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Claims  |
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What is claimed is:
1. A spectrophotometric reflectance method for measuring local metabolism
of a body organ such as the brain, in situ, in vivo, non-invasively,
atraumatically, harmlessly, rapidly and continuously, said method
comprising the steps:
(a) locating and fixing the body in a position appropriate to the measuring
operation;
(b) selecting an optical transmission-reflectance path including said organ
and extending for several centimeters between points of light entry and
exit said points of light entry and exit being laterally spaced several
centimeters apart and positioned on contiguous skin surface areas of the
body;
(c) establishing a plurality of near-infrared light sources located
external of the body and having light emissions of different wavelengths
in the 700 to 1300 nanometer spectral range and of an intensity below the
level damaging to the body and said organ but sufficient to be detectable
by a light sensor after transmission through any skin, bone and tissue
included in said path and scattering in and reflectance from said organ
along said path, said emissions including at least one measuring
wavelength and at least one reference wavelength within said spectral
range, each said measuring wavelength being selected such that said organ
exhibits a selective absorption therefor, the extent of which is dependent
upon a specific state of metabolic activity of said organ;
(d) directing said light emissions at said measuring and reference
wavelengths sequentially at said point of entry to be transmitted,
reflected and scattered along said path and to said organ and receiving
the light emissions reflected directly back from said skin, bone and
tissue at or within a few millimeters of said point of entry as well as
the light emissions reflected and scattered from said organ at a point
several centimeters away from said point of entry and light sensor and
circuit means adapted to produce and electrical output signal corrected
for changes in blood volume of said skin, bone and tissue during the
measuring cycle and representing the difference in absorption of said
measuring and reference wavelengths by the organ as a function of the
state of said metabolic activity; and
(e) converting said electrical output signal to a signal providing a
substantially continuous and rapid measure of said activity.
2. The method of claim 1 wherein said organ is the brain.
3. The method of claim 1 including the step of receiving said light
emissions reflected back from said skin, bone and tissue at said point of
entry in light receptor means structurally combined with light
transmission means connected to said light sources and removably secured
to the body at said point of entry.
4. The method of claim 1 including the step of utilizing said light
emissions reflected back from said skin, bone and tissue to correct for
variations in output of said light sources during said measuring
operation.
5. The method of claim 1 wherein said organ comprises the brain, said
points of light entry and exit comprise spaced points on the head of the
body having the brain organ being measured and including the step of
sensing and electrically processing said light emissions reflected back at
said point of entry in a manner enabling reflected and scattered light
received at said exit point mainly from the skin and bone of the head to
be discriminated from reflected and scattered light received at said more
distant exit point from the gray and white matter of the brain whereby in
said processing said signal is developed as indicative of oxygen
sufficiency in said gray matter.
6. The method of claim 1 including at least two reference wavelengths
comprising a contrabestic pair and processing the sum of the absorption
changes at the two contrabestic wavelengths to produce a signal indicative
of blood volume changes and using the difference of the absorption changes
in said wavelengths to produce a signal indicative of changes in
oxygenation of the blood in said organ.
7. The method of claim 1 wherein each respective said measuring wavelength
is selected within an absorption band of a metabolite, enzyme or other
cellular biochemical entity controlling said state of activity and wherein
each said reference wavelength to which a respective measuring wavelength
is referred is selected so as to be more distant from the peak of the
respective said band within which such respective wavelength resides.
8. The method of claim 1 wherein said activity is one of cellular
metabolism.
9. The method of claim 8 wherein said activity is that of the redox state
of enzyme cytochrome a, a.sub.3.
10. The method of claim 8 wherein said activity is that of hemoglobin
oxygenation in said organ.
11. The method of claim 1 wherein said activity relates to local changes in
blood volume in said organ.
12. The method of claim 1 including the step of periodically interrupting
normal measuring of said metabolism by admitting an agent to said body in
a manner enabling such agent to reach said organ and designed to effect a
fluctuating change of the absorption properties within said organ over a
period of time effecting a corresponding change in said electrical output
signal during such time, and recording the intensity of said fluctuating
change and the time interval between the beginning and end of said change
in the output signal brought about by said agent within said organ as a
measure of the blood flow rate to said organ.
13. The method of claim 12 wherein said agent comprises a dye agent.
14. The method of claim 12 wherein said agent comprises a gaseous agent.
15. The method of claim 1 wherein said activity is that of the redox state
of enzyme cytochrome a, a.sub.3 in said organ.
16. The method of claim 1 wherein said activity is that of hemoglobin
oxygenation in said organ.
17. The method of claim 1 including at least two said reference wavelengths
comprising a contrabestic pair or series.
18. A spectrophotometric reflectance apparatus for measuring in situ, in
vivo, non-invasively, atraumatically, harmlessly, rapidly and continuously
a local metabolic, oxygen dependent activity of a body organ such as the
brain of a body where such activity bears a measurable relation to an
oxygen dependent absorption characteristic of the organ for a particular
wavelength of light transmitted therethrough, comprising:
(a) light source means including:
(i) a plurality of near-infrared light sources located external of the body
and having light emissions of different wavelengths in the 700 to 1300
nanometer spectral range and of an intensity below the level damaging to
the body and said organ but sufficient to be detectable by a light sensor
after transmission through any skin, bone and tissue included in an
optical transmission-reflectance path including said organ and extending
for several centimeters between points of light entry and exit laterally
spaced several centimeters apart and located on contiguous skin surface
areas of the body and after scattering in and reflectance from said organ
along said path, said emissions including at least one measuring
wavelength and at least one reference wavelength within said spectral
range, each said measuring wavelength being selected such that said organ
exhibits a selective absorption therefor, the extent of which is dependent
upon a specific state of a local metabolic, oxygen dependent activity of
said organ;
(ii) means operatively associated with said light sources to produce
emissions representing at least one said measuring wavelength and at least
one said reference wavelength within said spectral range for transmission
along said path to said organ and at levels of intensity below that which
would be damaging to the body and said organ; and
(iii) light transmission means for receiving, transmitting and directing
the output light emissions of said light sources at said measuring and
reference wavelengths to a selected fixed light entry point on said body
to be transmitted, reflected and scattered along said path and to said
organ;
(b) first detector means fixed to said body proximate said entry point for
receiving and transmitting the light emissions reflected directly back
from said skin, bone and tissue at or within a few millimeters of said
point of entry;
(c) second detector means fixed to said body at a fixed light exit point on
said body and spaced several centimeters away from said fixed light entry
point for receiving and transmitting the light emissions reflected and
scattered from said organ;
(d) light sensor and circuit means connected to receive the light emission
outputs of said first and second detector means and adapted to produce an
electrical output signal corrected for changes in blood volume of said
skin, bone and tissue during the measuring cycle and representing the
difference in absorption of said measuring and reference wavelengths by
the organ as a function of the state of said local metabolic oxygen
dependent activity; and
(e) means for converting said electrical output signal to a signal
providing a substantially continuous and rapid measure of said activity.
19. The apparatus of claim 18 wherein said means operatively associated
with said light sources comprises means for sequentially operating said
light sources.
20. The apparatus of claim 18 wherein said light transmission and first
detector means are structurally combined and removably secured to the body
at said point of entry.
21. The apparatus of claim 18 wherein said light sensor and circuit means
include means for utilizing said light emissions reflected back from said
skin, bone and tissue at said point of entry to correct for variations in
output of said light sources during said measuring operation.
22. The apparatus of claim 18 wherein said organ comprises the brain in the
head of said body, said points of light entry and exit comprise spaced
points on the head and wherein said light sensor and circuit means include
means adapted for sensing and electrically processing said light emissions
reflected back at said point of entry in a manner enabling reflected and
scattered light received at said exit point mainly from the skin, bone and
tissue of the head to be discriminated from reflected and scattered light
received at said more distant exit point from the gray and white matter of
the brain whereby in said processing said signal is developed as
indicative of oxygen sufficiency in said gray matter.
23. The apparatus of claim 18 wherein said light sources and said means for
sequentially operating said light sources produce at least two reference
wavelengths comprising a contrabestic pair and said light sensor and
circuit means are adapted for processing the sum of the absorption changes
at the two contrabestic wavelengths to produce a signal indicative of
blood volume changes and being further adapted for using the difference of
the absorption changes in said wavelengths to produce a signal indicative
of changes in oxygenation of the blood in said organ.
24. The apparatus of claim 18 wherein said activity is one of cellular
metabolism and said wavelengths operate in reference thereto.
25. The apparatus of claim 18 wherein said activity is one of cellular
oxidative metabolism and said wavelengths operate in reference thereto.
26. The apparatus of claim 18 wherein said activity is that of the redox
state of enzyme cytochrome a, a.sub.3 and said wavelengths operate in
reference thereto.
27. The apparatus of claim 18 wherein said activity is that of hemoglobin
oxygenation in said organ and said wavelengths operate in reference
thereto.
28. The apparatus of claim 18 wherein said activity is that of local
changes in blood volume in said organ, including means for establishing a
feedback voltage to maintain at some predetermined level the said
reference signal corresponding to a selected said reference wavelength and
monitoring said voltage as a measure of said volume.
29. The apparatus of claim 18 wherein said measured activity is that of the
redox state of enzyme cytochrome a, a.sub.3 in said organ.
30. The apparatus of claim 18 wherein said light sources and means for
operating said light sources are adapted to produce a pair of said
reference wavelengths comprising a contrabestic pair. |
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Claims |
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Description |
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention pertains to a spectrophotometric reflectance method and
apparatus for monitoring metabolism and is illustrated as monitoring
cellular oxidative metabolism by conducting non-invasive, in vivo,
harmless, continuous in situ measurements of changes in the steady state
oxidation-reduction of cellular cytochromes together with changes in skin
and bone blood volume, in organ blood volume, the oxygenation state of
hemoglobin and the rate of blood flow in a vital organ such as the brain,
heart or kidney, in other organs, in limbs or other parts of a living
human or animal body.
2. History of the Prior Art
An extensive and useful history of the prior art is given in the
referred-to copending application, Ser. No. 810,777 and which is deemed
incorporated herein by reference to avoid repetition of the same.
As was pointed out in such description of the prior art, while
circulatory-respiratory functions, arterial blood oxygenation and blood
samples, per se, have been monitored by spectrophotometric techniques,
presently existing methods are not suited for assessing the sufficiency of
oxygen and metabolism in general in such vital organs as the brain and
heart. Further, such prior methods do not provide precise information and
are often traumatic as well. Consequently, an obvious need exists for a
method by which this life sustaining parameter, i.e., cellular oxidative
metabolism, can be measured in vivo, in situ and monitored continuously
with precision and in a non-invasive, non-traumatic manner. Equally
important is a need to be able to monitor blood volume and blood flow rate
of the organ being monitored.
In order to distinguish and understand the invention of the present
application, a summary of the invention of the copending application Ser.
No. 810,777 is restated here for reference as what is regarded as the most
pertinent prior art.
It is known that the cellular enzyme cytochrome a, a.sub.3 (also known as
cytochrome c oxidase) has a key role in oxidative metabolism. That is, it
has been established that the enzyme interacts directly with oxygen and
mediates the release of energy during the reduction of O.sub.2 to H.sub.2
O. This is achieved by the catalytic donation of four electrons to O.sub.2
and subsequent combination with four H+ ions. Under conditions of an
inadequate O.sub.2 supply, electrons accumulate and the enzyme population
shifts to a more reduced steady state. Consequently, an ability to
continuously measure and monitor the redox state of this oxygen utilizing
enzyme in vivo, in situ would provide decisive information on the
parameter of oxygen sufficiency in any tissue or organ in question. The
invention of the copending application Ser. No. 810,777 provided that
capability as well as the capability to monitor blood volume and blood
flow rate in a manner which is non-invasive and atraumatic.
In the invention of the copending application Ser. No. 810,777, this was
accomplished by optical techniques, the application of which was made
possible by observing that the body and its organs are relatively pervious
to low level, non-hazardous light energy in the near infrared region of
the spectrum. Of particular importance, it was discovered that a beam of
relatively low level, non-intense radiation in reference and measuring
wavelengths of from about 700-1300 nm can penetrate, reach the organ and
be detected and monitored at the end of a relatively long optical path in
any selected portion of a human or animal body, which path includes bone
as well as soft tissue. While such operating principles were illustrated
in a manner indicating them to be useful in either a transillumination or
a reflectance technique, emphasis was given in the invention of copending
application Ser. No. 810,777 to a transillumination technique whereas in
the present invention and application emphasis is given to use of the same
basic principles in a reflectance technique.
By fortunate coincidence, cytochrome a, a.sub.3 has radiation, absorption
properties in the aforenoted spectral region, the character of which
varies according to its oxidation state. Thus, the invention of the
copending application recognized that it is possible to monitor the redox
state of this oxygen utilizing enzyme by a spectrophotometric method not
known to the art prior to the invention of the copending application.
The spectrophotometric measurements, according to the invention of the
copending application were made in vivo by transmitting near infrared
radiation in at least two different and periodically recurring wavelengths
to the test organ, in situ, and detecting and measuring the radiation
intensity which emerged for assessment of biochemical reactions utilizing
the Beer-Lambert Law as referred to in the copending application. One of
the wavelengths selected was in a range at which oxidized cytochrome a,
a.sub.3 is highly absorptive. One or two additional wavelengths outside
the peak of the cytochrome absorption band, but preferably in relatively
close proximity to the measuring wavelength were presented in sequence to
provide one or more reference signals. A simple subtraction or ratio
calculation between the measuring and reference signals was achieved by
appropriate circuitry and the non-specific changes in the intensity of
transmitted radiation not attributable to absorption by cytochrome a,
a.sub.3 were eliminated.
Although the capability for continuously monitoring cellular oxidative
metabolism by monitoring the redox state of cytochrome a, a.sub.3 in the
cells of the selected organ was of principal interest to the invention of
the copending application Ser. No. 810,777, ancillary data on circulatory
parameters related to functioning of the organ was also shown to be
obtainable. As an example, it was shown that the oxygenation state of the
blood supplied to a given organ can be monitored by the hemoglobin band at
slightly different wavelengths, e.g., 740-780 nm, in the aforenoted near
infrared region of the spectrum. Likewise, data on the total blood volume
of the organ was shown to be obtainable by monitoring a hemoglobin (Hb)
oxyhemoglobin (HbO.sub.2) isobestic point. This well-known
spectrophotometric term refers to a wavelength at which two forms of the
same molecule or mixture of molecules have equal absorption intensity.
Thus, for oxygenated and disoxygenated hemoglobin, such a point was found
to occur variously between 810 and 820 nm. This variation of stated
wavelengths derives from problems arising from the very low optical
densities of Hb and HbO.sub.2 in this range and the relative insensitivity
of most commonly available spectrophotometers in this wavelength range. In
practice, any wavelength in the entire range of 815.+-.5 nm was stated to
be useful without jeopardy to the results in situations where the
measurements are less sensitive to small errors. As further pointed out in
the copending application, a yet wider range of wavelengths can serve the
purpose since even small blood volume changes will outweigh the possible
interference by Hb.revreaction.HbO.sub.2 shifts. In another approach
described in the copending application, the less practiced technique of
combining two wavelengths with opposite optical density (OD) responses to
the interfering reaction can be combined. Thus, for
Hb.revreaction.HbO.sub.2 equal .DELTA.OD values but of opposite sign were
shown to occur at 786 and 870 nm. This combination of signals of equal
strength but opposite sign at two wavelengths is called a "contrabestic
pair". It is especially useful when two reference wavelengths are used
straddling the peak to be measured in conditions of intense and changing,
wavelength dependent scattering. A series of wavelengths chosen such that
the net sum of their optical density changes becomes zero is another
method of practicing the cancellation of interfering reactions. In
contradistinction, "equibestic" pairs can be used to correct for errors
arising when the spectral effects of a Hb to HbO.sub.2 shift or the
reverse predominate. In the case of the invention of the copending
application, a reference wavelength was selected which has an equal OD
effect in the same direction as the one occurring at the measuring
wavelength when the interfering reaction proceeds.
In addition, blood flow rates in the invention of the copending application
were monitored, albeit discontinuously, by the rapid administration of a
small quantity of a dye, e.g., "cardiogreen", having absorption properties
in the near infrared spectral region or alternatively by having the test
subject take single breaths of a gas mixture containing a high and low
concentration of oxygen in alternating sequence or one breath of a mixture
with a small, innocuous admixture of CO. By selecting two wavelengths for
differentially measuring the optical density of the organ in the spectral
region of the absorption band of the dye, an optical signal indicating the
arrival and subsequent departure of the dye in the cerebral circulation
and dilution in the total blood volume, the so-called transit time, was
measured. The latter was stated in the copending application to be
directly indicative of the rate of blood flow as proven by Zierler (see
the book "PRINCIPLES OF APPLIED BIOMEDICAL INSTRUMENTATION"). Similarly,
in the invention of the copending application, the optical density
differences of the hemoglobin compounds (HbO.sub.2, HbCO or other) were
described as useful to provide the optical signal when the inspired air is
suddenly and briefly varied. Having restated a summary of the invention of
copending application Ser. No. 810,777, a summary of the present invention
will be given.
SUMMARY OF THE INVENTION
Using the foregoing summary of the prior invention set forth in copending
application Ser. No. 810,777 as a reference, it may be succinctly stated
that the present invention is directed to a unique spectrophotometric
reflectance method and apparatus for measuring oxidative metabolism
utilizing the basic discoveries set forth with regard to the prior
invention. As with the prior invention, the method of the present
invention utilizes a beam of relatively low level, non-intense radiation
in reference and measuring wavelengths of from about 700-1300 nm. As with
the prior invention, the present invention provides an ability using a
reflectance method to monitor cellular metabolism as a means of measuring
local metabolism in a continuous, harmless, non-invasive manner. The
spectrophotometric measurements, according to the present invention, are
made by transmitting near-infrared radiation in at least two different and
periodically recurring wavelengths to the test organ, in situ, and
detecting and measuring the radiation intensity which emerges at a point
spaced from the point of light entry for assessment of biochemical
reaction utilizing the Beer-Lambert Law in the same manner as in the prior
invention.
As disclosed in a specific embodiment, the present invention is shown
applied to the measurement of oxygen sufficiency in the brain. The light
source and light detector are spaced apart on the same side of the head.
The method provides for detecting light reflected back to the light source
location and using this as a correction for skin blood volume changes. The
method also provides for discriminating between light scattered by the
gray matter and reflected from the white matter of the brain and providing
a signal known to be indicative of the oxygen sufficiency in the gray
matter of the brain.
While the prior invention of copending application Ser. No. 810,777 met all
of its expectations, the method of the present invention as compared to
the method of the prior invention has the advantage of requiring less
complexity in the equipment and also should be expected for many
applications to provide better localization of the area from which signals
are obtained. Thus, while the method of the prior invention is expected to
maintain its usefulness for many of the numerous applications for
measuring local metabolism in the living human body, the present invention
is likewise expected to exhibit special advantages in other applications
such as measuring oxidative metabolism in the living human brain in a
manner not heretofore accomplished.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is intended to represent the head of a living human patient and
illustrating the general method of the invention.
FIG. 2 is a plot of the relation of the distance between light entry and
exit locations to the signal voltage and the source of the measured light.
FIG. 3 diagrammatically illustrates the general method of the invention as
applied to the head of a human or animal, in vivo.
FIG. 4 represents a cross section through the combined light source and
reference detector bundle.
FIG. 5 is a representation of the reduction of Cu.sub.L of cytochrome a,
a.sub.3 and decrease of intracranial blood volume during one minute of
hyperventilation, the illustrated cytochrome response being deemed fairly
typical while the return of the blood volume trace is more variable but
often returns more rapidly to the baseline than illustrated.
FIG. 6 illustrates the effect of hypercapnia plus hyperoxia produced by
breathing 5% CO.sub.2 plus 95% O.sub.2 for 90 seconds. Here it should be
noted that a long term increase of the base line, as shown, is often
recorded after the first episode. The effects of the second and later
exposures to the gas mixture tend to be superimposed on this new baseline.
FIG. 6A represents a continuation of FIG. 6.
FIG. 7 shows the spectral differences observed when blood changes from
HbO.sub.2 to Hb and indicates a contrabestic pair from which blood volume
changes as well as oxygenation changes may be determined according to the
method of the invention.
DETAILED DESCRIPTION OF THE INVENTION
A salient feature of the present invention, as with the invention of
copending application Ser. No. 810,777, is the observation that light
energy in the near infrared region having wavelengths in the range of from
about 700-1300 nm and at a relatively low, non-hazardous intensity can be
made to penetrate and be reflected and scattered from both soft tissue and
bone surrounding a living organ as well as penetrate and be reflected and
scattered from the organ itself and in relatively long optical paths and
the detected light at the end of the paths can be collected and related to
oxidative metabolism. This wavelength range has also been proven critical
since within the 700 to 1300 nm wavelength range oxygenated hemoglobin
(HbO.sub.2) has extremely low absorption characteristics, whereas
deoxygenated hemoglobin (Hb) displays some weak absorption which slowly
rises with decreasing wavelengths below 815 nm to a small peak in
absorption around 760 nm. Because of these optical properties, the
Hb-HbO.sub.2 steady state (i.e., the venous-arterial average) can be
monitored.
In addition and of significant importance, the present invention recognizes
that cytochrome a, a.sub.3 in living body tissue also exhibits an oxygen
dependent absorption band in the 700 to 1300 nm wavelength range of the
spectrum. When this key enzyme in oxidative reactions is in the presence
of sufficient oxygen, a weak absorption band exists in the 780 to 870
region with a maximum at a wavelength of about 820 to 840 nm. The absence
of oxygen results in a complete reduction of the enzyme and a concomitant
disappearance of the absorption band. The present invention provides a
spectrophotometric reflectance method by which this characteristic may be
monitored to monitor oxygen sufficiency in the enzyme.
Cytochrome a, a.sub.3 is the terminal member of the mitochrondrial
respiratory chain and functions as a donor of four electrons to molecular
oxygen in the final step of the main pathway of oxidative metabolism in
the cells. In this reaction, the electrons are transferred to oxygen from
the four metallic redox components of the enzyme, the two iron atoms of
the a and a.sub.3 hemes and two copper atoms. Subsequent or concomitant
combination with four hydrogen ions leads to the formation of H.sub.2 O.
The free energy difference between the hydrogens in the metabolic
substrates and in H.sub.2 O is partially conserved in the form of high
energy phosphate bonds through the oxidative phosphorylation of adenosine
diphosphate (ADP) to adenosine triphosphate (ATP). The latter compound
serves as the primary free energy carrier in the cell and meets the free
energy needs of most of the endergonic reactions required for normal
physiological function and cell survival. Since better than 90 percent of
cellular ATP production is by means of oxidative phosphorylation and since
oxygen utilization is ultimately governed by the rate of transfer of
electrons to oxygen from cytochrome a, a.sub.3, this enzyme performs a
critical role in cellular oxidative metabolism and energetics. In the
absence of sufficient O.sub.2, electrons accumulate in cytochrome a,
a.sub.3, producing a more reduced steady state. Thus, the invention
recognizes that direct measurements on the redox state of this enzyme will
provide conclusive data on the adequacy of oxygen availability and its
utilization in living tissue and organs. The spectrophotometric
reflectance method of the present invention provides a method for
obtaining such measurements.
In carrying out a continuous, non-invasive, in vivo, in situ monitoring of
the redox state of cytochrome a, a.sub.3, near-infrared radiation of
appropriate wavelengths and at a relatively low power level and
corresponding relatively low density is presented at one site and is
transmitted to and reflected from the organ under investigation, and the
reflected and scattered light emerging from laterally-spaced exit is
conducted to a photomultiplier tube or other photodetector for detection
and measurement.
The monitoring, as in the prior invention, may be conducted in either a
dual or triple wavelength mode with one of the wavelengths being selected
to provide a measuring signal and the others a reference signal as
illustrated in the copending application Ser. No. 810,777. The measuring
wavelength is preferably at about 840 nm, the center of the cytochrome a,
a.sub.3 absorption peak observed in vivo, but the choice is not so limited
since other wavelengths in the absorption band can be utilized.
By calculating the difference between the measuring and reference signals,
the non-specific changes in the reflectance characteristics not
attributable to cytochrome absorption are in effect cancelled out.
Appropriate electronic circuits may be used to amplify and demodulate the
separate signals, convert them to DC current and subtract them for a
differential recording in the manner set forth in the prior copending
application.
In one version of the dual mode, the isobestic point of Hb-HbO.sub.2 at 815
nm.+-.5 nm is used as the reference wavelength with a feedback control on
the signal produced to compensate for changes in blood volume. That is, a
negative feedback circuit, for example, connected to the high voltage
source which supplies the photomultiplier tube is used to compensate the
reference signal for changes in the reference signal level caused by blood
volume changes in the tissue being monitored. The voltage adjustment is
then maintained in the subsequent interval when the measuring wavelength
is transmitted. Since the changes in voltage supplied to the
photomultiplier are directly proportional in magnitude to the changes in
blood volume over the optical path, in effect they measure this important
circulatory parameter and are recorded.
In the triple wavelength mode, three wavelengths are presented, i.e., the
measuring wavelength and two reference wavelengths. Desirably, the
reference wavelengths straddle the measuring wavelength and are in
relatively close proximity to it. A suitable choice would be for one
reference wavelength to be about or less than, say, 75 nm lower than the
measuring wavelength and the other to be about or less than 75 nm higher.
When interference by blood volume changes is present, resort is made to a
contrabestic pair for the two reference wavelengths. When
Hb.revreaction.HbO.sub.2 changes predominate over blood volume changes an
equibestic pair is employed.
As has been noted supra, hemoglobin also possesses oxygen dependent
absorption properties in the near-infrared region of the spectrum which
permits continuous monitoring of the Hb-HbO.sub.2 steady state. In
practice, advantage is taken of the fact that deoxygenated hemoglobin (Hb)
exhibits a relatively weak absorption which slowly rises with decreasing
wavelengths below 815 nm to a small peak in the vicinity of about 760 nm.
Thus, determinations on the Hb-HbO.sub.2 steady state can be made by
differential measurements at wavelengths of about 760 nm to 815 nm, with
the 815 nm wavelength (Hb-HbO.sub.2 isobestic point) serving to provide
the reference signal.
As can be seen from the immediately foregoing description, the
spectrophotometric reflectance method of the present invention is adapted
to utilize the discoveries and measuring techniques of the prior
invention. The description now turns to pointing out the more distinctive
features of the present invention as compared to the prior invention. To
illustrate this comparison, the drawings are directed to application of
the method of the present invention to measuring local metabolism in the
brain of a living human or animal specimen, i.e., in vivo, harmlessly,
non-invasively, continuously and rapidly.
As schematically illustrated in FIGS. 1, 3 and 4, two spaced-apart
locations are chosen, one of which is designated as a point of light entry
20 and the other of which is designated as a point of light exit 21.
Advantageously, any bare or bald skin area of sufficient size (1 cm.sup.2
approximately) can be used as an entry or exit site without preparation.
As will later be explained in reference to FIG. 2, the spacing between the
light entry point 20 and light exit point 21 is critical for purposes of
the invention and particularly so in reference to utilizing the invention
in the manner described for measuring local metabolism in the brain of a
living human.
An appropriate source of light 22 provides light within the near-infrared
region of 700-1300 nm spectral range. Light from light source 22 is
transmitted to the light entry location 20 through a fiber optics bundle
assembly 25 having an outer annular fiber bundle assembly 26 surrounding
an inner central smaller bundle assembly 27. The proximal end of the
assembly 25 being located in a tightly pressed position against the light
entry location 20 and secured by a suitable head strap 30 or other
suitable mounting means so as to minimize leakage and loss of light at the
point of entry. The general concentric arrangement of the outer annular
fiber optics bundle 26 and central fiber optics bundle 27 are shown in the
cross section drawing illustrated in FIG. 4. The outer bundle 26 will be
noted as providing a means for transmitting infrared light within the
designated spectral range to the point of light entry 20 so as to provide
photons capable of penetrating both the skin and bone layer as well as the
gray matter and white matter schematically illustrated in FIG. 3. Those
photons which are directly reflected upwardly from tissues below the light
entry assembly 25 or within a few millimeters of that point of entry are
transmitted through the inner optic bundle 27 to an appropriate reference
detector 35 whereas other photons are transmitted, reflected and scattered
through and by the skin and bone structure, through and by the gray matter
to and from the white matter to provide a continuous number of such
photons reaching the point of light exit 21 where they are picked up by
another single fiber optics bundle 40 and transmitted to a measuring
detector 41, with the output of reference detector 35 and measuring
detector 41 being directed to suitable processing circuitry 45 for
conversion to a signal indicative of oxygen sufficiency in the gray matter
as hereafter more fully described.
Since the types of light sources, reference detecting, measuring detecting
and processing circuitry have already been fully described in the prior
copending application Ser. No. 810,777, no attempt will be made here to
describe the circuitry in anymore detail since the same should be readily
apparent to those skilled in the art from the information already given.
What is of particular importance to the present invention is recognition of
the discovery that the spacing between the points of light entry and exit
20, 21 has a significant relation to the source of photons which are
picked up through the fiber optics bundle 40 and transferred to the
measuring detector 41. For example, it will be seen that when the distance
between the points of light entry and exit 20, 21 is less than
approximately 4.25 centimeters that the photons reaching the exit point 21
will consist of light principally made up of photons scattered by and in
the skin and bone. In contrast, it will be noted in reference to FIG. 2
that when the spacing between the points of light entry and exit 20, 21 is
greater than approximately 4.25 centimeters that the photons reaching the
fiber optics bundle assembly 40 will consist principally of light
scattered by and in the gray matter of the brain. Thus, by using the inner
fiber optic bundle 27 to receive light directly reflected and scattered
upwards, photons reflected from the skin and bone will predominate as
indicated in FIGS. 2 and 3 and using this as a reference to measuring
detector 41 in processing circuitry 45, a signal can be obtained which is
sufficiently accurate to represent oxygen sufficiency in the gray matter.
Further, the photons representing those which have been scattered and
reflected by the skin and bone and detected by reference detector 35 may
be used for signal stabilization against variations in light output of
source 22 and, importantly, for correction for skin blood volume changes.
In one embodiment of the invention, four legs of a five-legged fiber bundle
were employed as the fiber bundle 26 to bring light of four wavelengths
from the light source 22, comprising laser diodes, to the point of light
entry 20. In the same fiber optics assembly 25, the fifth fiber bundle leg
was employed to pick up the skin and bone reflectance in the area
immediately adjacent to the entry point 20 of the laser light from light
source 22. The same embodiment included appropriate subtraction circuitry
for correction of blood volume changes attributable to the skin and bone.
The sensors employed in reference detector 35 and measuring detector 41
were closely matched and associated with differential circuit means in the
processing circuitry 45. Thus, one sensor was employed for measuring the
light emanating from the head at the exit point 21 several centimeters
away from the entry point 20. The second sensor 35 was employed for
sensing the light reflectedbelow the point of entry 20 and utilizing the
appropriate processing circuitry 45 provided a useful signal indicative of
oxygen sufficiency in the gray matter and corrected for changes in skin
and bone blood volume. Further, the light from light source 22 was
presented at measuring and contrabestic reference wavelengths alternately
at a rate sufficiently rapid to provide a sufficiently short reference and
measuring cycle such that the metabolic and circulatory parameters were
treated as being essentially constant within the time period of each
measuring cycle.
Data from actual experiments utilizing the present invention are
illustrated in reference to FIGS. 5, 6 and 6A with FIG. 6A being a
continuation of FIG. 6. The interpretation of these figures will be
readily understood using the disclosure of the prior copending application
Ser. No. 810,777 as background. In particular, FIG. 5 illustrates that
hyperventilation, as in the prior invention, produces in the present
invention the e | | |
