Optical spectroscopy for the detection of ischemic tissue injury

• US 20050171414A1
• Filed: 01/08/2005
• Published: 08/04/2005
• Est. Priority Date: 01/08/2004
• Status: Active Grant

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Troppmann, Christoph, Michalopoulou, Andromachi, Fitzgerald, Jason, Demos, Stavros
• Granted Patent: US 7,587,236 B2
• Time in Patent Office: Days
• US Class Current: 600/315
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient'"'"'s body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

Claims

1. A method for assessing tissue parameters, comprising:

illuminating a desired tissue component region with a first substantially narrow spectral band source;

illuminating said desired tissue component region with a second substantially narrow spectral band source, wherein said illuminated region by said first and said second substantially narrow spectral band sources comprises an area of greater than about 1.5 mm²;

detecting a respective autofluorescence emission from said desired illuminated region induced by said first and said second substantially narrow spectral band sources; and

comparing intensities of said respective autofluorescence emission to assess in real-time at least one parameter selected from;

tissue properties, the metabolic state, injury, and tissue property changes resulting from therapeutic or prophylactic intervention of said tissue component region.

2. The method of claim 1, wherein said autofluorescence emission from said tissue component region comprises a spectral region between about 400 nm and about 1000 nm.

3. The method of claim 1, wherein said autofluorescence emission from said tissue component region comprises a spectral region between about 290 nm and about 800 nm.

4. The method of claim 1, wherein said autofluorescence comprises an emission from a biological fluorophore.

5. The method of claim 1, wherein said first and said second substantially narrow spectral band sources comprise a monochromatic light source.

6. The method of claim 5, wherein said monochromatic light source can emit a wavelength of at least 250 nm.

7. The method of claim 5, wherein said first substantially narrow spectral band source comprises a wavelength within the absorption spectrum of NADH.

8. The method of claim 5, wherein said second substantially narrow spectral band source comprises a wavelength within the absorption spectrum of tryptophan.

9. The method of claim 1, wherein a source for said first and/or said second substantially narrow spectral bands comprises a broad band lamp designed to transmit predetermined filtered wavelengths.

10. The method of claim 1, wherein said illuminating steps comprises directing said first and said substantially narrow spectral bands via an optical fiber bundle so as to substantially illuminate an area having a long dimension of up to about 10 cm.

11. The method of claim 10, wherein said optical fiber bundle is adapted for receiving a scattered radiation and said autofluorescence.

12. The method of claim 1, wherein said detecting step comprises hyperspectral microscopy to image tissue microstructure and assess microscopic alterations associated with tissue injury.

13. The method of claim 1, wherein said tissue component region is in a state of ischemia.

14. The method of claim 1, wherein said tissue component region is in a state of hypoxia.

15. The method of claim 1, wherein said first and second substantially narrow spectral band sources are polarized and said autofluorescence emission from said tissue component region is analyzed.

16. The method of claim 1, wherein said first and second substantially narrow spectral band sources are linearly polarized and a parallel-polarized component of said autofluorescence emission is analyzed.

17. The method of claim 16, wherein a perpendicularly polarized component of said autofluorescence emission is analyzed.

18. The method of claim 1, wherein said autofluorescence emission having an opposite circular polarization orientation with respect to said substantially narrow spectral band sources is analyzed.

19. The method of claim 1, wherein said first and said second substantially narrow spectral band sources are elliptically polarized and a same elliptical polarization orientation of said autofluorescence emission is analyzed.

20. The method of claim 19, wherein an orthogonal elliptical polarization of said autofluorescence emission is analyzed.

21. The method of claim 1, wherein said first and second substantially narrow spectral band sources are polarized and a scattered electromagnetic radiation is analyzed.

22. The method of claim 21, wherein an orthogonal polarization component of said scattered electromagnetic radiation is analyzed.

23. The method of claim 1, wherein said detecting step comprises a charge coupled device.

24. The method of claim 1, wherein said detecting step comprises a device selected from a photomultiplier and a photodiode.

25. The method of claim 1, wherein said injured and uninjured tissue components comprise at least one tissue component selected from brain, kidney, liver, heart, bowel, skin, stomach, pancreas, and muscle.

26. The method of claim 1, wherein a fluorescing contrast agent can be infused into said tissue components to determine a quantifiable measurement of tissue injury.

27. An apparatus for assessing tissue parameters, comprising:

a source of electromagnetic radiation configured to produce at least two predetermined substantially narrow spectral bands;

a radiation source conduit adapted for directing said substantially narrow spectral bands so as to illuminate a same tissue component region with a source beam area of greater than about 1.5 mm² and induce autofluorescence, wherein said conduit is additionally adapted for receiving and directing said autofluorescence; and

a device adapted to record said received autofluorescence from said tissue component region; and

means for comparing intensities of said recorded autofluorescence emission from said same tissue component region to assess in real-time, at least one parameter selected from;

tissue properties, the metabolic state, injury, and tissue property changes resulting from therapeutic or prophylactic intervention of said tissue component region.

28. The apparatus of claim 27, wherein said source comprises one or more lasers having wavelengths at least greater than 250 nm.

29. The apparatus of claim 27, wherein said source further comprises one or more commercially available compact lasers.

30. The apparatus of claim 29, wherein said compact lasers comprise laser diodes.

31. The apparatus of claim 27, wherein said source comprises a broad band optical lamp designed to transmit predetermined filtered wavelengths.

32. The apparatus of claim 27, wherein said autofluorescence emission from said tissue component region comprises a spectral band between about 400 nm and about 1000 nm.

33. The apparatus of claim 27, wherein said autofluorescence emission from said tissue component region comprises a spectral band between about 290 nm and about 800 nm.

34. The apparatus of claim 27, wherein said autofluorescence comprises an emission from a biological fluorophore.

35. The apparatus of claim 27, wherein said substantially narrow spectral bands comprise a wavelength within the absorption spectrum of NADH.

36. The apparatus of claim 27, wherein said substantially narrow spectral bands comprise a wavelength within the absorption spectrum of tryptophan.

37. The apparatus of claim 27, wherein hyperspectral microscopy can be utilized to image tissue microstructure and assess microscopic alterations associated with said injured tissue components.

38. The apparatus of claim 27, wherein said tissue component region is in a state of ischemia.

39. The apparatus of claim 27, wherein said tissue component region is in a state of hypoxia.

40. The apparatus of claim 27, wherein said first and second substantially narrow spectral bands are polarized and said autofluorescence emission from said same tissue component region is analyzed.

41. The apparatus of claim 27, wherein said first and second substantially narrow spectral bands are linearly polarized and a parallel-polarized component of said autofluorescence emission from said same tissue component region is analyzed.

42. The apparatus of claim 41, wherein a perpendicularly polarized component of said autofluorescence emission from said same tissue component region is analyzed.

43. The apparatus of claim 27, wherein said autofluorescence emission having an opposite circular polarization orientation with respect to said substantially narrow spectral bands is analyzed.

44. The apparatus of claim 27, wherein said first and said second substantially narrow spectral bands are elliptically polarized and a same elliptical polarization orientation of said autofluorescence emission is analyzed.

45. The apparatus of claim 44, wherein an orthogonal elliptical polarization of said autofluorescence emission is analyzed.

46. The apparatus of claim 27, wherein said first and second substantially narrow spectral bands are polarized and a scattered electromagnetic radiation is capable of being analyzed.

47. The apparatus of claim 46, wherein an orthogonal polarization component of said scattered electromagnetic radiation is analyzed.

48. The apparatus of claim 27, wherein said device comprises a charge coupled device.

49. The apparatus of claim 27, wherein said device comprises at least one detector selected from a photomultiplier and a photodiode.

50. The apparatus of claim 27, wherein said same tissue component region comprises at least one tissue component selected from brain, kidney, liver, heart, bowel, stomach, skin, pancreas, and muscle.

51. The apparatus of claim 27, wherein said source conduit comprises an optical fiber bundle.

52. The apparatus of claim 51, wherein said fiber bundle comprises at least one illumination fiber having a diameter between about 500 microns and about 1 mm.

53. The apparatus of claim 51, wherein said fiber bundle comprises one or more optical fibers for receiving a scattered radiation and said autofluorescence.

54. The apparatus of claim 52, wherein said illumination fiber is arranged to illuminate a tissue area having a long dimension of up to about 10 cm.

55. An apparatus for assessing tissue parameters, comprising:

one or more laser sources having predetermined wavelengths;

an optical fiber bundle adapted for directing said laser sources from a proximal end to produce autofluorescence at a distal end in a same tissue component region and additionally adapted for receiving said autofluorescence at said distal end;

a protective sheath configured on said optical fiber bundle and adapted for positioning said distal end of said optical fiber bundle with respect to said tissue components and additionally adapted for redirecting said produced autofluorescence outside of the acceptance angle of said distal end of said optical fiber bundle so as to additionally be received for recordation;

a device adapted to record said received autofluorescence from said tissue components; and

means for comparing intensities of said recorded autofluorescence from said same tissue component region to assess in real-time, at least one parameter selected from;

tissue properties, the metabolic state, injury, and tissue property changes resulting from therapeutic or prophylactic intervention of said tissue component region.

56. The apparatus of claim 55, wherein said laser sources comprise wavelengths at least greater than 250 nm.

57. The apparatus of claim 55, wherein said sources further comprise one or more commercially available compact lasers.

58. The apparatus of claim 55, wherein said sources further comprise a diode monochromatic light source.

59. The apparatus of claim 55, wherein said sources comprise a broad band optical lamp designed to transmit predetermined filtered wavelengths.

60. The apparatus of claim 55, wherein said autofluorescence from said injured tissue comprises a spectral region between about 400 nm and about 1000 nm.

61. The apparatus of claim 55, wherein said autofluorescence from said uninjured tissue comprises a spectral region between about 290 nm and about 800 nm.

62. The apparatus of claim 55, wherein said autofluorescence comprises an from a biological fluorophore.

63. The apparatus of claim 55, wherein at lest one of said laser sources comprises a wavelength within the absorption spectrum of NADH.

64. The apparatus of claim 55, wherein at least one of said laser sources comprises a wavelength within the absorption spectrum of tryptophan.

65. The apparatus of claim 55, wherein hyperspectral microscopy can be utilized to image tissue microstructure and assess microscopic alterations associated with said injured tissue components.

66. The apparatus of claim 55, wherein said tissue component region is in a state of ischemia.

67. The apparatus of claim 55, wherein said tissue component region is in a state of hypoxia.

68. The apparatus of claim 55, wherein said laser sources comprise a polarized output and said autofluorescence from said same tissue component region is analyzed.

69. The apparatus of claim 55, wherein said laser sources comprise a linearly polarized output and a parallel-polarized component of said autofluorescence from said same tissue component region is analyzed.

70. The apparatus of claim 69, wherein a perpendicularly polarized component of said autofluorescence from said same tissue component region is analyzed.

71. The apparatus of claim 55, wherein said autofluorescence having an opposite circular polarization orientation with respect to said laser sources output is analyzed.

72. The apparatus of claim 55, wherein said laser sources are elliptically polarized and a same elliptical polarization orientation of said autofluorescence is analyzed.

73. The apparatus of claim 72, wherein an orthogonal elliptical polarization of said autofluorescence is analyzed.

74. The apparatus of claim 55, wherein an output of said laser sources is polarized and a scattered electromagnetic radiation is capable of being analyzed.

75. The apparatus of claim 74, wherein an orthogonal polarization component of said scattered electromagnetic radiation is analyzed.

76. The apparatus of claim 55, wherein said device comprises a charge coupled device.

77. The apparatus of claim 55, wherein said device comprises at least one detector selected from a photomultiplier and a photodiode.

78. The apparatus of claim 55, wherein said injured and uninjured tissue components comprise at least one tissue component selected from brain, kidney, liver, heart, bowel, stomach, skin, pancreas, and muscle.

79. The apparatus of claim 55, wherein said optical fiber bundle comprises at least one illumination fiber having a diameter between about 500 microns and about 1 mm.

80. The apparatus of claim 79, wherein said at least one illumination fiber is arranged to illuminate a tissue area having a long dimension of up to about 10 cm.

81. The apparatus of claim 55, wherein said optical fiber bundle comprises one or more optical fibers for receiving a scattered radiation and said autofluorescence.

82. The apparatus of claim 55, wherein said protective sheath further comprises a material adapted for transmitting ultra violet.

83. The apparatus of claim 55, wherein said protective sheath further comprises a reflective material to enable the redirection of said produced autofluorescence outside of the acceptance angle of said optical fiber bundle.

84. The apparatus of claim 83, wherein said reflective material comprises a polished metal.

85. The apparatus of claim 83, wherein said reflective material comprises a reflective coating.