Pathlength corrected oximeter and the like

• US 5,564,417 A
• Filed: 03/16/1993
• Issued: 10/15/1996
• Est. Priority Date: 01/24/1991
• Status: Expired due to Term

• Current Assignee: Nim Incorporated
• Original Assignee: Non-Invasive Technology Incorporated
• Inventors: Chance, Britton
• Primary Examiner(s): Shay, David M.
• Application Number:
  US08/031,945
• Time in Patent Office: 1,309 Days
• Field of Search: 606/2, 606/10-12, 128/633, 128/634, 128/664, 128/665, 128/897, 128/898, 356/4, 356/5, 356/51, 356/39, 356/72, 356/319, 356/320, 356/323, 356/341, 356/432-436, 356/256
• US Class Current: 600/476
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/043 in a linear array
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6828 Leg
• CPC Class Codes: G01N 2021/1789 Time resolved
• CPC Class Codes: G01N 2021/3181 using LEDs
• CPC Class Codes: G01N 21/3151 using two sources of radiation of different wavelengths G01N21/33 - G01N21/39 take precedence
• CPC Class Codes: G01N 21/47 Scattering, i.e. diffuse reflection G01N21/25, G01N21/41 take precedence G01N21/55 takes precedence
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2201/0696 Pulsed

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.

Claims

1. A spectrophotometer for biological tissue examination, comprising:

a support structure adapted to be mounted on a subject including

an optical input port located at a first location to introduce light to biological tissue of the subject;

an optical detection port located at a second location on said support structure spaced apart from said input port; and

a barrier constructed and positioned to absorb photons directly propagating from said input port to said detection port;

an oscillator, including oscillator electronics, that generates a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from said optical input port to said optical detection port, said frequency being above 10 MHz;

a light source mounted on said support structure and connected to and receiving said carrier waveform from said oscillator, said light source generates light of a selected wavelength that is intensity modulated at said frequency and is introduced to the tissue of the subject at said input port;

a photodiode detector mounted on said support structure and connected to said detection port, said photodiode detector detects scattered light of said wavelength that has migrated in examined tissue of the subject between said input and detection ports;

a phase detector, including phase detector electronics, connected to receive signals from said oscillator and said diode detector, said phase detector measures a phase shift between said introduced light and said detected light that has migrated in the examined tissue over photon migration paths from said input port to said detection port; and

a processor connected to receive said phase shift from said phase detector, said processor determines, based on said measured phase shift, a physiological property of the examined tissue dependent on tissue scattering and absorptive properties.

5. The spectrophotometer of claim 1 or 4 further comprising:

a magnitude detector, including magnitude detector electronics, connected to said photodiode detector, said magnitude detector measures magnitude of said detected light, and

two automatic gain controls connected to receive signals corresponding to said introduced light and said detected light, respectively, and level both said signals, both said leveled signals being introduced to said phase detector.

6. The spectrophotometer of claim 1 or 4 further comprising two automatic gain controls, including automatic gain control electronics, connected to receive signals corresponding to said introduced light and said detected light, respectively, and level both said signals, both said leveled signals being introduced to said phase detector.

7. The spectrophotometer of claim 1 or 4 further comprising:

said support structure further including

a second optical input port located at a second location and constructed to introduce light to the tissue; and

a second optical detection port located on said support structure spaced apart from said input ports;

a second light source, mounted on said support structure and connected to and receiving from said oscillator said carrier waveform, said second light source generates light of a second selected wavelength that is intensity modulated at said first frequency and is introduced to the tissue of the subject at said second input port;

a second photodiode detector mounted on said support structure and connected to said second detection port, said second photodiode detector detects light of said second wavelength that has migrated in the tissue of the subject between said second input port and said second detection port, respectively;

a second phase detector, including phase detector electronics, connected to receive a reference signal and a detection signal from said second photodiode detector and measure a phase shift between said introduced and said detected light at said second wavelength; and

said processor further connected to receive from said second phase detector a second phase shift at said second wavelength, said first and second phase shifts being subsequently used for determination of said physiological property.

8. The spectrophotometer of claim 7 further comprising:

a first and a second magnitude detector, including corresponding magnitude detector electronics, connected to said first and second photodiode detectors, respectively, said magnitude detectors measure magnitude of said detected light at each of said wavelengths, and

said processor further connected to receive from said first and said second magnitude detector said magnitudes for determination of said physiological property.

9. The spectrophotometer of claim 7 further comprising:

said support structure further including

a third optical input port located at a third location and constructed to introduce light to the tissue; and

a third optical detection port located on said support structure spaced apart from said input ports;

a third light source mounted on said support structure and connected to said oscillator, said third light source generates light of a third selected wavelength that is intensity modulated at said first frequency and is introduced to the tissue of the subject at said third input port;

a third photodiode detector mounted on said support structure and connected to said third detection port, light of said third wavelength that has migrated in the tissue of the subject between said third input port and said third detection port, respectively;

a third phase detector, including phase detector electronics, connected to receive a reference signal and a detection signal from said third photodiode detector, said third phase detector measures a phase shift between said introduced and said detected light at said third wavelength; and

said processor further connected to receive phase shift at said third wavelength from said third phase detector, said first, second and third wavelength phase shifts being subsequently used for determination of said physiological property.

10. The spectrophotometer of claim 9 wherein each said photodiode detector is a PIN diode.

11. The spectrophotometer of claim 9 wherein each said photodiode detector is an avalanche diode.

12. The spectrophotometer of claim 9 further comprising:

a first, a second and a third magnitude detector, including corresponding magnitude detector electronics, connected to said first, second and third photodiode detectors, respectively, said magnitude detectors measure magnitude of said detected light at each of said wavelengths; and

said processor further connected to receive said magnitudes for determination of said physiological property.

13. The spectrophotometer of claim 9 wherein each said light source is a light emitting diode and said selected wavelength is in the visible or infra-red range.

14. The spectrophotometer of claim 9 wherein each said photodiode detector further comprises a substantially single wavelength filter.

15. The spectrophotometer of claim 1, 2 or 4 further comprising:

a low frequency oximeter, including a corresponding circuit, removably connected to said source and said photodiode, said low frequency oximeter controls introduction of low frequency modulated light at said wavelength, and detection of light that has migrated from said input port to said detection port in the examined tissue

said processor removably connected to said low frequency oximeter and further constructed to receive absorption values from said oximeter for determination of said physiological property.

16. The spectrophotometer of claim 15 wherein said processor is programmed to calculate, based on said measured phase shift, an average pathlength of photons migrating from said input port to said detection port in the examined tissue and utilize said pathlength for calibrating said absorption values from said low frequency oximeter.

17. The spectrophotometer of claim 1, 2 or 4 further comprising:

a magnitude detector, including magnitude detector electronics, connected to said photodiode detector, said magnitude detector measures magnitude of said detected light, and

said processor further connected to and receiving from said magnitude detector magnitude data for determination of said physiological property.

18. The spectrophotometer of claims 1, 2 or 4 wherein said light source is a light emitting diode and said selected wavelength is in the visible or infra-red range.

19. The spectrophotometer of claims 1, 2 or 4 wherein said photodiode detector is a PIN diode.

20. The spectrophotometer of claims 1, 2 or 4 wherein said photodiode detector is an avalanche diode.

21. The spectrophotometer of claims 1, 2 or 4 wherein said photodiode detector further comprises a substantially single wavelength filter.

22. The spectrophotometer of claim 1, 2 or 4 further comprising:

a second optical input port coupled to said support structure located at a second location and constructed to introduce light to the examined tissue;

a second light source mounted on said support structure and connected to said oscillator, said second light source generates light of a second selected wavelength that is intensity modulated at said first frequency and is introduced to the tissue of the subject at said second input port;

said photodiode detector including a second photodiode that further detects alternately, at said detection port, light of said first and second wavelengths that have migrated in the tissue of the subject between the first and said second input ports and said detection port, respectively;

said phase detector further receives alternately from said diode detector signals corresponding to said detected light of said first and second wavelengths; and

said processor further receives alternately phase shifts at said first and second wavelengths from said phase detector, said phase shifts being subsequently used for determination of said physiological property.

23. The spectrophotometer of claim 22 further comprising:

a magnitude detector, including magnitude detector electronics, connected to said photodiode detector, said magnitude detector measures magnitude of said detected light at each of said wavelengths, and

said processor further connected to and receiving from said magnitude detector said magnitudes for determination of said physiological property.

24. The spectrophotometer of claim 1, 2 or 4 further comprising a readout device, worn by said subject, for displaying data of said processor related to said physiological property.

25. The spectrophotometer of claim 1, 2 or 4 further comprising a telemetry apparatus for sending acquired data to a remote location.

26. The spectrophotometer of claim 1, 2 or 4 wherein said frequency of said oscillator is about 50.1 MHz.

27. The spectrophotometer of claim 1, 2 or 4 wherein said oscillator is constructed to maintain long term stability of operation.

28. The spectrophotometer of claim 1, 2 or 4 wherein said physiological property of the examined tissue is related to levels of one of the following:

myoglobin, hemoglobin oxygenation, cytochrome iron, cytochrome copper, melanin and glucose in the examined tissue.

29. The spectrophotometer of claim 1, 2 or 4 wherein said physiological property is a scattering coefficient (μ

_s) of the examined tissue.

30. The spectrophotometer of claim 1, 2 or 4 wherein said physiological property is an absorption coefficient (μ

_a) of the examined tissue.

2. A spectrophotometer for biological tissue examination, comprising:

a support structure adapted to be mounted on a subject including

an optical input port located at a first location to introduce light to biological tissue of the subject;

an optical detection port located at a second location on said support structure spaced apart from said input port; and

a barrier constructed and positioned to absorb photons directly propagating from said input port to said detection port;

an oscillator, including oscillator electronics, that generates a carrier waveform of a selected frequency comparable to an average migration time of photons scattered in tissue on paths from said optical input port to said optical detection port, said frequency being above 10 MHz;

a light source mounted on said support structure and connected to and receiving said carrier waveform from said oscillator, said light source generates light of a selected wavelength that is intensity modulated at said frequency and is introduced to the tissue of the subject at said input port;

a photodiode detector, mounted on said support structure and connected to said detection port, said photodiode detector detects scattered light of said wavelength that has migrated in examined tissue of the subject between said input and detection ports and produces a detector signal;

a phase splitter, including a phase splitter circuit, that receives said carrier waveform and produces, first and second reference phase signals of predefined substantially different phases;

first and second double balanced mixers, including corresponding mixer circuits, that receive and correlate said reference phase signals and said detector signals to produce therefrom a real output signal and an imaginary output signal, respectively;

a processor connected to receive from said mixers said real output signal and said imaginary output signal, said processor determines from real output signal and an imaginary output signal a phase shift between said introduced light and said detected light; and

said processor further determines, based on said phase shift, a physiological property of the examined tissue dependant on tissue scattering or absorptive properties.

3. The spectrophotometer of claim 2 wherein phase difference between said first reference phase signal and said second reference phase signal is 90 degrees.

4. A spectrophotometer for biological tissue examination, comprising:

a support structure adapted to be mounted on a subject including

an optical input port located at a first location to introduce light to biological tissue of the subject;

an optical detection port located at a second location on said support structure spaced apart from said input port; and

a barrier constructed and positioned to absorb photons directly propagating from said input port to said detection port;

a first oscillator, including oscillator electronics, that generates a carrier waveform of a first selected frequency comparable to an average migration time of photons scattered in tissue on paths from said optical input port to said optical detection port, said frequency being above 10 MHz;

a light source mounted on said support structure and connected to and receiving said carrier waveform from said oscillator, said light source generates light of a selected wavelength that is intensity modulated at said first frequency and is introduced to the tissue of the subject at said input port;

a photodiode detector mounted on said support structure and connected to said detection port, said photodiode detector detects light of said wavelength that has migrated in examined tissue of the subject between said input and detection ports and produces a detection signal at said first frequency corresponding to said detected light;

a second oscillator, including oscillator electronics, that generates a carrier waveform of a second frequency;

a reference mixer, including mixer electronics, connected to said first and second oscillators, said reference mixer generates a reference signal of a frequency approximately equal to the difference between said first and second frequencies;

a mixer, including mixer electronics, connected to receive signals from said second oscillator and said detection signal, said mixer converts said detection signal to a converted detection signal at said difference frequency;

a phase detector, including phase detector electronics, connected to receive reference signals from said reference mixer and said converted detection signal from said mixer, said phase detector measures a phase shift between said introduced light and said detected light that has migrated in the examined tissue over photon migration paths from said input port to said detection port; and

a processor connected to receive phase shift signal from said phase detector, said processor determines, based on said measured phase shift, a physiological property of the examined tissue dependent on tissue scattering or absorptive properties.