Tissue chromophore measurement system

• US 5,879,294 A
• Filed: 06/28/1996
• Issued: 03/09/1999
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Hutchinson Technology Incorporated (TDK Corporation)
• Original Assignee: Hutchinson Technology Incorporated (TDK Corporation)
• Inventors: Anderson, David L., Myers, Dean E., Ortner, Joseph P., Houk, Galen D., Lewandowski, Mark S.
• Primary Examiner(s): Peffley, Michael
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/672,625
• Time in Patent Office: 984 Days
• Field of Search: 128/63.3, 128/664, 128/665, 128/666, 356/39, 356/40, 356/41, 600/310, 600/322, 600/323, 600/473, 600/476, 600/479
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: G01J 3/433 Modulation spectrometry; Derivative spectrometry
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427

Abstract

A measurement system and method for measuring a relative concentration of a first form of a chromophore having a first form and a second form. The method comprises irradiating a tissue sample with light at a plurality of wavelengths within a wavelength range within which the first and second forms of the chromophore provide an overlapping spectral response. A detector is provided that detects spectral data emitted from the tissue. Furthermore, the method comprises determining a first and a second 2d derivative spectrum value, at first and second wavelengths, respectively, within said wavelength range at which the first 2d derivative spectrum value varies with the relative concentration of the first form of the chromophore. A scaled, 2d derivative spectrum value is derived from the first and second 2d derivative spectrum values. A memory stores a correlation which provides the relative chromophore concentration as a function of the scaled, 2d derivative spectrum value. Finally, the relative concentration of the first form of the chromophore in the tissue sample is determined from the 2d derivative spectrum values and the correlation.

Claims

1. A measurement system for determining a relative concentration of a first form of a chromophore in a tissue sample, said chromophore comprising at least a first form and a second form, comprising:

(a) means for irradiating said tissue sample with light at a plurality of wavelengths within a wavelength range within which the first and second forms of the chromophore provide an overlapping spectral response, such that spectral data is emitted from said tissue;

(b) means for detecting the spectral data emitted from said tissue;

(c) means for determining a first 2d derivative spectrum value of the spectral data at a first wavelength within said wavelength range at which the first 2d derivative spectrum value varies with the relative concentration of the first form of the chromophore;

(d) means for determining a second 2d derivative spectrum value of the spectral data at a second wavelength within said wavelength range at which the first 2d derivative spectrum value varies with the relative concentration of the first form of the chromophore;

(e) means for deriving a scaled, 2d derivative spectrum value from information comprising the first and second 2d derivative spectrum values; and

(f) means for storing a correlation which provides the relative chromophore concentration as a function of the scaled, 2d derivative spectrum value; and

(g) means for determining the relative concentration of the first form of the chromophore in the tissue sample from information comprising the scaled, 2d derivative spectrum value and the correlation.

2. The measurement system of claim 1 wherein said means for irradiating said predetermined tissue with light comprises a continuous wave, broad bandwidth light source.

3. The measurement system of claim 2 wherein said means for irradiating said predetermined tissue with light further comprises a light transmission probe having at least one optical fiber for passing light emitted by said continuous wave, broad bandwidth light source to said predetermined tissue.

4. The measurement system of claim 3 wherein said light transmission probe is comprised of a nonfluorescing material.

5. The measurement system of claim 4 wherein said light transmission probe is further comprised of a spectrally flat material over a spectral region of interest.

6. The measurement system of claim 5 wherein at least one end of said at least one optical fiber is configured as a side-firing optical fiber.

7. The measurement system of claim 4 wherein the probe includes an opaque face.

8. The measurement system of claim 1 wherein said means for irradiating said predetermined tissue comprises an infra-red (IR) filter device to eliminate passage of IR radiation to said predetermined tissue.

9. The measurement system of claim 1 wherein said means for detecting the spectral data emitted from said predetermined tissue comprises a wavelength sensitive detector.

10. The measurement system of claim 9 wherein said wavelength sensitive signal detector comprises a linear diode array spectrometer.

11. The measurement system of claim 9 wherein said wavelength sensitive signal detector comprises a linear capacitor array spectrometer.

12. The measurement system of claim 9 wherein said means for detecting the spectral data emitted from said predetermined tissue further comprises a light receive probe having at least one optical fiber for passing said light emitted from said predetermined tissue to said signal detector.

13. The measurement system of claim 1 wherein said means for detecting the spectral data emitted from predetermined tissue comprises a high pass filtering device adapted to cut off passage of said light signals emitted from said predetermined tissue at wavelengths below approximately 500 nanometers.

14. The measurement system of claim 1 wherein said means for storing said correlation is a computer memory.

15. The measurement system of claim 1 wherein said means for determining said relative concentration is a computer.

41. The method of claim 6, wherein the scaled, 2d derivative spectrum value corresponds to a wavelength of the spectral response at which the slope of a scaled second derivative spectrum derived from the spectral response is substantially identical to the slope of a plurality of scaled, second derivative spectra obtained for a plurality of other tissue samples characterized by different relative concentrations of the chromophore.

16. A method of measuring a relative concentration of a first form of a chromophore in a tissue sample, said chromophore comprising at least a first form and a second form, comprising the steps of:

(a) obtaining spectral data for said tissue sample over a plurality of wavelengths within a wavelength range within which the first and second forms of the chromophore provide an overlapping spectral response to irradiation with spectroscopic radiation;

(b) determining a first 2d derivative spectrum value of the spectral data at a first wavelength within said wavelength range at which the first 2d derivative spectrum value varies with the relative concentration of the first form of the chromophore;

(c) determining a second 2d derivative spectrum value of the spectral data at a second wavelength within said wavelength range at which the first 2d derivative spectrum value varies with the relative concentration of the first for-m of the chromophore;

(d) deriving a scaled, 2d derivative spectrum value from information comprising the first and second 2d derivative spectrum values;

(e) determining the relative concentration of the first form of the chromophore in the tissue sample from information comprising the scaled, 2d derivative spectrum value and a correlation which provides the relative concentration of the first form of the chromophore as a function of the scaled, 2d derivative spectrum value.

17. The method of claim 16, wherein the spectral data is obtained from the tissue sample in vivo.

18. The method of claim 16, wherein the scaled, 2d derivative spectrum value is a ratio between said first and second 2d derivative spectrum values.

19. The method of claim 16, wherein step (a) comprises irradiating the tissue sample with near infrared radiation in order to obtain the spectral response.

20. The method of claim 16, wherein said wavelength range is from about 600 nm to about 900 nm.

21. The method of claim 16, wherein step (a) comprises the steps of:

(i) providing a probe having a tissue sample interface surface for irradiating the tissue sample with the spectroscopic radiation and for receiving light emitted from the tissue sample in response to said irradiation;

(ii) providing a light source assembly for generating the spectroscopic radiation, said light source assembly comprising;

(1) a light source; and

(2) at least one send optical fiber optically coupling the light source to the tissue interface surface of the probe, wherein the send optical fiber has a light entry region disposed proximal to the light source for receiving the spectroscopic radiation and a light exit region coupled to the tissue sample interface surface of the probe for emitting the spectroscopic radiation onto the tissue sample;

(iii) irradiating the tissue sample with spectroscopic radiation transported to the tissue sample through the send optical fiber.

22. The method of claim 21, wherein the spectroscopic radiation is near infrared radiation.

23. The method of claim 21, wherein the tissue sample interface surface of the probe comprises a spectrally flat surface portion proximal to the send optical fiber.

24. The method of claim 21, wherein the tissue sample interface surface of the probe comprises polyphenylsulfone.

25. The method of claim 21, wherein the tissue sample interface surface of the probe comprises a reflective portion to amplify a shallow depth measurement of the tissue sample.

26. The method of claim 21, wherein the tissue sample interface surface of the probe comprises a non-reflective surface portion.

27. The method of claim 21, wherein the probe further comprises an antimicrobial black nylon fabric disposed proximal to the tissue sample interface surface of the probe.

28. The method of claim 21, wherein the probe further comprises an infrared cutoff filter disposed proximal to the tissue sample interface surface.

29. The method of claim 21, wherein the light source assembly further comprises a light source shroud for focusing the spectroscopic radiation emitted by the light source onto a focal area, and wherein the light entry region of said at least one send optical fiber is disposed at the focal area.

30. The method of claim 21, wherein the light source comprises a continuous wave broad bandwidth lamp capable of generating a spectrum sufficient to cover said plurality of wavelengths.

31. The method of claim 21, wherein the light source comprises a plurality of narrow bandwidth lamps having overlapping spectrums sufficient to cover said plurality of wavelengths.

32. The method of claim 21, wherein the light source assembly further comprises an optical fiber feedback loop comprising:

(i) a power sensor for sensing the output of the light source;

(ii) at least one feedback optical fiber optically coupling the light source to the power sensor; and

(iii) a control system interfaced with the light source and the power sensor such that the control system is capable of controllably adjusting the output of the light source in order to stabilize the amount of radiation emitted by the light source.

33. The method of claim 32, wherein the control system has a switching frequency substantially less than the thermal time constant of the light source.

34. The method of claim 16, wherein step (a) comprises the steps of:

(i) providing a fiber optic probe comprising a tissue sample interface surface;

(ii) providing at least one send optical fiber having a first region adapted for receiving the spectroscopic radiation from a light source and a second region coupled to the tissue sample interface surface of the probe for emitting the spectroscopic radiation onto the tissue sample;

(iii) providing at least one receive optical fiber having a first region coupled to the tissue sample interface surface of the probe for receiving light emitted from the tissue sample in response to irradiation with the spectroscopic radiation and a second region adapted to be optically coupled to a spectroscopic detector;

(iv) irradiating the tissue sample with spectroscopic radiation transported to the tissue sample through the send optical fiber; and

(v) determining the spectral response of the tissue sample from information comprising the spectroscopic radiation transported to the spectroscopic detector through the receive optical fiber.

35. The method of claim 34, wherein the send and receive optical fibers are coupled to the probe with a side firing configuration.

36. The method of claim 34, wherein the spectroscopic radiation is near infrared radiation.

37. The method of claim 34, further comprising

(i) using the fiber optic probe to obtain a reference spectrum;

and

(ii) deriving the scaled, 2d derivative spectrum value from information comprising the spectral response of the tissue sample and the reference spectrum.

38. The method of claim 37, wherein the step of using the fiber optic probe to obtain a reference spectrum comprises the steps of:

(i) positioning at least the tissue sample interface surface of the probe into a container having a spectrally flat material inside the container, said probe being positioned in the container in a manner such that ambient light is excluded from the container;

(ii) irradiating the spectrally flat material with spectroscopic radiation transported to the container through the send optical fiber;

(iii) using the receive optical fiber to receive light emitted from the spectrally flat material responsive to the irradiation and to transport the emitted light to the spectroscopic detector; and

(iv) determining the reference spectrum from information comprising the spectroscopic radiation emitted from the spectrally flat material and transported to the spectroscopic detector through the receive optical fiber.

39. The method of claim 37, further comprising the step of calibrating the fiber optic probe prior to obtaining the reference spectrum and prior to measuring the spectral response of the tissue sample.

40. The method of claim 39, wherein the step of calibrating the fiber optic probe comprises the steps of:

(i) positioning a filter in a canister having a spectrally flat material inside the container, wherein the filter is capable of emitting a spectral response comprising a plurality of spectral peaks at known wavelengths in response to irradiation with the spectroscopic radiation;

(ii) positioning at least the tissue sample interface surface of the probe into the container in a manner such that ambient light is excluded from the container;

(iii) irradiating the filter and spectrally flat material with spectroscopic radiation transported to the container through the send optical fiber;

(iv) using the receive optical fiber to receive light emitted from the filter and spectrally flat material responsive to the irradiation and to transport the emitted light to the spectroscopic detector; and

(v) calibrating the probe from information comprising the emitted light transported from the container to the spectroscopic detector through the receive optical fiber.

42. The method of claim 16, wherein step (a) further comprises the steps of:

(i) transforming the spectral response into a second derivative spectrum;

(ii) providing a scaling factor for scaling the second derivative spectrum; and

(iii) determining the scaled, 2d derivative spectrum value from information comprising the second derivative spectrum and the scaling factor.

43. The method of claim 42, wherein the scaling factor corresponds to the maximum amplitude value of the second derivative spectrum.

44. The method of claim 16, wherein the correlation is derived from scaled second derivative spectrum values obtained for a plurality of reference tissue samples and corresponding relative chromophore concentrations for the plurality of the reference tissue samples.

45. The method of claim 44, wherein the correlation is obtained by a method comprising the steps of:

(i) providing a plurality of the reference tissue samples, wherein said reference tissue samples are characterized by a plurality of different relative chromophore concentrations;

(ii) measuring the relative chromophore concentration of each of the reference tissue samples;

(iii) measuring the spectral response of each of the reference tissue samples over plurality of wavelengths within the wavelength range from 600 nm to 900 nm;

(iv) deriving a scaled, 2d derivative spectrum value for each of the reference tissue samples, wherein each of the scaled, 2d derivative spectrum values is obtained from information comprising the spectral data obtained for each reference tissue sample, respectively; and

(v) developing the correlation from information comprising the measured relative concentrations and the corresponding scaled, 2d derivative spectrum values.

46. The method of claim 45, wherein the spectral response of each of the reference tissue samples is obtained in a blood flow measurement system.

47. A system for measuring a relative concentration of a first form of a chromophore in a tissue sample, said chromophore comprising at least a first form and a second form, comprising:

(a) a memory comprising data representative of a correlation which provides the relative concentration of the first form of the chromophore as a function of a scaled, 2d derivative spectrum value input, wherein the scaled second derivative value input is derived from a spectral response obtained from the tissue sample at a plurality of wavelengths within a wavelength range from 600 nm to 900 nm;

(b) a light source assembly for generating spectroscopic radiation for irradiating the tissue sample;

(c) a spectroscopic detector for detecting the spectral response emitted by the tissue sample responsive to irradiation with the spectroscopic radiation; and

(d) a control system interfaced with the memory and the spectroscopic detector such that;

the control system generates the scaled, second derivative spectrum value of the tissue sample from information comprising the spectral response of the tissue sample; and

(ii) the control system generates information representative of the relative concentration of the first form of the chromophore in the tissue sample from information comprising the scaled, second derivative spectrum value and the correlation provided in the memory.

48. The system of claim 47, wherein the scaled, 2d derivative spectrum value is obtained from the tissue sample in vivo.

49. The system of claim 47, wherein the spectroscopic radiation is near infrared radiation.

50. The system of claim 47, wherein the system further comprises a probe having a tissue sample interface surface for irradiating the tissue sample with the spectroscopic radiation and for receiving light emitted from the tissue sample in response to said irradiation;

and wherein the system further comprises a light source assembly comprising;

(1) a light source for radiating the spectroscopic radiation; and

(2) at least one send optical fiber optically coupling the light source to the tissue interface surface of the probe, wherein the send optical fiber has a light entry region disposed proximal to the light source for receiving the spectroscopic radiation and a light exit region coupled to the tissue sample interface surface of the probe for emitting the spectroscopic radiation onto the tissue sample.

51. The system of claim 50 wherein the spectroscopic radiation is near infrared radiation.

52. The system of claim 50, wherein the tissue sample interface surface of the probe comprises a spectrally flat surface portion.

53. The system of claim 50, wherein the tissue sample interface surface of the probe comprises polyphenylsulfone.

54. The system of claim 50, wherein the tissue sample interface surface of the probe comprises a reflective portion to amplify a shallow depth measurement of the tissue sample.

55. The system of claim 54, wherein the light source assembly further comprises a light source shroud for focusing the spectroscopic radiation emitted by the light source onto a focal area, and wherein the light entry region of said at least one send optical fiber is disposed at the focal area.

56. The system of claim 50, wherein the tissue sample interface surface of the probe comprises a non-reflective surface.

57. The system of claim 50, further comprising an antimicrobial black nylon fabric dispose proximal to the tissue sample interface surface of the probe.

58. The system of claim 50, wherein the probe further comprises an infrared cutoff filter dispose proximal to the tissue sample interface surface.

59. The system of claim 50, wherein the light source comprises a continuous wave broad bandwidth lamp capable of generating a spectrum sufficient to cover said plurality of wavelengths.

60. The system of claim 50, wherein the light source comprises a plurality of narrow bandwidth lamps having overlapping spectrums sufficient to cover said plurality of wavelengths.

61. The system of claim 50, wherein the light source assembly further comprises an optical fiber feedback loop comprising:

(i) a power sensor for sensing the output of the light source;

(ii) at least one feedback optical fiber optically coupling the light source to the power sensor; and

wherein the control system is further interfaced with the light source and the power sensor such that the control system is capable of controllably adjusting the output of the light source in order to stabilize the amount of radiation emitted by the light source.

62. The system of claim 61, wherein the control system has a switching frequency substantially less than the thermal time constant of the light source.

63. The system of claim 50, further comprising at least one receive optical fiber having a first region coupled to the tissue sample interface surface of the probe and a second region coupled to the spectroscopic detector.

64. The system of claim 63, wherein the send and receive optical fibers are coupled to the probe with a side firing configuration.

65. The system of claim 63, further comprising a container having a spectrally flat material inside the container and an aperture adapted to receive the probe in a manner such that ambient light is excluded from the container and such that the probe is capable of irradiating the spectrally flat material with the spectroscopic radiation and receiving radiation reflected by said material responsive to irradiation.

66. The system of claim 65, wherein the system further comprises a filter disposed in the container, wherein the filter emits a spectral response comprising a plurality of spectral peaks at known wavelengths in response to irradiation with the spectroscopic radiation.

67. The system of claim 47, wherein the system further includes machine readable program instructions enabling the system to

(i) actuate the light source assembly and the spectroscopic detector to obtain a spectral response of the tissue sample;

(ii) transform the spectral response into a second derivative spectrum;

(iii) provide a scaling factor for scaling the second derivative spectrum; and

(iv) determine a scaled, 2d derivative spectrum value for the tissue sample from information comprising the second derivative spectrum and the scaling factor.

68. The system of claim 67, wherein the scaling factor corresponds to the maximum amplitude value of the second derivative spectrum.