Apparatus and method for monitoring tissue vitality parameters

• US 20040054270A1
• Filed: 03/25/2003
• Published: 03/18/2004
• Est. Priority Date: 09/25/2000
• Status: Active Grant

• Current Assignee: CritiSense Ltd.
• Original Assignee: CritiSense Ltd.
• Inventors: Pewzner, Eliahu, Mayevsky, Avraham
• Granted Patent: US 7,130,672 B2
• Time in Patent Office: Days
• US Class Current: 600/341
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue

Abstract

Apparatus for monitoring a plurality of tissue viability parameters of a tissue layer element, in which two different illumination sources are used via a common illumination element in contact with the tissue. One illumination source is used for monitoring blood flow rate and optionally flavoprotein concentration, and collection fibers are provided to receive the appropriate radiation from the tissue. The other illuminating radiation is used for monitoring any one of and preferably all of NADH, blood volume and blood oxygenation state of the tissue element, and collection fibers are provided to receive the appropriate radiation from the tissue. In one embodiment, the wavelengths of the two illumination sources are similar, and common collection fibers for the two illuminating radiations are used. In another embodiment, the respective collection fibers are distanced from the illumination point at different distances correlated to the ratio of the first and second illuminating wavelengths.

Claims

1. Apparatus for selectively monitoring at least two tissue viability parameters corresponding to a tissue element, the apparatus comprising:

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(a) a probe, comprising;

illumination means for illuminating at least said tissue element with a first illuminating radiation at a first wavelength and with a second illuminating radiation at a second wavelength via at least one common illumination location with respect to said tissue element;

first radiation receiving means for receiving a first radiation from said tissue element as a result of an interaction between said first illuminating radiation and said layer of tissue element, said first radiation being correlated to said blood flow rate tissue viability parameter, said first radiation receiving means being displaced from said illumination location by a first displacement;

second radiation receiving means for receiving at least a second radiation from said layer of tissue element as a result of an interaction between said second illuminating radiation and said layer of tissue element, aid second radiation being correlated to said at least one second tissue viability parameter, said second radiation receiving means being displaced from said illumination location by a second displacement

wherein said first displacement and said second displacement are selected such that;

said first radiation receiving means receive said first radiation corresponding to a first sampling depth of said first illuminating radiation in said tissue element, said first sampling depth being correlated to said first wavelength and said first displacement;

said second radiation receiving means receive said second radiation corresponding to a second sampling depth of said second illuminating radiation in said tissue element, said second sampling depth being correlated to said second wavelength and said second displacement; and

wherein said first sampling depth is substantially identical to said second sampling depth.

(b) a suitable first light source, operatively connected to said probe for providing said first illuminating radiation; and

(c) a second light source operatively connected to said probe for providing said second illuminating radiation.

2. Apparatus as claimed in claim 1, wherein said common illumination location is provided by at least one excitation optical fiber capable of being brought into registry with said tissue element.

3. Apparatus as claimed in claim 1, wherein a ratio of said first displacement to said second displacement is substantially correlated to a ratio of said second wavelength to said first wavelength.

4. Apparatus as claimed in claim 1, wherein said first wavelength is substantially different from said second wavelength.

5. Apparatus as claimed in claim 1, wherein said first radiation receiving means comprises at least one suitable first receiving optical fiber capable of being brought into registry with said tissue element.

6. Apparatus as claimed in claim 1, wherein said second radiation receiving means comprises at least one suitable second receiving optical fiber capable of being brought into registry with said tissue element.

7. Apparatus as claimed is claim 6, wherein aid at lest one excitation optical fiber, said at least one first receiving optical fiber and said at least one second receiving optical fiber are housed in a suitable probe head.

8. Apparatus as claimed in claim 1, wherein said first wavelength and said second wavelength have substantially similar penetration depth with respect to said tissue element.

9. Apparatus as claimed in claim 8, wherein a ratio of said first displacement to said second displacement is substantially unit.

10. Apparatus as claimed in claim 8, wherein said first wavelength is substantially the same as said second wavelength.

11. Apparatus as claimed in claim 10, wherein aid first radiation receiving means and said second radiation receiving means are comprised of at least one common third optical fiber capable of being brought into registry with said tissue element.

12. Apparatus as claimed in claim 11, wherein said common illumination location is provided by at least one excitation optical fiber capable of being brought into registry with said tissue element.

13. Apparatus as claimed in claim 12, wherein said at least one excitation optical fiber and said at least one common third optical fiber are housed in a suitable probe head.

14. Apparatus as claimed in any one of claims 1 to 13, further comprising suitable detection means operatively connected to said probe, wherein said detection means detects said first radiation and said second radiation.

15. Apparatus as claimed in claim 14, wherein said first light source comprises a coherent light source.

16. Apparatus as claimed in claim 15 wherein said blood flow rate tissue viability parameter is provided by the Doppler shift of said first radiation receiving by said first radiation receiving means with respect to the said first illuminating radiation.

17. Apparatus as claimed in claim 16, wherein said detection means comprises first detection means for detecting said first radiation receiving by said first radiation receiving means.

18. Apparatus as claimed in claim 14, wherein said second light source comprises a suitable monochromatic light source.

19. Apparatus as claimed in claim 18, wherein second wavelength is chosen to lie at a suitable isosbestic point.

20. Apparatus as claimed in claim 19, wherein said isosbestic point is within a substantially isosbestic range of the oxyhaemaglobin—

deoxyhaemaglobin absorption vs. wavelength curves.

21. Apparatus as claimed in claim 18, wherein said second wavelength is within the range of wavelengths corresponding to a NADH excitation spectrum.

22. Apparatus as claimed in claim 18, wherein said second wavelength is between about 300 nm and about 395 nm, and preferably between about 300 nm and about 340 nm.

23. Apparatus as claimed in claim 18, wherein said second wavelength is within about ±

6 nm of any of the following wavelengths;

325 nm, 397 nm, 349 nm, 355 nm, 366 nm, 370 nm, 385 nm or 390 nm.

24. Apparatus as claimed in claim 14, wherein said first wavelength is between about 300 nm and about 440 nm.

25. Apparatus as claimed in claim 14, wherein said first wavelength is greater than about 440 nm.

26. Apparatus as claimed in claim 14, wherein said first wavelength is either in the range 410±

30 nm or within about ±

5 nm of any one of the following wavelengths;

355 nm, 430 nm, 440 nm, 455 nm, 460 nm, 490 nm, 532 nm or 305 nm.

27. Apparatus as claimed in claim 18, wherein said radiation of said second wavelength is provided by any suitable UV light source.

28. Apparatus as claimed in any one of claims 14 to 27, wherein a said at least one second tissue viability parameter is NADH concentration, and said corresponding second radiation receiving by said second radiation receiving means is a NADH fluorescence emitted by the tissue element corresponding to said second sampling depth in response to illumination thereof by said second illuminating radiation, said at least one second tissue viability parameter being provided by the intensity of said NADH fluorescence.

29. Apparatus as claimed in claim 28, wherein said detection means comprises second detection means for detecting said second radiation received by said second radiation receiving means.

30. Apparatus as claimed in any one of claims 14 to 27, wherein a said at least one second tissue viability parameter is blood volume within said tissue element, and said corresponding second radiation received by said second radiation receiving means is a reflection from the tissue element corresponding to said second sampling depth in response to illumination thereof by said second illuminating radiation;

the said at least one second tissue viability parameter being provided by the intensity of said reflection.

31. Apratus as claimed in claim 30, wherein said detection means comprises third detection means for detecting said second radiation receiving by said second radiation receiving means.

32. Apparatus as claimed in any one of claims 14 to 27, wherein a said at least one second tissue viability parameter is blood oxygenation ratio within said tissue element, and said corresponding second radiation received by said second radiation receiving means is a fluorescence emitted by the tissue element corresponding to said second sampling depth in response to illumination thereof by said second illuminating radiation, said at least one second tissue viability parameter being provided by the intensity of said fluorescence at least at two fluorescent wavelengths.

33. Apparatus as claimed in claim 32, wherein one of said at least two fluorescent wavelengths is chosen to lie at an oxy-deoxy fluorescence emission isosbestic point.

34. Apparatus as claimed in claim 32, wherein one of said at least two fluorescent wavelengths is higher and another one of said at least two fluorescent wavelengths is smaller than a wavelength corresponding to an oxy-deoxy fluorescence emission isosbestic point.

35. Apparatus as claimed in claim 32, wherein said detection means comprises fourth detection means for detecting said second radiation received by said second radiation receiving means.

36. Apparatus as claimed in claim 14, for further monitoring a flavoprotein concentration tissue vitality parameter, comprising fifth detection means for detecting a portion of said first radiation received by said first radiation receiving means, said portion of said received first radiation being a flavoprotein fluorescence emitted by the said tissue element in response to illumination thereof by said first illuminating radiation, said flavoprotein tissue viability parameter being provided by the intensity of said flavoprotein fluorescence.

37. Apparatus as claimed in claim 36, wherein said first wavelength is within the range of wavelengths corresponding to a flavoprotein excitation spectrum.

38. Apparatus as claimed in claim 36, wherein said first wavelength is between about 400 nm and about 470 nm, and preferably between about 440 nm and 460 nm.

39. Apparatus as claimed in claim 15, wherein said first coherent light source is a laser light source.

40. Apparatus as claimed in claim 39, wherein said laser light source is adapted to provide said first illuminating radiation of said first wavelength in pulses of predetermined duration and intensity.

41. Apparatus as claimed in claim 40, further comprising suitable control means for controlling the frequency of pulsing of said pulses.

42. Apparatus as claimed in claim 41, wherein said control means is further adapted to provide said pulses in packages of pulses, each package comprising at least one pulse and separated from a preceding or following package by a predetermined time period.

43. Apparatus as claimed in claim 42, wherein said predetermined time period is greater than the time interval between consecutive pulses within a package.

44. Apparatus as claimed in claim 43, wherein said time period is controllably variable.

45. Apparatus as claimed in claim 42, wherein the number of pulses within each package is controllably variable.

46. Apparatus as claimed in claim 42, wherein said control means is operatively connected to at least one of said first detection means, second detection means, said third detection means and fourth detection means.

47. Apparatus as claimed in claim 41, wherein said control means is selectively responsive to previously detected signals corresponding to the detection of said second radiation detected by means of any one of said second detection means, said third detection means or said fourth detection means, of a prior monitoring cycle.

48. A system for selectively monitoring at least two tissue viability parameters at a plurality of tissue elements;

said system comprising a plurality of monitoring probes as defined in any one of claims 1 to 18, and wherein each said probe of said plurality of probes is operatively connected to an apparatus as defined in any one of claims 14 to 47.

49. A system as claimed in claim 48, wherein at least two said probes are adapted for monitoring said tissue viability parameters of tissue elements within the same organ.

50. A system as claimed in claim 48, wherein at least two said probes are adapted for monitoring said tissue viability parameters of tissue elements within different organs.

51. A system as claimed in claim 50, wherein different organs are different organs within the same organism.

52. A system as claimed in claim 50, wherein different organs are different organs within different organisms.

53. A system as claimed in claim 50, wherein different organs are different organs include donor organs.

54. A system as claimed in claim 48, wherein said second illuminating radiation of said second wavelength for each said probe is provided by a common suitable second light source.

55. A system as claimed in claim 54, wherein said second light source is a suitable UV monochromatic light source.

56. A system as claimed in claim 55, wherein said UV light source is adapted to provide said second illuminating radiation of said second wavelength in first pulses of predetermined duration and intensity.

57. A system as claimed in claim 48, wherein said first illuminating radiation of said first wavelength for each said probe is provided by a common suitable first light source.

58. A system as claimed in claim 57, wherein said first light source is a laser light source.

59. A system as claimed in claim 58, wherein said laser light source is adapted to provide said first illuminating radiation of said first wavelength in second pulses of predetermined duration and intensity.

60. A system as claimed in claim 59, further comprising suitable control means for controlling the frequency of pulsing of said second pulses.

61. A system as claimed in claim 60, wherein said control means is further adapted to provide said second pulses in packages of pulses, each package comprising at least one second pulse and separated from a preceding or following package by a predetermined time period.

62. A system as claimed in claim 61, wherein said predetermined time period is greater than the time interval between consecutive pulses within a package.

63. A system as claimed in claim 61, wherein aid time period is controllably variable.

64. A system as claimed in claim 60, wherein the number of second pulses within each package is controllably variable.

65. A system as claimed in claim 60, wherein said control means is adapted for selectively directing discrete said second pulses to any one of said probes.

66. A system as claimed in claim 60, further comprising suitable first common detection means for detecting said first radiation received by said first radiation receiving means of at least two said probes, and coupling means for optically connecting said at least two probes to said first common detection means.

67. A system as claimed in claim 60, further comprising suitable second common detection means for detecting said second radiation received by said second radiation receiving means of at least two said probes, and coupling means for optically connecting said at least two probes to said second common detection means, wherein said second tissue viability parameter corresponding to said second radiation is NADH concentration.

68. A system as claimed in claim 60, further comprising suitable third common detection means for detecting said second radiation received by said second radiation receiving means of at least two probes, and coupling means for optically connecting said at least two probes to said third common detection means, wherein said second tissue viability parameter corresponding to said second radiation is blood volume.

69. A system as claimed in claims 60, further comprising suitable fourth common detection means for detecting said second radiation received by said second radiation receiving means of at least two said probes, and coupling means for optically connecting said at least two probes to said fourth common detection means, wherein said second tissue viability parameter corresponding to said second radiation is blood oxygenation ratio.

70. A system as claimed in claims 60, further comprising suitable fifth common detection means for detecting a portion of said first radiation received by said first radiation receiving means of at least two said probes, said portion of said received first radiation being a flavoprotein fluorescence emitted by the said tissue element in response to illumination thereof by said first illuminating radiation, said flavoprotein tissue viability parameter being provided by the intensity of said flavoprotein fluorescence, said system further comprising coupling means for optically connecting said at least two probes to said fifth common detection means.

71. A system as claimed in claim 66, wherein said control means is operatively connected to said first common detection means.

72. A system as claimed in claim 67, wherein said control means is operatively connected to said second common detection means.

73. A system as claimed in claim 72, wherein said control means is selectively responsive to previously detected signals corresponding to the detection of said second radiation detected by aid second common detection means of a prior monitoring cycle.

74. A system as claimed in claim 68, wherein said control means is operatively connected to said third common detection means.

75. A system as claimed in claim 74, wherein said control means is selectively responsive to previously detected signals corresponding to the detection of said second radiation detected by said third common detection means of a prior monitoring cycle.

76. A system as claimed in claim 69, wherein said control means is operatively connected to said fourth common detection means.

77. A system as claimed in claim 78, wherein said control means is selectively responsive to previously detected signals corresponding to the detection of said second radiation detected by said fourth common detection means of a prior monitoring cycle.

78. A system as claimed in claim 70, wherein said control means is operatively connected to said fifth common detection means.

79. A system as claimed in clam 78, wherein said control means is selectively responsive to previously detected signals corresponding to the detection of said first radiation detected by said fifth common detection means of a prior monitoring cycle.

80. Method for determining the oxygenation state of a tissue element, comprising:

(a) providing an illuminating radiation to the tissue element, said illuminating radiation being at a wavelength within one of the NADH excitation spectrum or the Fp excitation spectrum;

(b) measuring the intensity of the corresponding NADH fluorescence or Fp fluorescence respectively, emitted by the tissue element at least at two predetermined wavelengths within the range of wavelengths comprised in the corresponding fluorescence emission;

(c) comparing the intensities measured in (b) to provide an estimate of the relative levels of oxygenated blood to deoxygenated blood in said tissue element.

81. Method as claimed in claim 80, wherein one of said wavelengths in step (b) is chosen to lie at a suitable NADH oxy-deoxy fluorescence emission isosbestic point or Fp oxy-deoxy fluoresence emission isosbestic point, respectively.

82. Method as claimed in claim 81, wherein the intensity of fluorescence emitted by the tissue element at two target wavelengths within the range of wavelengths comprised in the fluorescence is measured, wherein a first target wavelength thereof is chosen at below the wavelength corresponding to said NADH oxy-deoxy fluoresence emission isosbestic point or Fp oxy-deoxy fluoresence emission isosbestic point, respectively, and wherein a second target wavelength thereof is chosen at above the wavelength corresponding to said NADH oxy-deoxy fluoresence emission isosbestic point or Fp oxy-deoxy fluoresence emission isosbestic point, respectively.

83. Method as claimed in claim 82, wherein the said first target wavelength and said second target wavelength are chosen such as to correspond to the maximal change in fluorescence intensity occurring at wavelengths below and above, respectively of said NADH oxy-deoxy fluorescence emission isosbestic point or Fp oxy-deoxy fluoresence emission isosbestic point, respectively.

84. Method as claimed in claim 80, wherein the intensity of fluorescence emitted by the tissue element is measured over a range of wavelengths within a specific window of the range of wavelengths comprises in the fluorescence.

85. Method as claimed in claim 80, wherein in step (c) the fluorescence intensity at each wavelength in (b) is normalised by a normalising fluorescence intensity measured at a suitable corresponding NADH or Fp oxy-deoxy fluorescence emission isosbestic wavelength within the fluorescence emission spectrum.

86. Method as claimed in claim 80, wherein said illuminating radiation is provided at a suitable NADH oxy-deoxy fluoresence excitation isosbestic wavelength or a suitable Fp oxy-deoxy fluoresence excitation isosbestic wavelength, respectively within the corresponding NADH fluoresence excitation spectrum or Fp fluorescence excitation spectrum, respectively.

87. Method as claimed in any one of claims 80 to 86, wherein said illuminating radiation in step (a) is within the range of wavelengths comprises in the NADH excitation spectrum.

88. Method as claimed in claim 87, wherein said normalising fluorescence intensity is measured at an oxy-deoxy fluorescence emission isosbestic wavelength of about 455 nm±

5 nm.

89. Method as claimed in any one of claims 80 to 86, wherein said illuminating radiation in step (a) is within the range of wavelengths comprises in the Fp excitation spectrum.

90. Method as claimed in claim 89, wherein said normalising fluorescence intensity is measured at an oxy-deoxy fluorescence emission isosbestic wavelength of about 530 nm±

5 nm.

91. Apparatus for determining the oxygenation sate of a tissue element, comprising:

(a) illumination means for illuminating said tissue element with an illuminating radiation at a predetermined wavelength via one illumination location with respect to said tissue element, said illuminating radiation being at a wavelength within on of the NADH excitation spectrum or the Fp excitation spectrum;

(b) radiation receiving means and detection means for measuring the intensity of he corresponding NADH fluorescence or Fp fluorescence emitted by the tissue element at least tat two predetermined wavelengths within the range of wavelengths comprised in the corresponding fluorescence emission, said receiving means being distanced from said illumination location by a first displacement.

92. Apparatus as claimed in claim 91, further comprising suitable means adapted for comprising the intensities measured in (b) to provide an estimate of the relative levels of oxygenated blood to deoxygenated blood in said tissue element.

93. Apparatus as claimed in claim 91, wherein said receiving means and said detection means are adapted for measuring said intensity at said at least two fluorescent wavelengths such that one of said fluorescent wavelengths is at an oxy-deoxy fluorescence emission isosbestic point in the fluorescent emission spectrum.

94. Apparatus as claimed in claim 91, wherein said receiving means and said detection means are adapted for measuring said intensity at said at least two fluorescent wavelengths, such that one of said fluorescent wavelengths is higher than, and another one of said at least two fluorescent wavelengths is smaller than, a wavelength corresponding to an oxy-deoxy fluorescence emission isosbestic point in the fluorescent emission spectrum.

95. Apparatus as claimed in claim 91, wherein said predetermined wavelength of said illuminating radiation corresponds to an isosbestic point of the excitation spectrum.

96. Apparatus as claimed in claim 91, wherein said illumination location is provided by at least one excitation optical fiber capable of being brought into registry with said tissue element.

97. Apparatus as claimed in claim 95, wherein said radiation receiving means comprises at least one suitable first receiving optical fiber capable of being brought into registry with said tissue element.

98. Apparatus as claimed in claim 96, wherein said at least one excitation optical fiber, said at lest one receiving optical fiber are housed in a suitable probe head.