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Claims  |
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What is claimed is:
1. An apparatus for measuring blood flow in a vascular bed, the apparatus
comprising:
means for illuminating a region of tissue having a vascular bed with
coherent light;
means responsive to light backscattered from the region of tissue for
producing a broadened spectrum signal output;
circuit means coupled to said means for producing a broadened spectrum
signal output and responsive to its broadened spectrum signal output for
producing a signal representative of the blood flow in the vascular bed;
means for collecting backscattered light from the region of tissue;
wherein said means responsive to backscattered light comprise
photo-detector means responsive to the collected light for developing a
broadened spectrum of low frequency signals, said photo-detector means
producing a means current and having a substantially constant shot noise
output S;
wherein said circuit means comprise means coupled to said photo-detector
means and responsive to its output for developing an output signal I
representative of the mean current thereof, weighted detector means
coupled to said photo-detector and responsive to the broadened spectrum of
low frequency signals for developing an output signal R; and calculating
circuit means coupled to said weighted detector means and to said means
for developing an output signal I and responsive to outputs thereof for
producing an output signal F representative of the blood flow in the
vascular bed.
2. An apparatus according to claim 1, wherein said calculating circuit
comprises circuit means for producing an output signal F equal to
.sqroot.R.sup.2 - SI as a representation of blood flow parameter in the
vascular bed.
3. An apparatus according to claim 1, wherein said calculating circuit
comprises circuit means for producing an output signal F.sub.norm equal to
##EQU18##
as a representation of blood flow parameter in the vascular bed.
4. An apparatus according to claim 1, wherein said means for illuminating a
region of tissue comprises a laser.
5. An apparatus according to claim 4, wherein said laser is a He-Ne laser.
6. An apparatus according to claim 4, wherein said laser is a laser which
produces coherent light having a wave length of substantially 632.8 nm.
7. An apparatus according to claim 4, wherein said laser is a laser which
produces light having a wave length of substantially 805 nm.
8. An apparatus according to claim 1, wherein said photo-detector means
comprises a photomultiplier tube.
9. An apparatus according to claim 1, wherein said means for developing an
output signal I comprises amplifier means coupled to said photo-detector
means.
10. An apparatus according to claim 9, wherein said amplifier means
comprises a linear amplifier having an adjustable gain.
11. An apparatus according to claim 1, wherein said weighted detector means
is a root-mean-square detector.
12. An apparatus for measuring blood flow in a vascular bed, the apparatus
comprising:
means for illuminating a region of tissue having a vascular bed with
coherent light;
means responsive to light backscattered from the region of tissue for
producing a broadened spectrum signal output;
circuit means coupled to said means for producing a broadened spectrum
signal output and responsive to its broadened spectrum signal output for
producing a signal representative of the blood flow in the vascular bed;
and
means for collecting backscattered light from the region of tissue;
wherein said means responsive to backscattered light comprise
photo-detector means responsive to the collected light for developing a
broadened spectrum of low frequency signals, said photo-detector means
producing a mean current and having a substantially constant shot noise
output S;
wherein said circuit means comprise means coupled to said photo-detector
means and responsive to its output for developing an output signal I
representative of the mean current thereof, weighted detector means
coupled to said photodetector and responsive to the broadened spectrum of
low frequency signals for developing an output signal R; including
calculating circuit means coupled to said weighted detector means and to
said means for developing an output signal I and responsive to outputs
thereof for producing an output signal F representative of the blood flow
in the vascular bed, and
a differentiator means and a low pass filter connected between said
photo-detector means and said weighted detector means.
13. An apparatus according to claim 12, wherein said low pass filter is
connected between said photo-detector means and said differentiator means,
said differentiator means having its output coupled to said weighted
detector means for differentiating signals received from said low pass
filter means with respect to time and supplying these differentiated
signals to said weighted detector means.
14. An apparatus according to claim 13, wherein said low pass filter is an
adjustable filter for passing frequencies up to about 20 KHz.
15. A method of measuring the blood flow in a vascular bed, the method
comprising:
illuminating a region of tissue having a vasuclar bed with coherent light;
collecting at least some of the scattered light from the region;
detecting the collected light to determine its broadened spectrum; and
determining the blood flow in the vascular bed from said broadened
spectrum;
wherein said detecting step comprises non-linearly detecting the
backscattered light in a photo-detector to produce a broadened spectrum of
low frequency signals and a mean current signal I; and wherein the
determining step comprises producing a weighted output signal R from the
broadened spectrum of low frequency signals, determining the shot noise
constant S of the photo-detector, and producing a signal representation F,
from the shot noise constant, the weighted output signal R and the mean
current signal I.
16. A method according to claim 15, wherein the illuminating step comprises
illuminating a region tissue having a microvascular bed, the collecting
step comprises collecting at least some of the scattered light from the
microvascular bed, and the determining step comprises determining the flow
of red blood cells in the microvascular bed from said broadened spectrum.
17. A method according to claim 15, wherein the producing step comprises
producing an output F equal to .sqroot.R.sup.2 - SI as a representation of
blood flow parameter in the vascular bed.
18. A method according to claim 15, wherein the producing step comprises
producing a normalized output F.sub.norm equal to
##EQU19##
as a representation of blood flow parameter in the vascular bed.
19. A method according to claim 15, wherein said illuminating step
comprises illuminating a region of the tissue with coherent light having a
wave length of substantially 632.8 nm.
20. A method according to claim 15, wherein said illuminating step
comprises illuminating a region of the tissue with coherent light having a
wave length of substantially 805 nm.
21. A method according to claim 15, wherein the step of detecting the
broadened spectrum of low frequency signals comprises detecting the
broadened spectrum of low frequency signals to produce a root-mean-square
output signal R.
22. A method according to claim 15, including filtering the broadened
spectrum of low frequency signals to pass only signals below a given
frequency prior to detecting the broadened spectrum of low frequency
signals.
23. A method of measuring the blood flow in a vascular bed, the method
comprising:
illuminating a region of tissue having a vascular bed with coherent light;
collecting at least some of the scattered light from the region;
detecting the collected light to determine its broadened spectrum;
determining the blood flow in the vascular bed from said broadened
spectrum;
wherein said detecting step comprises non-linearly detecting the
backscattered light in a photo-detector to produce a broadened spectrum of
low frequency signals and a mean current signal I; and wherein the
determining step comprises producing a weighted output signal R from the
broadened spectrum of low frequency signals, determining the shot noise
constant S of the photo-detector, and producing a signal representation F,
from the shot noise constant, the weighted output signal R and the mean
current signal I;
filtering the broadened spectrum of low frequency signals to pass only
signals below a given frequency prior to detecting the broadened spectrum
of low frequency signals; and
differentiating the filtered low frequency signals with respect to time
prior to detecting the broadened spectrum of low frequency signals.
24. An apparatus for measuring the flow of flowing material, the apparatus
comprising:
means for illuminating at least a portion of the flowing material with
coherent light;
means for collecting backscattered light from the material;
photo-detector means responsive to the collected light for developing a
broadened spectrum of low frequency signals, said photo-detector means
producing a mean current and having a substantially constant shot noise
output S;
means coupled to said photo-detector means and responsive to its output for
developing an output signal I representative of the mean current thereof;
weighted detector means coupled to said photo-detector and responsive to
the broadened spectrum of low frequency signals for developing an output
signal R; and
calculating circuit means coupled to said weighted detector means and to
said means for developing an output signal I and responsive to outputs
thereof for producing an output signal F representative of the flow.
25. An apparatus according to claim 24, wherein said calculating circuit
comprises circuit means for producing an output signal F equal to
.sqroot.R.sup.2 - SI as a representation of flow parameter.
26. An apparatus according to claim 24, wherein said calculating circuit
comprises circuit means for producing an output signal F.sub.norm equal to
##EQU20##
as a representation of flow parameter.
27. An apparatus according to claim 24, wherein said photo-detector means
comprises a photomultiplier tube.
28. An apparatus according to claim 24, wherein said means for developing
an output signal I comprises amplifier means coupled to said
photo-detector means.
29. An apparatus according to claim 28, wherein said amplifier means
comprises a linear amplifier having an adjustable gain.
30. An apparatus according to claim 24, wherein said weighted detector
means is a root-mean-square detector.
31. An apparatus for measuring the flow of flowing material, the apparatus
comprising:
means for illuminating at least a portion of the flowing material with
coherent light;
means for collecting backscattered light from the material;
photo-detector means responsive to the collected light for developing a
broadened spectrum of low frequency signals, said photo-detector means
producing a mean current and having a substantially constant shot noise
output S;
means coupled to said photo-detector means and responsive to its output for
developing an output signal I representative of the mean current thereof;
weighted detector means coupled to said photodetector and responsive to the
broadened spectrum of low frequency signals for developing an output
signal R;
calculating circuit means coupled to said weighted detector means and to
said means for developing an output signal I and responsive to outputs
thereof for producing an output signal F representative of the flow; and
a differentiator means and a low pass filter connected between said
photo-detector means and said weighted detector means.
32. An apparatus according to claim 31, wherein said low pass filter is
connected between said photo-detector means and said differentiator means,
said differentiator means having its output coupled to said weighted
detector means for differentiating signals received from said low pass
filter means with respect to time and supplying these differentiated
signals to said weighted detector means.
33. An apparatus according to claim 32, wherein said low pass filter is an
adjustable filter for passing frequencies up to about 20 KHz.
34. A method of measuring the flow parameter of flowing material, the
method comprising:
illuminating at least a portion of the flowing material with coherent
light;
collecting at least some of the light scattered from the material;
non-linearly detecting the collected light in a photo-detector to produce a
broadened spectrum of low frequency signals and a mean current signal I;
detecting the broadened spectrum of low frequency signals to produce a
weighted output signal R;
determining the shot noise constant S of the photodetector; and
producing a signal representation F, from the shot noise constant, the
weighted output signal R and the mean current signal I.
35. A method according to claim 34, wherein the producing step comprises
producing an output F equal to .sqroot.R.sup.2 - SI as a representation of
flow parameter.
36. A method according to claim 34, wherein the producing step comprises
producing a normalized output F.sub.norm equal to
##EQU21##
as a representation of flow parameter.
37. A method according to claim 36, wherein the step of detecting the
broadened spectrum of low frequency signals comprises detecting the
broadened spectrum of low frequency signals to produce a root-mean-square
output signal R.
38. A method according to claim 34, including filtering the broadened
spectrum of low frequency signals to pass only signals below a given
frequency prior to detecting the broadened spectrum of low frequency
signals.
39. A method of measuring the flow parameter of flowing material, the
method comprising:
illuminating at least a portion of the flowing material with coherent
light;
collecting at least some of the light scattered from the material;
non-linearly detecting the collected light in a photo-detector to produce a
broadened spectrum of low frequency signals and a mean current signal I;
detecting the broadened spectrum of low frequency signals to produce a
weighted output signal R;
determining the shot noise constant S of the photo-detector;
producing a signal representation F, from the shot noise constant, the
weighted output signal R and the mean current signal I;
wherein the step of detecting the broadened spectrum of low frequency
signals comprises detecting the broadened spectrum of low frequency
signals to produce a root-mean-square output signal R;
filtering the broadened spectrum of low frequency signals to pass only
signals below a given frequency prior to detecting the broadened spectrum
of low frequency singals, and
differentiating the filtered low frequency signals with respect to time
prior to detecting the broadened spectrum of low frequency signals. |
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Claims |
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Description |
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BACKGROUND OF THE INVENTION
This invention relates to a method of an apparatus for measuring the flow
of red blood cells flowing in a microvascular bed. The present invention
relates, more particularly, to a method of an apparatus for measuring the
flow of red blood cells flowing in a microvascular bed, using the Doppler
scattering of coherent light. The invention can be practiced in connection
with the measuring of the blood flow parameters of kidney tissues, brain
tissues, liver tissues, tissues of other organs, and local cutaneous
tissues, as well.
The study of pharmacologic agents and pathophysiologic states requires a
technique of measuring the tissue blood flow in internal organs, in the
microvascular bed of the skin and the like, its distribution in different
regions of the tissues, and its variation with time. This is especially
true in the kidney, where interarenal redistribution of flow is one of the
major effects of drugs and hemodynamic changes.
Known techniques of measuring regional renal blood flow include radioactive
indicator washout, implanted hydrogen electrode indicator dilution
technique, autoradiography, angiography, implantation of .beta.-ray
detectors and radioactive microsphere trapping. Each of these known
techniques has serious drawbacks for the monitoring of tissue perfusion
during physiologic experiments. The radioactive tracer washout can be used
dynamically, but there is doubt as to the localization of the abstract
compartments which it defines, and whether this localization is the same
in all physiologic states. The hydrogen electrode method is invasive, and
may cause alterations in local flow. The same applies to implantable
radiation detectors. The radioactive microsphere method is precise and
localized, but it is destructive, and only a small number of data points
may be taken in a single subject. It cannot be used to study dynamic
changes in real time. The same is true of autoradiography. Angiography is
not quantitative and requires the injection of contrast media which may
disturb renal function.
It has been proposed in U.S. Pat. No. 3,511,227 to C. C. Johnson entitled
"Measurement of Blood Flow Using Coherent Light" issued May 12, 1970 that
the rate of blood flow within a blood vessel can be determined by
measuring the Doppler frequency shift of coherent radiation, which can be
produced by a laser, by directing a coherent light beam into the blood
stream of a patient, and comparing the frequency of the scattered light
radiation with the frequency of the original beam, the difference being a
measure of the blood flow rate. This technique may be suitable for
measuring the flow rate within a relatively large vessel, using an optical
catheter or needle, or in some cases, by selecting a given wavelength
which will penetrate the vessel with a venipuncture. On the other hand,
the technique cannot be used accurately to measure the velocity of motion
of red blood cells in a microvascular bed of an organ, for example, to
measure the local renal cortical blood flow parameter or the local
cutaneous blood flow parameter.
It has been reported, on the basis of preliminary experiments, that if the
coherent monochromatic light of a laser is used to illuminate tissues, the
light scattered from the tissue has a broadened spectrum. The broadening
is believed to be a result of the Doppler frequency shift sustained by
light when it is scattered from red cells moving in the microvessels. See
Stern, "In vivo evaluation of microcirculation by coherent light
scattering", Nature, Vol. 254, pages 56-58, March 1975.
SUMMARY OF THE INVENTION
It is the principal object of the present invention to provide a method of
and apparatus for measuring the flow of moving material which utilize the
reported phenomenon of spectrum broadening of coherent monochromatic light
scattered from the material.
It is an object of the present invention to provide a method of and
apparatus for measuring blood flow in tissue having a vascular bed which
do not require the use of radioactive materials.
It is another object of the present invention to provide a method of and an
apparatus for measuring blood flow in tissue having a vascular bed which
avoid invasive procedures of the site.
It is an additional object of the present invention to provide an apparatus
for and a method of measuring blood flow in tissue having a vascular bed
which can be continuous and effects a quantitative measure of the flow.
It is a further object of the present invention to provide an apparatus for
and method of measuring blood flow in tissue having a vascular bed which
involves the use of the coherent monochromatic light of a laser.
It is yet another object of the present invention to provide an apparatus
for and a method of measuring blood flow in tissue having a microvascular
bed which determine blood flow as a function of Doppler frequency shifts
of coherent monochromatic light scattered from red blood cells moving in
microvessels in the bed.
It is yet an additional object of the present invention to provide an
apparatus for and a method of measuring the flow of blood flowing in
tissue which utilize the reported phenomenon of spectrum broadening of
coherent monochromatic light scattered from tissues.
The foregoing objects, as well as others which are to become apparent from
the text below, are achieved in accordance with an exemplary embodiment of
the present invention, in its apparatus aspect, by providing a continuous
wave laser, optics for illuminating a region of tissue, optics for
retrieving scattered light, a pinhole mask for selecting one coherence
area of the scattering pattern, a filter to protect against room light, a
photo-detector such as a photomultiplier tube or a photodiode and
circuitry for processing and analyzing the output of the photo-detector.
The circuitry includes, a differentiator, a low pass filter and a weighted
averaging detector, preferably a root-mean-square (RMS) detector,
connected in cascade between the photo-detector and a flow parameter
calculating circuit. The flow parameter calculating circuit also receives
a second output from a linear, averaging amplifier coupled between the
calculating circuit and the photo-detector, this amplifier providing an
output signal representative of the mean current from the photo-detector.
The calculating circuit is designed to solve the equation F =
.sqroot.R.sup.2 - SI, where R is the output from the RMS detector, and S
is a constant representing shot noise and I is the mean photo-detector
current of the photo-detector.
In a preferred variant the calculating circuit also effects an arithmetic
division of F by I, providing F.sub.norm, the normalized flow parameter.
The method of the present invention can be carried out using the
above-described apparatus. The method involves illuminating a region of
tissue having a vascular bed with coherent light; retrieving light
scattered by the tissue, this light having a broadened spectrum caused by
moving blood cells in the tissue; producing a reduced frequency spectrum
of signals by beating the received light signals in a nonlinear
photo-detector; passing the reduced frequency spectrum of signals through
a low-pass filter and a differentiator; obtaining a weighted average R of
the frequency spectrum of signals passed through the differentiator,
preferably obtaining the RMS valve thereof; determining the mean current I
produced by the nonlinear photo-detector; and performing the following
calculation: F = .sqroot.R.sup.2 -SI where F is the flow parameter and S
is a constant determined by the gain of the photo-detector.
In a preferred variant of the method F is divided by I to provide
F.sub.norm, the normalized flow parameter.
The present invention, in its apparatus aspect, is broadly characterized by
means for sensing backscattered light from moving material, means for
determining the spectrum broadening of the sensed backscattered light and
circuitry which processes signals produced to develop a signal
representative of flow parameter.
In its method aspect, the present invention is broadly characterized by
sensing the backscattered light, determining the spectrum broadening and
developing a signal representation of flow parameter.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic diagram of an experimental set-up used in studying
local blood flow in the outer cortex of a rat kidney using laser Doppler
spectroscopy and incorporating an exemplary embodiment of an apparatus
according to the present invention.
FIG. 2 is a graphical representation of a family of Doppler spectra
obtained from the kidney of a rat using the apparatus of FIG. 1 while
infusing the rat with norepinephrine.
FIG. 3 is a graphical representation of steady state dose responses
obtaining from the kidneys of three rats using the apparatus of FIG. 1,
the rats having been intravenously supplied with norepinephrine.
FIG. 4 is a graphical representation of physiologic data, including the
transient response of the renal flow parameter, obtained from a rat using
the apparatus of FIG. 1, over a period including a short span during which
the rat was injected intravenously with norepinephrine.
FIG. 5A and 5B are respectively graphical representations of renal cortical
flow parameters in six rats under control state conditions and when
subjected to hydrolazine given intravenously followed by dextran 70
obtained using the apparatus of FIG. 1.
FIG. 6 is a graphical representation of renal cortical flow parameters,
obtained from two rats, using the apparatus of FIG. 1, while subjecting
the rats to intravenous angiotensin II, one of the rats being subjected
simultaneously to infusion of the inhibitor saralasin (P113).
FIG. 7 is a graphical representation of an experimental spectrum like that
of one of the curves shown in FIG. 2 and of an idealized theoretical
spectrum obtained mathematically.
FIG. 8 is a schematic diagram of an analog calculation circuit suitable for
use as the flow parameter calculation circuit shown in FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Before turning to FIG. 1 and a consideration in detail of the experimental
set-up shown therein, which set-up incorporates an embodiment of an
apparatus for measuring the flow parameter of blood flowing in tissue, a
brief consideration of the principles upon which the present invention is
based is in order.
When coherent light, as a practical matter supplied by a suitable laser, is
scattered by a moving blood cell, its frequency is altered by an amount
.DELTA..omega. = K.multidot.v where K and v are respectively the
scattering vector of the light and the velocity vector of the red cell.
The superimposition of the light scattered by red cells of different
velocities and at different angles gives rise to an overall broadening of
the spectral line of the backscattered light. Because of the multiple
scattering of light in tissues by the red cells, neither the angle of
incidence at any given red cell nor the angle of scattering of the light
can be controlled by the geometry of the apparatus. In addition, at least
some of the light may be scattered by more than one red cell, thereby
sustaining more than one Doppler shift. For these reasons the spectrum of
light scattered from a complex structure, such as a perfused kidney or the
like, in theory at least cannot at present be exactly predicted. However,
if the overall flow pattern is speeded up or slowed down, the overall
linewidth of the spectrum will scale in the same way as the velocity
distribution of the red cells, because this amounts in essence to changing
the time scale of the flow pattern. This has been demonstrated
experimentally for blood in capillary tubes, and applied with great
generality.
If the scattered light is allowed to fall on a photodetector such as a
photodiode or photomultiplier tube, the various Doppler shifted components
beat with one another to produce fluctuations in the photocurrent at audio
frequencies. If there is a dominant component of light scattered from
stationary stroma, as is clearly true for skin, and true at least under
some conditions for a renal cortex, this scattered light can serve as a
reference carrier, and the spectrum of the beat frequencies will have the
same shape as the spectral line of the light; that is, a heterodyne
spectrum results. If all the scattered light comes from the red blood
cells, the different Doppler components beat with one another and a
homodyne spectrum results. This spectrum is the self-convolution of the
heterodyne spectrum, and wider by a factor of .sqroot.2. In either case,
or any intermediate case in which both homodyne and heterodyne spectrums
result and are superimposed as a composite spectrum, the composite
photocurrent spectrum scales in width like the velocity distribution of
red blood cells.
One measure of the linewidth is the root-mean-square (RMS) bandwidth
F = .sqroot..intg.P(.omega.).omega..sup.2 d.omega. (1)
where P (.omega.) is the power spectrum of the photocurrent from a
photodiode or photomultiplier tube. For laminar flow in fixed geometry, F
is directly proportional to flow rate. In more general cases, it can be
considered the product of G .multidot. F.sub.t true blood flow, the
calibration "constant" G in each general case depending on the geometry of
the flow and the optical properties of the tissue which is illuminated.
Since the number F defined by equation (1) already varies directly with
the amount of light scattered by red blood cells, and therefore with the
amount of blood in the tissue, it scales like flow in this respect also,
and it is reasonable to expect that the factor G will not vary greatly in
any one tissue in the course of ordinary changes of physiologic state.
This will certainly be the case for changes due to vasomotion occurring
outside the region of observation and at localized sphincters which
contain only a small faction of the red cells in the observation region.
These considerations make it plausible that the parameter F should vary, in
a more or less linear fashion, with tissue blood flow in a given tissue;
moreover, F can be measured continuously by simple analog circuitry not
requiring a spectrum analyzer. As a practical matter, the flow parameter
can be determined as an RMS flow parameter.
Referring to FIG. 1, the experimental set-up for studying local blood flow
in the outer cortex of a kidney of a rat 10 includes a 15mW helium-neon
laser 11 (Jodan Engineering model HN-15) which produces monochromatic,
coherent light having a wave length of 632.8 nm and a beam width of
approximately one mm. The light from the laser 11, as shown, impinges on a
half-silvered mirror 12, which reflects the beam towards the exposed
kidney of the rat 10, to illuminate a spot on the exposed renal cortex.
The kidney is supported by a glass half-ring kidney support 13, which
includes at least one rod member in contact with the surface which
supports the rat 10. The support 13 prevents the kidney from moving to any
appreciable degree during the procedure. The backscattered light passes
firstly through a two mm aperture in a mask 14 at the surface of the
kidney, thence through the half-silver mirror 12 to a second mirror 9
which directs the light which passes through the mirror 12 towards and
through a 0.5 mm pinhole 15 located in a disc 16 positioned approximately
one mm away from the mask 14. It is to be understood that a single,
tilted, fully silvered mirror could be used in place of the two mirrors 9
and 12 and the members 16-18 somewhat differently positioned. The two mm
aperture and the 0.5 mm pinhole restrict the scattered laser light so that
approximately one coherent area of the renal cortex is sampled. It is to
be understood that as a practical matter, light from the laser which
impinges on the surface of the renal cortex at some distances from a
single coherent area, does not have a coherent relationship to the light
from the area sought to be sampled. The backscattered light which passes
through the aperture 15 in the disc 16 is passed through an interference
filter 17 which has a band width approximately 3 nm centered about 632.8
nm, the interference filter 17 centered about the wavelength serves the
purpose of blocking ambient light so as to make the experimental set-up
insensitive to ordinary room lights. The beam of coherent light which
passes through the interference filter 17 is directed through lens 18 onto
the photocathode of a photomultiplier tube 20 having a high quantum
efficiency in the red (EMI 7658-R). While the photomultiplier tube 20 is
utilized in the exemplary embodiment, it is to be appreciated that other
types of photo-detectors, such as a photodiode could be used as well. The
photomultiplier tube 20 like photodiodes, is a non-linear device. The
various Doppler shifted components of the light which impinge of the
cathode of the photomultiplier tube 20 beat with one another to produce
fluctuations in the photocurrent output from the tube 20. The frequency
relationships are such that audio frequency signals are produced as beat
notes so as to provide either a homodyne spectrum, a heterodyne spectrum
or mixed spectrum of audio frequencies, as indicated above. The beat
frequency photocurrent output from the photomultiplier tube 20 is supplied
to a preamplifier 21. The output from the preamplifier 21, in the
experimental set-up is fed to an analog tape recorder 22, which records
the output for possible further study. An output from the preamplifier 21
is also fed to an oscilloscope 23 and to an X-Y recorder 24 via a spectrum
analyzer 25. The X-Y recorder serves the purpose of recording the output
of the amplifier 25 for further study, while the oscilloscope 23 permits
direct viewing of the spectrum during experiments.
In accordance with the apparatus of the present invention, the output from
the preamplifier 21 is fed to an adjustable low pass filter 26, which
passes, for example, frequencies of up to about 20 KHz. The output from
the filter 26 is fed to a conventional differentiator 27 which
differentiates the received audio frequency signals with respect to time.
The differentiated output from the differentiator 27 is fed to a
root-mean-square (RMS) detector 28. As shown, the output from the
root-mean-square detector 28 is fed to a digital voltmeter 29, the output
from the root-mean-square detector 28 being fed additionally to a first
input of a flow parameter calculating circuit 30. The flow parameter
calculating circuit 30 has a second input which is coupled to an output
from a linear, averaging amplifier 31 which has its input coupled to the
output of the preamplifier 21. The linear, averaging amplifier 31 is
preferably adjustable and includes an RC feedback loop, and produces an
output signal indicative of the mean photomultiplier tube current produced
in the tube 20; this output is displayed on digital voltmeter 39.
The flow parameter calculating circuit 30 is an arithmetic, analog circuit
which produces an output representative of the flow parameter, preferably
normalized. The details of construction and operation of the flow
parameter calculating circuit 30 are to be considered further hereinbelow
and are illustrated in FIG. 8.
The output from the root-mean-square detector 28 is fed as one input to a
strip-chart recorder 32, which is provided with four additional inputs.
The output signal from the linear averaging amplifier 31, which represents
the mean photomultiplier tube current is fed to a second input to the
strip-chart recorder 32.
The experimental setup includes additionally an EKG input to the
strip-chart recorder 32 from conventional needle electrodes (not shown)
operatively associated with the rat 10. A conventional rate monitor 33
(Hewlett-Packard 780 7A) is also connected to these electrodes to develop
an output analog signal representing the heart beat rate. A pressure
transducer in the form of a strain gauge monometer 34 (Statham P23 db) is
coupled by a 0.023 inch ID polyetheylene tubing 35 to the carotid artery
of the rat 10 so as to produce an output signal representative of the
arterial blood pressure, this signal being coupled to a further input of
the strip-chart recorder 32. The trachea of the rat 10 is cannulated with
a 3 cm No. 12 thin walled polyethylene tubing 36. During experimental
procedure using the setup illustrated in FIG. 1, the arterial blood
pressure, EKG, analog heart rate, mean photomultiplier tube current and
the root-mean-square detector output signals are continuously and
simultaneously recorded for further study on the strip-chart recorder 32.
The infusion pumps 37 and 38 are connected respectively to the internal
jugular vein and to the femoral vein of the rat 10 via a 0.11 inch ID
polyethylene tubing 40 and appropriately sized polyethylene tubing 41 so
that the rat may be infused or injected with various material during
experimental procedures.
The actual photocurrent from the photomultiplier tube 20 contains, in
addition to the flow signal, a certain irreducible amount of shot
noise--noise which is due to the quantum nature of light, has a perfectly
white spectrum, and is uncorrelated with the signal, to which it therefore
adds in quadrature. Also, the total signal amplitude is proportional to
the amount of light returned from the kidney of the rat 10, which may vary
somewhat due to drift in power of the laser 11 and variations in the color
of kidneys. To compensate for these effects, the actual, normalized flow
parameter is computed by the calculating circuit 30 from the output of the
root-mean-square detector 28 and from the linear amplifier 31 by the
equation
##EQU2##
where R is the RMS detector output, I is the mean photocurrent and S is
the shot noise constant. This assures, among other things, that the
variations in F are not due to changes in the color of the tissue. It is
to be understood that if a normalized output is not desired, the
computation need not include the final arithmetic division by I. The shot
noise constant S depends on the gain of the photomult | | |
