blood flow. This slope is believed to be
strongly correlated with the blood inflow. Optionally, the maximum
slope used for both the IPG and PPG signals is the maximum slope of
the leading edge, following the diastolic phase. Alternatively, the
maximum slope used for one or both signals is the slope of maximum
absolute value at the trailing edge, preceding the diastolic phase.
Optionally, the maximum slope is normalized, for example by
dividing it by a measure of the amplitude of the signal for that
cardiac cycle. Optionally, the resulting measurement of cerebral
blood flow is then smoothed by using an average over time. For
example, a running average over time is used, with a fixed time
interval, for example a few seconds, or with a fixed number of
cardiac cycles. Optionally, the smoothing is done over a time
interval that varies with time, adapting to characteristics of the
signal.
[0015] There is thus provided, in accordance with an exemplary
embodiment of the invention, a method of estimating cerebral blood
flow by analyzing IPG and PPG signals of the head, the method
comprising: [0016] a) finding a maximum slope or most negative
slope or the IPG signal, within at least a portion of the cardiac
cycle; [0017] b) finding a maximum slope or most negative slope of
the PPG signal, within at least a portion of the cardiac cycle;
[0018] c) finding a ratio of the maximum or most negative slope of
the IPG signal to the maximum or most negative slope of the PPG
signal; and [0019] d) calculating a cerebral blood flow indicator
from the ratio.
[0020] Optionally, finding the maximum or most negative slope
comprises finding the maximum slope, for both the IPG and PPG
signals, and finding a ratio comprises finding a ratio of the
maximum slopes.
[0021] Optionally, the maximum slopes are maximums within a leading
portion of the cardiac cycle.
[0022] Alternatively, finding the maximum or most negative slope
comprises finding the most negative slope, for both the IPG and PPG
signals, and finding a ratio comprises finding a ratio of the most
negative slopes.
[0023] Optionally, the most negative slopes are most negative
within a trailing portion of the cardiac cycle.
[0024] In an embodiment of the invention, the maximum or most
negative slope of at least one of the signals is normalized to a
measure of the amplitude of said signal.
[0025] Optionally, the measure of the amplitude is the peak-to-peak
amplitude of said signal over the cardiac cycle.
[0026] Alternatively, the measure of the amplitude is an average
value of said signal over the cardiac cycle.
[0027] Optionally, the PPG signal comes from a PPG sensor on the
left side of the head.
[0028] Additionally or alternatively, the PPG signal comes from a
PPG sensor on the right side of the head.
[0029] Additionally or alternatively, the PPG signal is an average
of signals from a PPG sensor on the left side of the head and a PPG
sensor on the right side of the head.
[0030] There is further provided, in accordance with an exemplary
embodiment of the invention, a method of estimating time-varying
cerebral blood flow, comprising: [0031] a) obtaining a time-varying
IPG signal of the head; [0032] b) obtaining a time-varying PPG
signal of the head; [0033] c) using the IPG and PPG signals to
calculate a time-varying indicator for cerebral blood flow; and
[0034] d) performing data processing on one or more of the IPG
signal, the PPG signal, and the cerebral blood flow indicator, to
reduce noise or artifacts or both.
[0035] In an embodiment of the invention, performing data
processing comprises discarding data of the IPG signal, the PPG
signal, or both, for cardiac cycles which meet one or more criteria
for discarding.
[0036] Optionally, the criteria comprise having a duration outside
an expected range.
[0037] Optionally, the expected range has a maximum between 1.3 and
2 times an average duration of cardiac cycles.
[0038] Additionally or alternatively, the criteria comprise one or
both of the IPG signal and the PPG signal having a
cross-correlation below a threshold, between that cardiac cycle and
the following cardiac cycle.
[0039] Additionally or alternatively, the criteria comprise one or
both of the IPG signal and the PPG signal having a
cross-correlation below a threshold, between that cardiac cycle and
the preceding cardiac cycle.
[0040] Optionally, the threshold is between +0.5 and +0.8.
[0041] In an embodiment of the invention, performing data
processing comprises reducing breathing artifacts in the IPG
signal, the PPG signal, or both.
[0042] Optionally, calculating the cerebral blood flow indicator
comprises using the method according to an exemplary embodiment of
the invention.
[0043] In an embodiment of the invention, performing data
processing comprises smoothing the cerebral blood flow
indicator.
[0044] Optionally, smoothing comprises finding an average over a
time interval.
[0045] Optionally, smoothing comprises using a time scale that is
adjusted adaptively, depending on behavior of the cerebral blood
flow indicator as a function of time.
BRIEF DESCRIPTION OF THE DRAWINGS
[0046] Exemplary embodiments of the invention are described in the
following sections with reference to the drawings. The drawings are
not necessarily to scale and the same reference numbers are
generally used for the same or related features that are shown on
different drawings.
[0047] FIG. 1 is a flowchart of a method for finding cerebral blood
flow, according to an exemplary embodiment of the invention;
[0048] FIGS. 2A-2D schematically show graphs of IPG and PPG
signals, with breathing artifacts and with the breathing artifacts
removed, according to an exemplary embodiment of the invention;
[0049] FIG. 3 schematically shows a graph of IPG and PPG signals,
during good and bad cardiac cycles, according to an exemplary
embodiment of the invention;
[0050] FIG. 4 schematically shows a graph of a calculated cerebral
blood flow indicator as a function time during an endarterectomy
procedure, according to an exemplary embodiment of the
invention;
[0051] FIG. 5 schematically shows a graph of the cerebral blood
flow indicator shown in FIG. 4, showing the effect of including all
of the cardiac cycles, and including only the good cardiac cycles,
according to an exemplary embodiment of the invention;
[0052] FIG. 6 schematically shows a graph of the cerebral blood
flow indicator shown in FIG. 4, which was smoothed over time,
together with the values of the indicator before smoothing,
according to an exemplary embodiment of the invention;
[0053] FIG. 7 schematically shows a graph of a calculated cerebral
blood flow indicator of a subject as a function of time, according
to an exemplary embodiment of the invention, during a test in which
the cerebral blood flow was increased by having the subject breath
air with an increased level of carbon dioxide; and
[0054] FIG. 8 schematically shows a graph of a calculated cerebral
blood flow indicator for the left and right hemispheres of a
subject's brain as a function of time, according to an exemplary
embodiment of the invention, during a test in which the subject
performed a cognitive task which increased the left hemisphere
blood flow.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0055] FIG. 1 shows a flowchart 100, outlining a method for finding
cerebral blood flow (CBF) according to an exemplary embodiment of
the invention. The different steps in flowchart 100 will be
described with reference to graphs of data, shown in FIGS. 2, 3,
and 4.
[0056] At 102, raw IPG and PPG data of the head is acquired. The
data is acquired, for example, using any of the methods described
in any of the above mentioned related patent applications or the
patents, and publications as referenced in the Background, or any
other methods known in the art for acquiring IPG and PPG data of
the head. For example, combined sensors, incorporating both
electrodes for IPG and optical sensors for PPG, are used, or
separate sensors are used. Optionally, the IPG electrodes are
designed to be of a size and shape, and are positioned on the head,
so as to obtain IPG data that is relatively more sensitive to the
impedance of the interior of the skull, and relatively less
sensitive to the impedance of the scalp, as described in the above
mentioned patent applications. Examples of raw IPG and PPG signals
as a function of time are shown respectively in plots 202 and 204
of FIGS. 2A and 2B.
[0057] Optionally, there is more than one PPG sensor, for example,
there are two PPG sensors, one on each side of the head.
Optionally, the two PPG sensors are located respectively on the
left and right sides of the forehead. In any of the methods
described herein for using the PPG signal, either the PPG signal
from the left side of the head or the PPG signal from the right
side of the head may be used, or an average of the two PPG signals
may be used, possibly a weighted average.
[0058] At 104, the raw IPG and/or PPG signals are optionally
conditioned to reduce breathing artifacts. This is done, for
example, by adjusting the signals so that the minimum value for
each cardiac cycle has a constant value, set at zero in FIGS. 2C
and 2D. Methods of defining what constitutes a single cardiac cycle
are described below, in connection with 106. The resulting
conditioned IPG signal, shown in plot 206, and conditioned PPG
signal, shown in plot 208, are nearly free of breathing artifacts.
There is no apparent correlation of the IPG signals and PPG signals
with the breathing cycle visible to a casual viewer of plots 206
and 208, and any remaining correlation of the IPG signal and/or the
PPG signal to the breathing cycle optionally results in less than a
10% effect on the calculated cerebral blood flow. Optionally, the
values between minima are reduced by the average value or an
interpolated value of the adjacent minima.
[0059] Optionally, at 106, "good" cardiac cycles are selected, and
data from other cardiac cycles is discarded. Optionally, one or
more of three criteria are used for discarding data from some
cardiac cycles. The first criterion concerns how much the duration
of the cardiac cycle differs from an average duration. The second
and third criteria concern how much the form of the signal for a
given cardiac cycle differs from the form of the signal for the
following (or preceding) cardiac cycle, for the IPG signal and the
PPG signal respectively. Data from cardiac cycles which satisfy one
or more of these criteria is likely to have a high noise level
which distorts the signals, or may correspond to an irregular
heartbeat which does not provide a typical value for cerebral blood
flow. The inventors have found that discarding data for cardiac
cycles which satisfy any one of these three criteria is
particularly useful for determining an accurate measure of cerebral
blood flow. Optionally, data is discarded only if the cardiac cycle
satisfies two of these criteria, or all three criteria. Optionally,
only one of these three criteria is used as a criterion to discard
data. Optionally, only two of the criteria are used, and the data
is discarded if either of the two criteria is satisfied.
Optionally, all three criteria are used, and the data is discarded
if any of the criteria are satisfied. Other criteria for
determining if the data for a particular cardiac cycle should be
discarded will occur to a person of skill in the art.
[0060] The duration of the cardiac cycle is determined, for
example, using EKG data, and defined as the time from the peak of
one R-wave to the peak of the next R-wave. To be considered as the
peak of an R-wave, the peak optionally must meet certain criteria.
For example, the peak falls between 0.3 seconds and 1.5 seconds of
the peak of the previous R-wave. If there is more than one local
peak within this time interval, the peak of the R-wave is
optionally found by finding the peak which most resembles the
expected amplitude and time interval for the peak of an R-wave. The
expected amplitude and time interval are based, for example, on the
amplitude and time interval for the previous peak of an R-wave, or
on a running average of past values. Optionally, instead of or in
addition to using the peak of the R-wave to define the duration of
the cardiac cycles, IPG data and/or PPG data is used. For example,
the duration of a cardiac cycle is defined as the time from one
local minimum (or maximum) to the next local minimum (or maximum)
in the IPG and/or the PPG signal, or as the time from one local
maximum (or minimum) in slope of the signal to the next local
maximum (or minimum) in slope. Optionally, the local minimum or
maximum in the IPG or PPG signal, or in the slope of the IPG or PPG
signal, must meet certain criteria, for example criteria similar or
identical to the criteria described above for using the peak of the
R-wave. Optionally, data is discarded for those cardiac cycles that
have a duration outside an expected range. Optionally, the maximum
of the expected range is between 1.3 and 2 times an average
duration of a cardiac cycle. For example, the maximum is 1.65 times
the average duration. Alternatively, the maximum of the expected
range is less than 1.3 times the average duration. Optionally, the
minimum of the expected range is less than 0.7 times the average
duration. Alternatively, the minimum of the expected range is more
than 0.7 times the average duration. Optionally, there is no
explicit minimum to the range, although there may be a minimum
duration for any cardiac cycle, due to the way that cardiac cycles
are defined, as described above.
[0061] The "average duration of a cardiac cycle" described above is
optionally the median or the mode of the durations of the cardiac
cycles. A potential advantage of using the median or the mode,
rather than the mean, is that the median and the mode are
relatively insensitive to the values of outliers that may represent
noise in the data rather than real durations of cardiac cycles.
Alternatively, the "average duration of a cardiac cycle" is the
mean of the durations of cardiac cycles. Optionally, the "average
duration of a cardiac cycle" is a running average, for example over
several cardiac cycles, or over several tens of cardiac cycles.
Using a running average for the average duration of a cardiac cycle
has the potential advantage of adjusting the average duration to
real changes in the patient's pulse rate, due to physiological
changes over time. Optionally, a fixed value is used in place of
the "average duration of a cardiac cycle," optionally adjusted to
the patient, or the fixed value is based on a pulse rate determined
for that patient.
[0062] How much the form of the signal (either the IPG or PPG
signal) for a given cardiac cycle differs from the signal for the
following cardiac cycle, is determined, for example, by the
cross-correlation between the signals for the two cardiac cycles.
Optionally, if the cross-correlation is less than some threshold,
for one or both of the IPG and PPG signals, then the data for that
cardiac cycle is discarded. Optionally, the threshold is between
+0.5 and +0.8, for example the threshold is +0.7. Optionally,
instead of using the cross-correlation between a cardiac cycle and
the following cardiac cycle for the criterion, the criterion is
based on the cross-correlation between the cardiac cycle and the
previous cardiac cycle. Alternatively, the data is discarded only
if either of these two cross-correlations is less than the
threshold, or only if both cross-correlations are less than the
threshold. Optionally, the data is discarded only if the
cross-correlation (whichever one is used) is below the threshold
for both the IPG and PPG signals. Alternatively, the data is
discarded only if the cross-correlation is below the threshold for
the IPG signal, or only if the cross-correlation is below the
threshold for the PPG signal.
[0063] FIG. 3 shows a plot 300 of conditioned IPG data 302 (solid
curve) and conditioned PPG data 304 (dashed curve). For the first
two cardiac cycles, in time intervals 306 and 308, the
cross-correlation between that cardiac cycle and the next is
relatively low for the IPG data, apparently because of noise in the
IPG data, and the data for these cardiac cycles is discarded. For
the remaining cardiac cycles, the cross-correlation between that
cardiac cycle and the next is relatively high, for both the IPG and
the PPG signals, and the data for these cardiac cycles is not
discarded.
[0064] At 108, a CBF indicator is calculated from the IPG and/or
PPG data for the cardiac cycles for which the data has been kept.
In an exemplary embodiment of the invention, the CBF indicator is
found, for each such cardiac cycle, by taking the ratio of the
maximum slope of the IPG signal to the maximum slope of the PPG
signal. Optionally, the maximum slopes are not necessarily maximums
over the whole cardiac cycle, but are maximums over a leading edge
portion of the cardiac cycle, following the diastolic phase. It
should be understood that the magnitudes of both the IPG and PPG
signals, and hence the maximum slopes of both signals, in general
may be sensitive to various factors. These factors include the
exact position of the electrodes and PPG sensors on the patient's
head, how good the contact is with the skin, and the thickness of
the patient's skin and of the fatty layer beneath the patient's
skin at the location of the electrodes and elsewhere on the
patient's head. The ratio of the maximum slopes of the IPG and PPG
signals may not provide an absolute measure of cerebral blood flow,
but may provide only a relative measure of cerebral blood flow.
Optionally, the measure of cerebral blood flow is calibrated by
observing its value at a time when the patient is known to have
adequate cerebral blood flow, for example before surgery, at a time
when the patient is conscious and his mental state can be assessed
by asking him questions. Optionally, the electrodes and PPG sensors
are not removed or repositioned once the measure of cerebral blood
flow has been calibrated, until surgery has been completed, for
example.
[0065] Because the arteries in the brain are generally greater in
diameter than the arteries of the skin of the face and the scalp,
the blood volume in the brain generally increases sooner and faster
at the beginning of the systolic phase, than the blood volume in
the skin does. Because the IPG signal is sensitive both to the
blood volume in the brain and the blood volume in the skin, while
the PPG signal is sensitive only to the blood volume in the skin,
the IPG signal generally rises sooner and faster, at the beginning
of the systolic phase, than the PPG signal. The maximum slope of
each signal is a measure of how fast this rise occurs, and how high
the rise goes. The maximum slope of the IPG signal is a measure of
a weighted sum of the blood flow in the brain and the blood flow in
the skin, while the maximum slope of the PPG signal is a measure of
the blood flow in the skin alone. The maximum slopes of the IPG and
PPG signals may be better measures of blood flow in these regions
than the peak-to-peak amplitude of the IPG and PPG signals, which
measure changes in blood volume. The change in blood volume depends
on the difference between blood flow into and out of a region.
However, the peak-to-peak amplitudes of the IPG and PPG signals may
also be useful for measuring cerebral blood flow.
[0066] Another useful measure of blood flow, for either the IPG
signal or the PPG signal or both, is the maximum slope of the
signal normalized to a measure of the amplitude of the signal. For
example, the maximum slope is normalized by dividing by the
peak-to-peak amplitude of the signal for that cardiac cycle.
Alternatively, the maximum slope is normalized by dividing by a
difference between an average value of the signal, possibly a
weighted average value, and the minimum value of the signal, for
that cardiac cycle. Optionally the weighted average value includes
both positive and negative weights, for example the weighted
average value is a Fourier component of the signal at the cardiac
cycle frequency. Optionally, the normalization is to the area of
the signal for example between successive minima.
[0067] The inventors have found that the ratio of maximum slope of
the IPG signal to maximum slope of the PPG signal (either
normalizing the maximum slopes or not) is often well correlated
with blood flow rate in the brain in certain circumstances, as
determined independently by other means, for example TCD. For
example, in certain circumstances, the brain increases cerebral
blood flow by constricting peripheral arteries which affect blood
flow to the scalp and to the skin of the face. In these cases, an
increase in cerebral blood flow correlates with a decrease in blood
flow in the skin, and the ratio of maximum slope of IPG signal to
maximum slope of PPG signal may be well correlated with cerebral
blood flow.
[0068] In circumstances where cerebral blood flow is reduced by
blocking or bleeding of an artery on one side of the head, the
peripheral blood flow on the other side of the head may remain
relatively constant. In these cases, particularly if the PPG signal
is measured on the other side of the head from the affected artery,
the ratio of the maximum slope of the IPG signal to the maximum
slope of the PPG signal may also be well correlated with cerebral
blood flow. Even if the PPG signal is taken on the same side of the
head as the affected artery, the ratio of maximum slopes may be
reasonably well correlated with cerebral blood flow, perhaps
because collateral arteries may redistribute blood from one side of
the head to the other.
[0069] In other circumstances, different measures of cerebral blood
flow may be more useful. For example, if total blood flow to the
head is reduced because of a decrease in blood pressure, then the
brain may compensate by constricting peripheral arteries, reducing
blood flow in the skin more than in the brain. In this case, the
maximum slope of the IPG signal alone, or a weighted difference in
maximum slopes between the IPG and PPG signals, may be a better
measure of cerebral blood flow than the ratio of the maximum
slopes.
[0070] In some embodiments of the invention, a different formula is
used for finding the CBF indicator. For example, instead of using
ratios of the maximum slopes of the IPG and PPG signals, the ratio
of the minimum (most negative) slopes is used instead, with the
slopes either normalized to a measure of the amplitudes or not.
Optionally, the most negative slopes are not necessarily the most
negative over the whole cardiac cycle, but only over a trailing
edge portion of the cardiac cycle, following the systolic phase.
The fall in blood volume after the systolic phase, like the rise in
blood volume after the diastolic phase, may be faster for the brain
than for the skin. The ratio of minimum slopes of the IPG and PPG
signals may be related to cerebral blood flow in a similar way to
the ratio of maximum slopes. Alternatively, when taking the ratio
of slopes, the maximum slope is used for one of the signals and the
minimum slope (or its absolute value) is used for the other
signal.
[0071] Alternatively or additionally, the CBF indicator is found by
subtracting a weighted PPG signal from the IPG signal, and then
taking the maximum slope of the difference signal. Optionally, the
weighting factor is determined by requiring a slope of the trailing
edge of the weighted PPG signal, for example an average slope of
the trailing edge, or a steepest slope of the trailing edge, to be
equal to the corresponding slope of the IPG signal. This choice of
weighting factor may be appropriate if the trailing edge of the IPG
signal is dominated by blood flow in the skin. The resulting CBF
indicator has the potential advantage that it may better indicate
changes in cerebral blood flow caused by a decrease in blood
pressure, which decreases blood flow in both the brain and the
skin. On the other hand, a CBF indicator based on the ratios of the
slopes of two signals may be less sensitive to noise in the signals
than a CBF indicator based on the slope of a difference between two
signals.
[0072] Optionally, the CBF indicator is based only on the IPG
signal, or only on the PPG signal. For example, the CBF indicator
is the peak-to-peak amplitude of one of the signals in each cardiac
cycle, or the maximum or minimum slope of one of the signals, or
the maximum or minimum slope normalized to an amplitude of the
signal, in each cardiac cycle.
[0073] In 110, the CBF indicator signal is averaged over time,
using any known algorithm for temporal smoothing. Optionally, the
averaging is done over a time scale of several seconds, for example
over 5, 10, or 20 seconds, or over a plurality of cardiac cycles,
for example over 5, 10, or 20 cardiac cycles. Optionally, the time
scale for the smoothing varies adaptively, depending on the data
being smoothed. For example, the smoothing comprises averaging the
data over a time interval which is adjusted upward if a linear
extrapolation makes a good prediction about where the next data
point will be, and is adjusted downward if a linear extrapolation
makes a poor prediction about where the next data point will
be.
[0074] Optionally, instead of, in addition to, averaging the CBF
indicator over a plurality of cardiac cycles, the IPG signals for
each of a plurality of cardiac cycles are superimposed and averaged
together, and the same is optionally done for the PPG signal,
before finding the CBF indicator in 108, using any of the methods
described above.
[0075] FIG. 4 shows a graph 400, with a plot of a smoothed CBF
indicator signal 402 as a function of time. The CBF indicator was
calculated by taking the ratio of the normalized maximum slope of
the IPG signal to the normalized maximum slope of the PPG signal,
with the normalization done using the peak-to-peak amplitude of
each signal. The smoothing of the CBF indicator was done by
averaging over an adaptively varying time interval, as described
above. The IPG and PPG signals were measured on a patient
undergoing an endarterectomy, in which the common, internal, and
external carotid arteries on one side of the neck were clamped
between time 406 and time 408, while the arteries were cleared of
plaque. The PPG data used was taken from the side of the head
opposite to the clamped arteries. The CBF indicator signal 402
decreases at time 406, primarily due to a decrease in the IPG
signal, when the arteries are clamped and blood flow to that side
of the head, and to the brain as a whole, is reduced. At time 408,
when the clamped arteries are released, the CBF indicator signal
402 increases, primarily due to an increase in the IPG signal. The
CBF indicator signal is higher after time 408 than it was before
the arteries were clamped, because the arteries cleared of plaque
allow greater cerebral blood flow than before.
[0076] It should be noted that this method of calculating the CBF
indicator has been found by the inventors to generally give the
best results for cerebral blood flow during an endarterectomy, of
the methods that have been tested. However some other methods of
calculating the CBF indicator, including using the PPG signal from
the same side of the head as the clamped arteries, have also been
found to give a fairly good indication of cerebral blood flow
during endarterectomy.
[0077] FIG. 5 shows a graph 500, illustrating the effect on the CBF
indicator of discarding bad cardiac cycles. The CBF indicator
signals shown in graph 500 were calculated from the same data used
in FIG. 4. CBF indicator signal 402, shown as a solid line, was
calculated using only "good" cardiac cycles, and is the same as
signal 402 shown in FIG. 4. Good cardiac cycles were defined as
those for which the duration of the cardiac cycle was less than
1.65 times the median duration of all cardiac cycles, and for which
both the IPG and PPG signals had a cross-correlation of at least
+0.7 between that cardiac cycle and the following cardiac cycle.
CBF indicator signal 502, shown as a dashed line, was calculated in
the same way, but including signal data from all cardiac cycles.
Although signal 502 shows the same general trend as signal 402,
decreasing while the arteries are clamped and returning to an even
higher level after the arteries are released, signal 502 shows
considerably more noise than signal 402.
[0078] FIG. 6 shows a graph 600, illustrating the effect of
smoothing on the CBF indicator. Smoothed CBF indicator 402 plotted
in graph 600 is the same as signal 402 plotted in FIGS. 4 and 5. A
large number of small stars 602 show the values of the CBF
indicator for individual cardiac cycles, which show a much higher
level of noise than smoothed signal 402.
[0079] FIGS. 7 and 8 show the results of two other tests that were
performed by the inventors to verify the usefulness of the CBF
indicator signal, using healthy volunteers. In these tests, CBF
indicators 702 (in FIG. 7) and 802 and 806 (in FIG. 8) were defined
as the ratio of the maximum slope of the IPG signal to the maximum
slope of one of the PPG signals, but the maximum slopes were not
normalized to the amplitudes of the respective signals. This method
of calculating the CBF indicator generally gave better results in
these two tests, than using normalized maximum slopes did. The
smoothing method, and the definition of "good" cardiac cycles, were
the same as for CBF indicator 402 in FIGS. 4-6.
[0080] In the test used to generate the data plotted in graph 700
in FIG. 7, the subject breathed normal air until time 708. Between
time 708 and time 710, the subject breathed from a closed bag,
resulting in an increased level of carbon dioxide, a procedure
which is known to provoke an increase in cerebral blood flow. After
time 710, the subject returned to breathing normal air. The
measured level of carbon dioxide in the gas that the subject
exhaled, relative to a typical normal exhaled carbon dioxide
partial pressure of 40 mm Hg, is plotted in graph 700 as signal
704. As expected, CBF indicator 702 rises when the level of carbon
dioxide rises, and falls again when the level of carbon dioxide
falls. The change in CBF indicator 702 is due largely to changes in
the PPG signal, which decreases when the level of carbon dioxide
increases, because the brain constricts peripheral arteries of the
head, in order to assure a continued adequate supply of oxygen to
the brain. A smoothed TCD signal 704, a standard indicator for
cerebral blood flow, shows a similar rise when the level of carbon
dioxide rises.
[0081] FIG. 8 illustrates the effect of cognitive activity on
cerebral blood flow. CBF indicator 802 was calculated using the PPG
signal from the left side of the head. CBF indicator 802 should
indicate specifically the blood flow in the left side of the brain,
since the brain is known to constrict or relax the peripheral
arteries separately on either the left or the right side of the
head, in order to regulate the blood flow on the corresponding
sides of the brain. The subject was presented with nine
multiplication problems, and asked to solve them in his head, at
the times indicated by arrows 804. Mental arithmetic is known to be
an activity primarily of the left side of the brain, and during the
time the subject was solving the problems, CBF indicator 802 showed
an increase in left cerebral blood flow, with about a two minute
delay. By contrast, CBF indicator 806, which was calculated using
the PPG signal from the right side of the head, shows no such
increase, indicating that there was no increase in right cerebral
blood flow during this period. CBF indicator 806 may even show a
slight decrease during this period. The changes in both CBF
indicators are due primarily to changes in the PPG signal.
[0082] The invention has been described in the context of the best
mode for carrying it out. It should be understood that not all
features shown in the drawing or described in the associated text
may be present in an actual device, in accordance with some
embodiments of the invention. Furthermore, variations on the method
and apparatus shown are included within the scope of the invention,
which is limited only by the claims. Also, features of one
embodiment may be provided in conjunction with features of a
different embodiment of the invention. As used herein, the terms
"have", "include" and "comprise" or their conjugates mean
"including but not limited to." As used herein, the "slope" of a
signal can mean either the unnormalized slope or the normalized
slope, for example the slope normalized to a measure of the
amplitude of the signal.
* * * * *