U.S. patent application number 10/174482 was filed with the patent office on 2003-01-30 for pathlength corrected oximeter and the like.
Invention is credited to Chance, Britton.
Application Number | 20030023140 10/174482 |
Document ID | / |
Family ID | 23154125 |
Filed Date | 2003-01-30 |
United States Patent
Application |
20030023140 |
Kind Code |
A1 |
Chance, Britton |
January 30, 2003 |
Pathlength corrected oximeter and the like
Abstract
A pathlength corrected spectrophotometer for tissue examination
includes an oscillator for generating a carrier waveform of a
selected frequency, an LED light source for generating light of a
selected wavelength that is intensity modulated at the selected
frequency introduced to a subject, and a photodiode detector for
detecting light that has migrated in the tissue of the subject. The
spectrophotometer also includes a phase detector for measuring a
phase shift between the introduced and detected light, a magnitude
detector for determination of light attenuation in the examined
tissue, and a processor adapted to calculate the photon migration
pathlength and determine a physiological property of the examined
tissue based on the pathlength and on the attenuation data.
Inventors: |
Chance, Britton; (Marathon,
FL) |
Correspondence
Address: |
JOHN N. WILLIAMS
Fish & Richardson P.C.
225 Franklin Street
Boston
MA
02110-2804
US
|
Family ID: |
23154125 |
Appl. No.: |
10/174482 |
Filed: |
June 18, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10174482 |
Jun 18, 2002 |
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09299284 |
Apr 26, 1999 |
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6183414 |
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09299284 |
Apr 26, 1999 |
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08731443 |
Oct 15, 1996 |
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6134460 |
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08731443 |
Oct 15, 1996 |
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08031945 |
Mar 16, 1993 |
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5564417 |
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08031945 |
Mar 16, 1993 |
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08076370 |
Jun 14, 1993 |
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5553614 |
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08076370 |
Jun 14, 1993 |
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07645590 |
Jan 24, 1991 |
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07645590 |
Jan 24, 1991 |
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07578063 |
Sep 5, 1990 |
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5122974 |
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07578063 |
Sep 5, 1990 |
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07307066 |
Feb 6, 1989 |
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4972331 |
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Current U.S.
Class: |
600/38 |
Current CPC
Class: |
A61F 5/41 20130101; G01N
2021/3181 20130101; A61B 2562/043 20130101; A61B 5/14551 20130101;
A61F 2005/411 20130101; A61B 2562/0233 20130101; G01N 2021/1791
20130101; A61B 5/14553 20130101; G01N 21/47 20130101; G01N
2201/0696 20130101; G01J 9/04 20130101; G01N 21/4795 20130101; G01N
21/3151 20130101; G01N 2021/1789 20130101; G01N 21/49 20130101;
A61B 2562/0242 20130101; G01N 2201/06113 20130101 |
Class at
Publication: |
600/38 |
International
Class: |
A61F 005/00 |
Claims
1. A spectrophotometer for tissue examination utilizing a measured
average pathlength of migrating photons, comprising: an oscillator
adapted to generate a carrier waveform of a selected frequency
comparable to an average migration time of photons scattered in
tissue on paths from an optical input port to an optical detection
port; a light source, operatively connected to said oscillator,
adapted to generate light of a selected wavelength that is
intensity modulated at said frequency, said light being introduced
to a subject at said input port; a photodiode detector adapted to
detect, at said detection port, light of said wavelength that has
migrated in said tissue of the subject between said input and
detection ports; a phase detector, operatively connected to receive
signals from said oscillator and said diode detector, adapted to
measure a phase shift between said introduced and said detected
light; a processor adapted to determine said pathlength based on
said phase shift; and said processor further adapted to determine a
physiological property of the examined tissue based on said
pathlength.
2. A spectrophotometer for tissue examination utilizing a measured
average pathlength of migrating photons, comprising: an oscillator
adapted to generate a carrier waveform of a selected frequency
comparable to an average migration time of photons scattered in
tissue on paths from an optical input port to an optical detection
port; a light source, operatively connected to said oscillator,
adapted to generate light of a selected wavelength that is
intensity modulated at said frequency, said light being introduced
to a subject at said input port; a photodiode detector adapted to
detect, at said detection port, light of said wavelength that has
migrated in said tissue of the subject between said input and
detection ports; a phase splitter adapted to produce, based on said
carrier waveform, first and second reference phase signals of
predefined substantially different phase; first and second double
balanced mixers adapted to correlate said reference phase signals
and signals of said detected radiation to produce therefrom a real
output signal and an imaginary output signal, respectively; a
processor adapted to determine, on the basis of said real output
signal and said imaginary output signal, a phase shift between said
introduced light and said detected light; and said processor
further adapted to determine a physiological property of the
examined tissue based on said phase shift.
3. A spectrophotometer for tissue examination utilizing a measured
average pathlength of migrating photons, comprising: a first
oscillator adapted to generate a carrier waveform of a first
selected frequency comparable to an average migration time of
photons scattered in tissue on paths from an optical input port to
an optical detection port; a light source, operatively connected to
said oscillator, adapted to generate light of a selected wavelength
that is intensity modulated at said first frequency, said light
being introduced to a subject at said input port; a photodiode
detector adapted to detect, at said detection port, light of said
wavelength that has migrated in said tissue of the subject between
said input and detection ports, said detector producing a detection
signal at said first frequency corresponding to said detected
light; a second oscillator adapted to generate a carrier waveform
of a second frequency that is offset on the order of 10.sup.4 Hz
from said first frequency; a reference mixer, connected to said
first and second oscillators, adapted to generate a reference
signal of a frequency approximately equal to the difference between
said first and second frequencies; a mixer connected to receive
signals from said second oscillator and said detection signal and
adapted to convert said detection signal to said difference
frequency; a phase detector, operatively connected to receive
signals from said reference mixer and said converted detection
signal, adapted to measure a phase shift between said introduced
light and said detected light, a processor adapted to determine
said pathlength based on said phase shift; and said processor
further adapted to determine a physiological property of the
examined tissue based on said pathlength.
4. The spectrophotometer of claims 1, 2 or 3 further comprising: a
magnitude detector, connected to said photodiode detector, adapted
to measure magnitude of said detected light, and said processor
further adapted to receive said magnitude for determination of said
physiological property.
5. The spectrophotometer of claims 1, 2 or 3 further comprising: a
low frequency oximeter circuit, switchably connected to said source
and said photodiode, adapted to determine absorption of light at
said wavelength; and said processor further adapted to receive
absorption values from said oximeter circuit for determination of
said physiological property.
6. The spectrophotometer of claims 1 or 3 further comprising two
automatic gain controls adapted to level signals corresponding to
said introduced light and said detected light, both said leveled
signals being introduced to said phase detector.
7. The spectrophotometer of claims 1 or 3 further comprising: a
magnitude detector, connected to said photodiode detector, adapted
to measure magnitude of said detected light, and two automatic gain
controls adapted to level signals corresponding to said introduced
light and said detected light, both said leveled signals being
introduced to said phase detector.
8. The spectrophotometer of claims 1, 2 or 3 wherein said light
source is a light emitting diode and said selected wavelength is in
the visible or infra-red range.
9. The spectrophotometer of claims 1, 2 or 3 wherein said
photodiode detector is a PIN diode.
10. The spectrophotometer of claims 1, 2 or 3 wherein said
photodiode detector is an avalanche diode.
11. The spectrophotometer of claims 1, 2 or 3 wherein said
photodiode detector further comprises a substantially single
wavelength filter.
12. The spectrophotometer of claims 1, 2 or 3 further comprising: a
second light source, operatively connected to said oscillator,
adapted to generate light of a second selected wavelength that is
intensity modulated at said first frequency, said radiation being
introduced to a subject at a second input port; said photodiode
detector further adapted to detect alternately, at said detection
port, light of said first and second wavelengths that have migrated
in said tissue of the subject between the first and said second
input ports and said detection port, respectively; said phase
detector further adapted to receive alternately signals
corresponding to said detected first and second wavelengths; and
said processor further adapted to receive alternately phase shifts
from said phase detector, said phase shifts being subsequently used
for determination of said physiological property.
13. The spectrophotometer of claim 12 further comprising: a
magnitude detector, connected to said photodiode detector, adapted
to measure magnitude of said detected light at each of said
wavelengths, and said processor further adapted to receive said
magnitudes for determination of said physiological property.
14. The spectrophotometer of claims 1 or 3 further comprising: a
second light source, operatively connected to said oscillator,
adapted to generate light of a second selected wavelength that is
intensity modulated at said first frequency, said radiation being
introduced to a subject at a second input port; a second photodiode
detector adapted to detect, at a second detection port, light of
said second wavelength that has migrated in said tissue of the
subject between said second input port and said second detection
port, respectively; a second phase detector, operatively connected
to receive a reference signal and a detection signal from said
third diode detector, adapted to measure a phase shift between said
introduced and said detected light at said second wavelength; and
said processor further adapted to receive a second phase shift at
said second wavelength, said first and second phase shifts being
subsequently used for determination of said physiological
property.
15. The spectrophotometer of claim 14 further comprising: a first
and a second magnitude detector connected to said first and second
photodiode detectors, respectively, said magnitude detectors being
adapted to measure magnitude of said detected light at each of said
wavelengths, and said processor further adapted to receive said
magnitudes for determination of said physiological property.
16. The spectrophotometer of claims 14 further comprising: a third
light source, operatively connected to said oscillator, adapted to
generate light of a third selected wavelength that is intensity
modulated at said first frequency, said radiation being introduced
to a subject at a third input port; a third photodiode detector
adapted to detect, at a third detection port, light of said third
wavelength that has migrated in said tissue of the subject between
said third input port and said third detection port, respectively;
a third phase detector, operatively connected to receive a
reference signal and a detection signal from said third diode
detector, adapted to measure a phase shift between said introduced
and said detected light at said third wavelength; and said
processor further adapted to receive phase shifts from said phase
detector, said first second and third phase shifts being
subsequently used for determination of said physiological
property.
17. The spectrophotometer of claim 14 further comprising: a first,
a second and a third magnitude detector connected to said first,
second and third photodiode detectors, respectively, said magnitude
detectors being adapted to measure magnitude of said detected light
at each of said wavelengths; and said processor further adapted to
receive said magnitudes for determination of said physiological
property.
18. The spectrophotometer of claim 16 wherein each said light
source is a light emitting diode and said selected wavelength is in
the visible or infra-red range.
19. The spectrophotometer of claim 16 wherein each said photodiode
detector is a PIN diode.
20. The spectrophotometer of claim 16 wherein each said photodiode
detector is an avalanche diode.
21. The spectrophotometer of claim 16 wherein each said photodiode
detector further comprises a substantially single wavelength
filter.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of application
Ser. No. 07/645,590 filed Jan. 24, 1991 incorporated by reference
as if fully set forth herein.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to a wearable tissue
spectrophotometer for in vivo examination of tissue of a specific
target region.
[0003] Continuous wave (CW) tissue oximeters have been widely used
to determine in vivo concentration of an optically absorbing
pigment (e.g., hemoglobin, oxyhemoglobin) in biological tissue. The
CW oximeters measure attenuation of continuous light in the tissue
and evaluate the concentration based on the Beer Lambert equation
or modified Beer Lambert absorbance equation. The Beer Lambert
equation (1) describes the relationship between the concentration
of an absorbent constituent (C), the extinction coefficient
(.epsilon.), the photon migration pathlength <L>, and the
attenuated light intensity (I/I.sub.o). 1 log [ I / I 0 ] L = i C i
( 1 )
[0004] The CW spectrophotometric techniques can not determine
.epsilon., C, and <L> at the same time. If one could assume
that the photon pathlength were constant and uniform throughout all
subjects, direct quantitation of the constituent concentration (C)
using CW oximeters would be possible.
[0005] In tissue, the optical migration pathlength varies with the
size, structure, and physiology of the internal tissue examined by
the CW oximeters. For example, in the brain, the gray and white
matter and the structures thereof are different in various
individuals. In addition, the photon migration pathlength itself is
a function of the relative concentration of absorbing constituents.
As a result, the pathlength through an organ with a high blood
hemoglobin concentration, for example, will be different from the
same with a low blood hemoglobin concentration. Furthermore, the
pathlength is frequently dependent upon the wavelength of the light
since the absorption coefficient of many tissue constituents is
wavelength dependent. Thus, where possible, it is advantageous to
measure the pathlength directly when quantifying the hemoglobin
concentration in tissue.
SUMMARY OF THE INVENTION
[0006] In one aspect, the present invention is a pathlength
corrected oximeter that utilizes principles of continuous wave
spectroscopy and phase modulation spectroscopy. The oximeter is a
compact unit constructed to be worn by a subject on the body over
long periods of activity. The oximeter is also suitable for tissue
monitoring in critical care facilities, in operating rooms while
undergoing surgery or in trauma related situations.
[0007] The oximeter is mounted on a body-conformable support
structure placed on the skin. The support structure encapsulates
several light emitting diodes (LEDs) generating light of different
wavelengths introduced into the examined tissue and several
photodiode detectors with interference filters for wavelength
specific detection. Since both the LEDs and the photodiodes are
placed directly on the skin, there is no need to use optical
fibers. The distance between the LEDs and the diode detectors is
selected to examine a targeted tissue region. The support structure
also includes a conformable barrier, located between the LEDs and
the diode detectors, designed to reduce detection of light that
migrates subcutaneously from the source to the detector. The
support structure may further include means for preventing escape
of photons from the skin without being detected; the photon escape
preventing means are located around the LEDs and the photodiode
detectors.
[0008] The LEDs, the diode detectors, and the electronic control
circuitry of the oximeter are powered by a battery pack adapted to
be worn on the body or by the standard 50/60 Hz supply. The
electronic circuitry includes a processor for directing operation
of the sources, the detectors and for directing the data
acquisition and processing. The data may be displayed on a readout
device worn by the user, sent by telemetry to a remote location or
accumulated in a memory for later use.
[0009] The oximeter is adapted to measure the attenuation of light
migrating from the source to the detector and also to determine the
average migration pathlength. The migration pathlength and the
intensity attenuation data are then used for direct quantitation of
a tissue property.
[0010] In another aspect, the invention is a spectrophotometer for
tissue examination utilizing a measured average pathlength of
migrating photons, including
[0011] an oscillator adapted to generate a carrier waveform of a
selected frequency comparable to an average migration time of
photons scattered in tissue on paths from an optical input port to
an optical detection port; a light source, operatively connected to
the oscillator, adapted to generate light of a selected wavelength
that is intensity modulated at the frequency and introduced to a
subject at the input port; a photodiode detector adapted to detect,
at the detection port, light of the selected wavelength that has
migrated in the tissue of the subject between the input and
detection ports; a phase detector, operatively connected to receive
signals from the oscillator and the diode detector, adapted to
measure a phase shift between the introduced and the detected
light; and a processor adapted to calculate pathlength based on the
phase shift, and determine a physiological property of the examined
tissue based on the pathlength.
[0012] In another aspect, the invention is a spectrophotometer for
tissue examination utilizing a measured average pathlength of
migrating photons, including an oscillator adapted to generate a
carrier waveform of a selected frequency comparable to an average
migration time of photons scattered in tissue on paths from an
optical input port to an optical detection port; a light source,
operatively connected to the oscillator, adapted to generate light
of a selected wavelength that is intensity modulated at the
frequency and introduced to a subject at the input port; a
photodiode detector adapted to detect, at the detection port, light
of the selected wavelength that has migrated in the tissue of the
subject between the input and detection ports; a phase splitter
adapted to produce, based on the carrier waveform, first and second
reference phase signals of predefined substantially different
phase; first and second double balanced mixers adapted to correlate
the reference phase signals and signals of the detected radiation
to produce therefrom a real output signal and an imaginary output
signal, respectively; and a processor adapted to calculate, on the
basis of the real output signal and the imaginary output signal, a
phase shift between the introduced light and the detected light,
and determine a physiological property of the examined tissue based
on the phase shift.
[0013] In another aspect, the invention is a spectrophotometer for
tissue examination utilizing a measured average pathlength of
migrating photons, comprising a first oscillator adapted to
generate a carrier waveform of a first selected frequency
comparable to an average migration time of photons scattered in
tissue on paths from an optical input port to an optical detection
port; a light source, operatively connected to the oscillator,
adapted to generate light of a selected wavelength, intensity
modulated at the first frequency, that is introduced to a subject
at the input port; a photodiode detector adapted to detect, at the
detection port, light of the wavelength that has migrated in the
tissue of the subject between the input and detection ports, the
detector producing a detection signal at the first frequency
corresponding to the detected light; a second oscillator adapted to
generate a carrier waveform of a second frequency that is offset on
the order of 10.sup.4 Hz from the first frequency; a reference
mixer, connected to the first and second oscillators, adapted to
generate a reference signal of a frequency approximately equal to
the difference between the first and second frequencies; a mixer
connected to receive signals from the second oscillator and the
detection signal and adapted to convert the detection signal to the
difference frequency; a phase detector, operatively connected to
receive signals from the reference mixer and the converted
detection signal, adapted to measure a phase shift between the
introduced light and the detected light; and a processor adapted to
calculate the pathlength based on the phase shift, and to determine
a physiological property of the examined tissue based on the
pathlength.
[0014] Preferred embodiments of these aspects may include one or
more of the following features.
[0015] The spectrophotometer may further include a magnitude
detector, connected to the photodiode detector, adapted to measure
magnitude of the detected light, and the processor is further
adapted to receive the magnitude for determination of the
physiological property.
[0016] The spectrophotometer may further include a low frequency
oximeter circuit, switchably connected to the source and the
photodiode, adapted to determine absorption of light at the
wavelength; and the processor is further adapted to receive
absorption values from the oximeter circuit for determination of
the physiological property.
[0017] The spectrophotometer may further include two automatic gain
controls adapted to level signals corresponding to the introduced
light and the detected light, both the leveled signals being
introduced to the phase detector.
[0018] The photodiode detector may further include a substantially
single wavelength filter.
[0019] The spectrophotometer may further include a second light
source, operatively connected to the oscillator, adapted to
generate light of a second selected wavelength that is intensity
modulated at the first frequency, the radiation being introduced to
a subject at a second input port; the photodiode detector further
adapted to detect alternately, at the detection port, light of the
first and second wavelengths that have migrated in the tissue of
the subject between the first and the second input ports and the
detection port, respectively; the phase detector further adapted to
receive alternately signals corresponding to the detected first and
second wavelengths; and the processor further adapted to receive
alternately phase shifts from the phase detector, the phase shifts
being subsequently used for determination of the physiological
property of the tissue.
[0020] The spectrophotometer may further include a second light
source, operatively connected to the oscillator, adapted to
generate light of a second selected wavelength that is intensity
modulated at the first frequency, the radiation being introduced to
a subject at a second input port; a second photodiode detector
adapted to detect, at a second detection port, light of the second
wavelength that has migrated in the tissue of the subject between
the second input port and the second detection port, respectively;
a second phase detector, operatively connected to receive a
reference signal and a detection signal from the third diode
detector, adapted to measure a phase shift between the introduced
and the detected light at the second wavelength; and the processor
further adapted to receive a second phase shift at the second
wavelength, the first and second phase shifts being subsequently
used for determination of the physiological property of the
tissue.
[0021] The two wavelength spectrophotometer may further include a
third light source, operatively connected to the oscillator,
adapted to generate light of a third selected wavelength that is
intensity modulated at the first frequency, the radiation being
introduced to a subject at a third input port; a third photodiode
detector adapted to detect, at a third detection port, light of the
third wavelength that has migrated in the tissue of the subject
between the third input port and the third detection port,
respectively; a third phase detector, operatively connected to
receive a reference signal and a detection signal from the third
diode detector, adapted to measure a phase shift between the
introduced and the detected light at the third wavelength; and the
processor further adapted to receive phase shifts from the phase
detector, the first second and third phase shifts being
subsequently used for determination of the physiological property
of the tissue.
[0022] The two or three wavelength spectrophotometer may further
include a first, a second (or a third) magnitude detector connected
to the first, second (or third) photodiode detectors, respectively,
the magnitude detectors being adapted to measure magnitude of the
detected light at each of the wavelengths; and the processor
further adapted to receive the magnitudes for determination of the
physiological property of the tissue.
[0023] The light source may be a light emitting diode for
generating light of a selected wavelength in the visible or
infra-red range.
[0024] The photodiode detector may be a PIN diode or an avalanche
diode.
[0025] The examined physiological property of the tissue may be
hemoglobin oxygenation, myoglobin, cytochrome iron and copper,
melanin, glucose or other.
BRIEF DESCRIPTION OF THE DRAWING
[0026] FIG. 1 is a block diagram of a pathlength corrected oximeter
in accordance with the present invention.
[0027] FIG. 2 is a schematic circuit diagram of a 50.1 MHz (50.125
MHz) oscillator used in the oximeter of FIG. 1.
[0028] FIG. 3 is a schematic circuit diagram of a PIN diode and a
preamplifier used in the oximeter of FIG. 1.
[0029] FIG. 4 is a schematic circuit diagram of a magnitude
detector used in the oximeter of FIG. 1.
[0030] FIG. 5 is a schematic circuit diagram of a 25 kHz filter
used in the oximeter of FIG. 1.
[0031] FIG. 6 is a schematic diagram of an AGC circuit of the
oximeter of FIG. 1.
[0032] FIG. 7 is a schematic circuit diagram of a phase detector of
the oximeter of FIG. 1.
[0033] FIG. 8A is a plan view of a source-detector probe of the
oximeter.
[0034] FIG. 8B is a transverse cross-sectional view taken on lines
8B of FIG. 8A further showing the photon migration.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0035] One preferred embodiment of the pathlength corrected
oximeter utilizes three LEDs for generation of light at three
selected wavelengths intensity modulated at a frequency of 50.1 MHz
and coupled directly to the examined tissue. At each wavelength,
the introduced light is altered by the tissue and is detected by a
wide area photodiode placed against the skin. The introduced and
detected radiations are compared to determine their relative phase
shift that corresponds to an average pathlength of the migrating
photons and, furthermore, the light attenuation is determined.
[0036] Referring to FIG. 1, the oximeter includes a master
oscillator 10 operating at 50.1 MHz connected to a power amplifier
15 of sufficient output power to drive LEDs 22a, 22b, and 22c (for
example HLP 20RG or HLP 40RG made by Hitachi) that emit 760 nm, 840
nm, and 905 nm (or 950 nm) light, respectively. A second local
oscillator 14 operating at 50.125 MHz and mixer 12 are used to
generate a reference frequency 13 of 25 kHz. Each LED directly
positioned on the skin has an appropriate heat sink to eliminate
uncomfortable temperature increases that could also alter blood
perfusion of the surrounding tissue. Three PIN diode detectors 24a,
24b, and 24c are placed at a distance of approximately 5 cm from
the LEDs and have a detection area of about 1 cm.sup.2. Photons
migrating a few centimeters deep into the tissue are detected by
the respective PIN diodes. The source-detector separation can be
increased or decreased to capture deeper or shallower migrating
photons. The signals from PIN diodes 24a, 24b, and 24c are
amplified by preamplifiers 30a, 30b, and 30c, respectively.
[0037] The amplified signals (32a, 32b, 32c) are sent to magnitude
detectors 36a, 36b, and 36c and to mixers 40a, 40b, and 40c,
respectively. The magnitude detectors are used to determine
intensity values of detected signals at each wavelength to be used
in Eq. 1. Each mixer, connected to receive a 50.125 MHz reference
signal (41a, 41b, 41c) from local oscillator 14, converts the
detection signal to a 25 kHz frequency signal (42a, 42b, 42c). The
mixers are high dynamic range frequency mixers, model SRA-1H,
commercially available from Mini-Circuits (Brooklyn N.Y.). The
detection signals (42a, 42b, and 42c) are filtered by filters 45a,
45b, 45c, respectively.
[0038] Phase detectors 60a, 60b, and 60c are used to determine
phase shift between the input signal and the detected signal at
each wavelength. Each phase detector receives the 25 kHz detection
signal (54a, 54b, 54c) and the 25 kHz reference signal (56a, 56b,
56c), both of which are automatically leveled by automatic gain
controls 50 and 52 to cover the dynamic range of signal changes.
Phase detectors 60a, 60b, and 60c generate phase shift signals
(62a, 62b, 62c) corresponding to the migration delay of photons at
each wavelength. Each phase shift signal is proportional to the
migration pathlength used in calculation algorithms performed by
processor 70.
[0039] FIG. 2 shows a schematic circuit diagram of a precision
oscillator used as the 50.1 MHz master oscillator 10 and 50.125 MHz
local oscillator 14. The oscillator crystals are neutralized for
operation in the fundamental resonance mode; this achieves
long-term stability. Both oscillators are thermally coupled so that
their frequency difference is maintained constant at 25 kHz if a
frequency drift occurs.
[0040] PIN diodes 24a, 24b, and 24c are directly connected to their
respective preamplifiers 30a, 30b, and 30c, as shown in FIG. 3. The
oximeter uses PIN silicon photodiodes S1723-04 with 10 mm.times.10
mm sensitive area and spectral response in the range of 320 nm to
1060 nm. The detection signal is amplified by stages 29 and 31,
each providing about 20 dB amplification. The NE5205N operational
amplifier is powered at +8V to operate in a high gain regime. The
8V signal is supplied by a voltage regulator 33. The amplified
detection signals (32a, 32b, and 32c) are sent to magnitude
detectors 36a, 36b, and 36c, shown in FIG. 4. The magnitude values
(37a, 37b, and 37c) are sent to processor 70 that calculates the
light attenuation ratio or logarithm thereof as shown Eq. 1.
[0041] Also referring to FIG. 5, the AGC circuit uses MC 1350
integrated circuit for amplification that maintains the input
signal of phase detector 60 at substantially constant levels. The
amount of gain is selected to be equal for AGCs, 50 and 52. The
signal amplitude is controlled by a feedback network 53. The AGCs
provide a substantially constant amplitude of the detected and
reference signals to eliminate variations in the detected phase
shift due to cross talk between amplitude and phase changes in the
phase detector.
[0042] Referring to FIG. 6, each phase detector includes a Schmitt
trigger that converts the substantially sinusoidal detection signal
(54a, 54b, 54c) and reference signal (56a, 56b, 56c) to square
waves. The square waves are input to a detector that has
complementary MOS silicon-gate transistors. The phase shift signal
is sent to processor 70.
[0043] The oximeter is calibrated by measuring the phase shift for
a selected distance in a known medium, i.e., using a standard delay
unit, and by switching the length of a connector wire to change the
electrical delay between master oscillator 10 and local oscillator
14.
[0044] Referring to FIGS. 8A and 8B source-detector probe 20
includes several LEDs (22a, 22b, 22c) of selected wavelengths and
PIN photodiodes (24a, 24b, 24c) mounted in a body-conformable
support structure 21. Structure 21 also includes a photon escape
barrier 27 made of a material with selected scattering and
absorption properties (for example, styrofoam) designed to return
escaping photons back to the examined tissue. The support structure
further includes a second conformable barrier 28, located between
the LEDs and the diode detectors, designed to absorb photons
directly propagating from the source to the detector and thus
prevent detection of photons that migrate subcutaneously. Support
structure 21 also includes electronic circuitry 29 encapsulated by
an electronic shield 21a.
[0045] Each PIN diode is provided with an evaporated single
wavelength film filter (25a, 25b, 25c). The filters eliminate the
cross talk of different wavelength signals and allow continuous
operation of the three light sources, i.e., no time sharing is
needed.
[0046] The use of photodiode detectors has substantial advantages
when compared with the photomultiplier tube used in standard phase
modulation systems. The photodiodes are placed directly on the
skin, i.e., no optical fibers are needed. Furthermore, there is no
need to use a high voltage power supply that is necessary for the
photomultiplier tube. The photodiodes are much smaller and are easy
to place close to the skin. Advantages of the photomultiplier tube
are a huge multiplication gain and a possibility of direct mixing
at the photomultiplier; this cannot be achieved directly by a
photodiode. This invention envisions the use of several different
photodiodes such as PIN diode, avalanche diode, and other.
[0047] The processor uses algorithms that are based on equations
described by E. M. Sevick et al. in "Quantitation of Time- and
Frequency-Resolved Optical Spectra for the Determination of Tissue
Oxygenation" published in Analytical Biochemistry 195, 330 Apr. 15,
1991 which is incorporated by reference as if fully set forth
herein.
[0048] At each wavelength, the phase shift (.theta..sup..lambda.)
(62a, 62b, 62c) is used to calculate the pathlength as follows: 2 =
tan - 1 f ( t ) = tan - 1 2 f L c 2 f L c ( 2 )
[0049] wherein f is modulation frequency of the introduced light
which is in the range of 10 MHz to 100 MHz; t.sup..lambda. is the
photon migration delay time; c is the speed of photons in the
scattering medium; and L.sup..lambda. is the migration
pathlength.
[0050] Equation (2) is valid at low modulation frequencies, i.e.,
2.pi.f<<.mu..sub.a.multidot.c. The modulation frequency of 50
MHz was selected due to the frequency limitation of the LEDs and
photodiodes. However, for faster LEDs and photodiodes it may be
desirable to use higher modulation frequencies that increase the
phase shift. At high modulation frequencies, i.e.,
2.pi.f>>.mu..sub.a.multidot.c, the phase shift is no longer
proportional to the mean time of flight <t>. 3 = a ( 1 - g )
s f { 1 - a c 4 f } ( 3 )
[0051] wherein .rho. is the source-detector separation; (1-g)
.mu..sub.s is effective scattering coefficient; f is modulation
frequency and .mu..sub.a.sup..lambda. is absorption coefficient at
wavelength .lambda.. At two wavelength, the ratio of absorption
coefficients is determined as follows: 4 a 1 a 2 = 1 - 0 1 2 - 0 2
( 4 )
[0052] wherein .theta..sub.0.sup..lambda. represents background
scattering and absorption.
[0053] The wavelengths are in the visible and infra-red range and
are selected to have absorbance sensitive (or insensitive) to
various tissue components such as water, cytochrome iron and
copper, oxy- and deoxygenated forms of hemoglobin, myoglobin,
melanin, glucose and other.
[0054] For oxygenated and deoxygenated hemoblogin, the absorption
coefficient written in terms of Beer Lambert relationship is as
follows: 5 a 1 = H b 1 [ H b ] + H b O 1 [ H b O 2 ] + 1 ( 5 )
[0055] wherein .epsilon..sub.Hb.sup..lambda.1 and
.epsilon..sub.Hb0.sup..- lambda.1 are extinction coefficients for
hemoglobin and deoxyhemoglobin that can be stored in a look up
table; [Hb], [HbO.sub.2] are the tissue concentration of hemoglobin
and oxyhemoglobin, respectively; .alpha..sup..lambda.1 is
background absorbance. The hemoglobin saturation is conventionally
defined as follows: 6 Y = [ H b O 2 ] [ H b ] + [ H b O 2 ] ( 6
)
[0056] For a three wavelength measurement, the hemoglobin
saturation can be calculated using Eqs. (5) and (6) as follows: 7 Y
= a ( H b 3 - H b 2 ) - ( H b 1 - H b 2 ) [ ( H b O 2 1 - H b O 2 2
) - ( H b 1 - H b 2 ) ] - a [ ( H b O 2 3 - ( H b O 2 2 ) - ( H b 3
- H b 2 ) ] w h e r e a = a 1 - a 2 a 3 - a 2 ( 7 )
[0057] Thus, processor 70 determines Y based on Eq. (7) using Eq.
(2) to determine the average migration pathlength L that is then
used in Eq. (1) and to determine .mu..sub.a.sup..lambda. for each
wavelength .lambda..sub.1, .lambda..sub.2, .lambda..sub.3.
[0058] In another embodiment, the spectrophotometer's electronics
includes a low frequency module suitably and a high frequency
module switchably coupled to the same source-detector probe 20. The
low frequency module and the arrangement of the source-detector
probe are substantially similar to the hemoglobinometer described
in a copending U.S. patent application Ser. No. 701,127 filed May
16, 1991 which is incorporated by reference as if fully set forth
herein. The low frequency module corresponds to a standard oximeter
with modulation frequencies in the range of a few hertz to 10.sup.4
hertz and is adapted to provide intensity attenuation data at two
or three wavelengths. Then, the LEDs are switched to the high
frequency phase modulation unit, similar to the unit of FIG. 1,
which determines the average pathlength at each wavelength. The
attenuation and pathlength data are sent to processor 70 for
determination of a physiological property of the examined
tissue.
[0059] In another embodiment, the pathlength corrected oximeter
utilizes the same LED sources (22a, 22b, 22c) sinusoidally
modulated at a selected frequency comparable to the average
migration time of photons scattered in the examined tissue on paths
from the optical input port of the LED's to the optical detection
part of the photodiode detectors (24a, 24b, 24c), but the
electronic circuitry is different. The detector output is put
through two wide band double balance mixers (DBM) which are coupled
through a 90.degree. phase splitter so that real (R) and imaginary
(I) portions of the signal are obtained. The double balance mixers
preferably operate at the modulation frequency. The phase
(.theta..sup..lambda.) is the angle whose tangent is the imaginary
over the real part. 8 = tan - 1 I R ( 8 )
[0060] The amplitude is the square root of the sum of the squares
of these values, providing the phase shift has been taken out as
the residual phase shift .theta. set to zero.
A.sup..lambda.={square root}{square root over
((R.sup..lambda.).sup.2+(I.s- up..lambda.).sup.2)} (9)
[0061] This embodiment uses summing and dividing circuits to
calculate the modulation index, which is the quotient of the
amplitude over the amplitude plus the DC component obtained from a
narrow band detector. 9 M = A A + D C ( 10 )
[0062] The phase processor receives the phase shifts for the phase
and amplitude values for two or three wavelengths and calculates
the ratio of the phase shifts.
[0063] For each wavelength, the phase shift and the DC amplitude
are used to determine a selected tissue property, e.g., hemoglobin
oxygenation.
[0064] Additional embodiments are within the following claims:
* * * * *