Transcranial examination of the brain

• US 20020161290A1
• Filed: 06/27/2002
• Published: 10/31/2002
• Est. Priority Date: 05/18/1992
• Status: Active Grant

• Current Assignee: Non-Invasive Technology Incorporated
• Original Assignee: Non-Invasive Technology Incorporated
• Inventors: Chance, Britton
• Granted Patent: US 6,785,568 B2
• Time in Patent Office: Days
• US Class Current: 600/323
• 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 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/7257 using Fourier transforms

Abstract

One preferred embodiment utilizes differential measurement of radiation that migrated in two migration paths between two source (100) detector (110) pairs placed on the head in a manner that each path is localized in a portion of one hemisphere. The present invention also provides in various embodiments of spectrophotometer systems for in vivo examination of a tissue of a human by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the tissue. Generally, the spectrophotometer systems comprise a light source for introducing the radiation into the tissue, a detector for detecting radiation that has migrated in the tissue, processing means for processing signals of the detected radiation to create processed data, and evaluation means for determining physiological or pathophysiological changes in the

Claims

1. An oximeter for determining the oxygenation state of localized body tissue per se, constructed to be worn over a period of activity by a user and comprising a flexible, body-conformable support member which supports, adjacent the skin of a user, over the localized tissue of interest, at least a pair of spaced apart light sources, and intermediate thereof, at least a pair of wavelength-specific photo detectors, each light source exposed to transmit wavelengths of both of said specific wavelengths toward the localized tissue of interest lying below the skin and below the associated subcutaneous fat layer of the user, and each detector exposed to receive photons of the respective specific wavelength that have originated from each light source, and scattered from the localized tissue and passed back to the detectors through the subcutaneous fat layer and skin of the user, the support member including conformable barrier means disposed between each light source and the detectors, said barrier means being of substance capable of conforming to the contour of the wearer and preventing light energy proceeding laterally in the region of the barrier means from reaching the detectors.

3. The oximeter of claim 1 or 2 in which the light sources comprise broad spectrum CW light sources.

4. The oximeter of claim 3 in which the light sources comprise tungsten filament lamps.

5. The oximeter of claim 1 or 2 including control means for simultaneously flashing the light sources to enable each detector to pick up light energy at its specific wavelength simultaneously from each light source.

6. The oximeter of claim 1 or 2 including means constructed to flash said light sources at selected intervals unrelated to the interval of heart beats of the user.

16. The oximeter of claim 1, 2, 7 or 8 including electronic control circuitry for said light source and said detector means, the circuitry disposed upon a miniature semiconductor chip carried by said support member.

17. The oximeter of claim 1, 2, 7 or 8 in combination with a real-time readout device constructed to be worn by the user and having a display responsive to said oximeter disposed for viewing by the user.

19. The oximeter of claim 1, 2, 7 or 8 in combination with radio frequency telemetry means for transmitting oximeter data on a real time basis to a station remote from the user or to a receiver in a readout device constructed to be worn by a user.

20. The oximeter of claim 1, 2, 7 or 8 including electronic control circuitry for said light source and said detector means, the circuitry disposed upon a miniature semiconductor chip carried by said support member in combination with radio frequency telemetry means controlled by said circuitry for transmitting oximeter data on a real time basis to a station remote from the user.

21. The oximeter of claim 1, 2, 7 or 8 including means for battery-operation of said oximeter and means to record oximetry data in internal digital memory for subsequent display or data analysis on a computer.

22. The oximeter of claim 1, 2, 7 or 8 including electronic control circuitry for said light source and said detector means, the circuitry disposed upon a miniature semiconductor chip carried by said support member, and means for battery-operation of said oximeter and means to record oximetry data in internal digital memory for subsequent display or data analysis on a computer.

27. The method of claim 26 wherein said oximeter is constructed to monitor the trend of oxygen level in the brain, and means to evaluate the rate of change being detected and using said rate of change as the control value and alarm reference.

29. The method of claim 28 wherein the oximeter sensor is taped comfortably to the head for monitoring.

30. The method of claim 28 used in conjunction with impedance pneumography (breathing rate measurement using chest-wall impedance) and/or EKG to provide an effective in-home apnea monitor to alarm the patient or other individuals in the area so as to wake the patient and prevent hypoxic tissue damage during sleep.

33. The method of emergency monitoring of cerebral tissue oxygen level and blood volume in an emergency care situation with the device of claim 21.

34. The method of employing the device of any of the claims 1, 2, 7, or 8 wherein the oxygen levels, blood volume, and/or rate of charge are measured in cancerous tissue to indicate the activity and viability of the tissue.

35. The method of employing the device of claim 24 wherein the oxygen levels and blood volume are measured in cancerous tissue to indicate the activity and viability of the tissue.

36. The method of claim 34 including monitoring of the viability of a tumor following treatment intended to wipe out said cancerous tissue.

38. The helmet of claim 37 wherein the oximeter includes control circuitry on a miniature chip.

39. The helmet of claim 37 or 38 including means for determining the rate of change of oximetry readings and for comparing the rate of change to a standard.

42. The oximeter of claim 1, 2, 7 or 8 including electronic control circuitry comprised of entirely non-magnetic components enabling use of the device in conjunction with nuclear magnetic resonance imaging.

44. The oximeter of claim 1, 2, 7, or 8 including a water impermeable coating about said device for applications in the presence of water.

45. The oximeter of claim 1, 2, 7, or 8 wherein said light source comprises a light emitting diode.

46. The oximeter of claim 1, 2, 7, or 8 wherein said detector comprises a silicon diode.

47. The oximeter of claim 1 or 2 wherein said wavelength specific detector comprises a silicon diode and an interference filter.

48. The oximeter of claim 1, 2, 7, or 8 including electronic control circuitry for said light source and said detector, said circuitry being adapted to correct for a noise signal not attributable to detected light that migrated through said localized tissue of interest.

49. The oximeter of claim 48 wherein said correction of said noise signal being achieved by charging a capacitor of an integrator for said detector with current of one polarity during a light off cycle and subsequently charging said capacitor with current of opposite polarity during a light on cycle, whereby subtracting said noise signal occurring during said light off cycle from the total signal occurring during said light on cycle.

2. An oximeter for determining the oxygenation state of localized body tissue per se, constructed to be worn over a period of activity by a user and comprising a flexible support member which supports, over the localized tissue of interest, at least a pair of spaced apart light sources, and intermediate thereof, at least a pair of wave length-specific light detectors, each light source exposed to transmit wavelengths of both of said specific wavelengths toward the localized tissue of interest, and each detector exposed to receive photons of the respective specific wavelength that have originated from each light source, and scattered from the localized tissue and passed back to the detectors.

93. A cognition spectrophotometer system for transcranial examination of brain activity by measuring changes in light scattered and absorbed in a migration path in the brain comprising

(a) the oximeter of claim 2 or 7,

(b) stimulation means adapted to cause stimulation of a brain activity while introducing said light using said light source and while detecting said light that migrated in the localized tissue of interest of the brain,

(d) processing means adapted to process signals of said detected light that has migrated in the brain to create processed data, and

(e) evaluation means adapted to determine a characteristic of said brain activity by correlating said processed data to said caused stimulation of said brain activity.

7. An oximeter comprising a flexible support member comprised of a molded-elastomeric backing member, said backing member mounting at least one light source means capable of producing two selected wavelengths and oriented to direct said light to tissue of a user and said backing member mounting detector means capable of separately detecting energy at each of said wavelengths scattered by tissue of the user, integral elastomeric portions of said backing member defining a barrier exposed for conformable contact with an exposed surface of the user, in position to prevent lateral movement of light in subcutaneous layers from the source means to the detector means.

12. The oximeter of claim 7 or 8 wherein said barrier member comprises a rib-form member.

13. The oximeter of claim 7 or 8 including in series at least two barrier members, one closely adjacent to said light source means and one closely adjacent to said detector means.

14. The oximeter of claim 7 or 8 in which said support member mounts two spaced-apart light sources and a pair of detectors are disposed parallel to each other, disposed laterally relative to the line between said light sources and equal distance from each of said light sources.

23. The oximeter of claim 7 or 8 encapsulated in biocompatible material, the oximeter constructed and arranged for implantation under the skin of a user for monitoring internal tissue oxygen trends.

8. An oximeter comprising a flexible support member, said support member mounting at least one light source means capable of producing two selected wavelengths and oriented to direct said light to tissue of a user and said support member mounting detector means capable of separately detecting energy at each of said wavelengths scattered by tissue of the user, said support member supporting a barrier member exposed for conformable contact with an exposed surface of the user in position to prevent lateral movement of light from the source means to the detector means, said barrier comprising a member having an edge sized and positioned to indent skin and the flesh of the user thereby to intercept light migrating laterally in the subcutaneous fat layer and prevent such light from reaching said detector means.

9. The oximeter of claim 8 wherein said barrier member is elastomeric, adapted to conform to the contour of the skin of the wearer.

10. The oximeter of claim 9 wherein said flexible support member comprises a molded-elastomeric backing member and said barrier member is integral with said backing member.

11. The oximeter of claim 8, 9 or 10 wherein the member defining said flesh-indenting edge is about 0.5 cm thick in the region that engages the skin.

15. The device of claim 14 wherein said light sources comprise broad spectrum CW light sources.

18. The oximeter of claim 17 wherein said oximeter is associated with means securing it to an appendage of the user and said readout device is constructed to be worn by a user.

24. An oximeter comprising a support mounting a light source and detector means at fixed spacing, and electronic control circuitry for said light source and said detector means, the circuitry disposed upon a miniature semiconductor chip carried by said support member, said oximeter encapsulated in biocompatible water impermeable material, the oximeter constructed and arranged for implantation under the skin of a user for monitoring internal tissue oxygen trends.

25. The method of monitoring the derivative or rate of change of the time based curve representing detected change of tissue oxygen levels and blood volume and employing these rates as a quantitative standard of measurement of tissue oximetry.

26. The method of assisting an aviator or other person engaged in activity that can subject the person to high G-forces including providing to the person a comfortable oximeter sensor suitable to be worn about the head and capable of responding to tissue oxygen level, blood volume of brain tissue on a real time basis, employing said oximeter sensor to monitor oxygen level of brain tissue of the wearer as the wearer engages in said activity, comparing the monitored value to a standard and generating a signal, such as a warning or control signal, in the event the monitored level violates a pre-established standard.

28. The method of monitoring a person suspect of sleep apnea or sudden infant death syndrome including providing to the person a comfortable oximeter sensor capable of automatically responding to oxygen level of the person while permitting the person to sleep, automatically monitoring the output of the oximeter by comparing it to a standard and generating a signal, such as a warning or control signal, in the event the monitored level violates a pre-established standard.

31. The method of monitoring the cerebral tissue oxygen rate of change as a means of triggering alarm to awaken a subject in danger of infarct due to hypoxia.

32. The method of monitoring both tissue oxygen level and blood volume in skin flaps such as are produced either by wound or surgery, as said flaps heal, the separation between the source and the detector being established in relation to the thickness of the skin flap to ensure tissue of the flap per se is being monitored.

37. A helmet into which is molded a tissue oximeter in position to engage the head of the wearer when the helmet is put on, the oximeter being of the NIR type, comprising light source means for transmitting near infrared light into the head, detector means held in spaced position relative to the light source means for receiving light scattered by brain tissue and a barrier disposed to engage the head between the light source means and the detector means to prevent light traveling laterally from the light source means from reaching the detector means.

40. A tissue oximeter comprising a support, a detector fixed to the support and a light source mounted in an adjustable manner to the support to enable selection of the spacing between light source and detector for adjusting the mean depth of tissue to which the oximeter responds.

41. A tissue oximeter in combination with means connected to receive tissue oxygen readings from the oximeter, determine the rate of change of said readings, said rate of change serving as a quantifiable indication of the state of the metabolic process of the tissue.

43. An oximeter disposed on an endoscope, catheter, guidewire or the like for insertion via a body passage to internal tissue, and including means such as an inflatable balloon to press the oximeter sensor against the localized tissue of interest.

50. A method of transcranial examination of brain activity by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the brain comprising

(a) introducing electromagnetic radiation of a selected wavelength into the brain at an input port placed at a selected location on the exterior of the head,

(b) detecting, at a detection port placed at a selected location on the exterior of the head, radiation of said selected wavelength that has migrated in the brain,

(c) causing stimulation of a brain activity while introducing said radiation at said input port and while detecting radiation of said detection port,

(d) processing signals of said detected radiation that has migrated in the brain to create processed data, and

(e) determining a characteristic of said brain activity by correlating said processed data with said caused stimulation of said brain activity.

51. The method of claim 50 wherein said steps of introducing said radiation into the brain and detecting said radiation that has migrated in the brain, while causing stimulation of said brain activity, are repeated at different locations on the exterior of the head, and said step of processing said detected radiation to create processed data is correspondingly repeated.

52. The method of claim 50 or 51 wherein said input port and said output port are located on one of the following:

the frontal bone, parietal bone, temporal bone or occipital bone;

said input port and said output port being separated by a predetermined distance in order to localize said migration of said radiation to a selected region of the brain.

53. The method of claim 52 wherein said predetermined distance is 4 centimeters.

54. The method of claim 50 further comprising

(a) introducing electromagnetic radiation of said selected wavelength into the brain at a second input port placed at a second selected location on the exterior of the head,

(b) detecting, at a second detection port placed at a selected location on the exterior of the head, radiation of said selected wavelength that has migrated in the brain from said second input port to said second detection port,

(c) processing signals of said detected radiation that has migrated in the brain from said second input port to said second detection port to create second processed data, and

(d) determining a characteristic of said brain activity by correlating both first mentioned and said second processed data with said caused stimulation of said brain activity.

55. The method of claim 54 wherein said radiation is simultaneously introduced at said first and second input ports and detected at said first and second detection ports.

56. The method of claim 54 wherein said radiation is first introduced at said first input port and detected at said first detection port, and subsequently said radiation is introduced at said second input port and detected at said second detection port.

58. The method of claim 54 or 57 wherein said first input port and said first output port are located on one parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port are located on the other parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

59. The method of claim 58 wherein said processing comprises comparing electromagnetic radiation detected at said first and second detection ports to create processed data representing a differential signal.

60. The method of claim 54 or 57 wherein said first input port and said first output port are located on one temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port are located on the other temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

61. The method of claim 60 wherein said processing comprises comparing electromagnetic radiation detected at said first and second detection ports to create processed data representing a differential signal.

62. The method of claim 50, 54 or 57 wherein said processing of said detected radiation comprises Fourier transformation.

63. The method of claim 50, 54 or 57 wherein said stimulation is visual stimulation.

64. The method of claim 50, 54 or 57 wherein said stimulation is acoustic stimulation.

65. The method of claim 50, 54 or 57 wherein said stimulation is sensorimotor stimulation.

66. The method of claim 50, 54 or 57 further comprising examining cognitive function of a selected region of the brain based on correlation between said processed data and said caused stimulation of said brain activity.

67. The method of claim 50, 54 or 57 further comprising examining pathological/pathophysiological state of a tissue of a selected region of the brain based on correlation between said processed data and said caused stimulation of said brain activity.

69. The system of claim 68 wherein said processing means adapted to process detected radiation that has migrated in the brain in said migration path between said input port and said output port being separated by a predetermined distance and being located at different locations on the exterior of the head.

70. The system of claim 68 or 69 wherein said input port and said output port are located on one of the following:

the frontal bone, parietal bone, temporal bone or occipital bone;

said input port and said output port being separated by a predetermined distance in order to localize said migration of said radiation to a selected region of the brain.

71. The system of claim 70 wherein said predetermined distance is 4 centimeters.

72. The system of claim 68 further comprising

(a) a second light source adapted to introduce electromagnetic radiation of said selected wavelength into the brain at a second input port placed at a second selected location on the exterior of the head,

(b) a second detector adapted to detect, at a second detection port placed at a selected location on the exterior of the head, radiation of said selected wavelength that has migrated along said migration path in the brain from said second input port to said second detection port, and

(c) processing means adapted to process signals of said detected radiation that has migrated in the brain from said second input port to said second detection port to create second processed data,

wherein said evaluation means determine said characteristic of said brain activity by correlating both first mentioned and said second processed data with said caused stimulation of the brain.

73. The system of claim 72 adapted to introduce simultaneously said radiation at said first and second input ports and detect at said first and second detection ports.

74. The system of claim 72 adapted to introduce said radiation first at said first input port and detected at said first detection port, and subsequently introduce said radiation at said second input port and detected at said second detection port.

76. The system of claim 72 or 75 wherein said first input port and said first output port being located on one parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port being located on the other parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

77. The system of claim 76 wherein said processing means further adapted to compare electromagnetic radiation detected at said first and second detection ports to create processed data representing a differential signal.

78. The system of claim 72 or 75 wherein said first input port and said first output port are located on one temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port are located on the other temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

79. The system of claim 78 wherein said processing means further adapted to compare electromagnetic radiation detected at said first and second detection ports to create processed data representing a differential signal.

80. The system of claim 68, 72 or 75 wherein said processing of said detected radiation comprises Fourier transformation.

81. The system of claim 68, 72 or 75 wherein said stimulation means adapted to cause visual stimulation.

82. The system of claim 68, 72 or 75 wherein said stimulation means adapted to cause acoustic stimulation.

83. The system of claim 68, 72 or 75 wherein said stimulation means adapted to cause sensorimotor stimulation.

84. The system of claim 68, 72 or 75 wherein said evaluation means further adapted to examine cognitive function of a selected region of the brain based on correlation between said processed data and said caused stimulation of said brain activity.

85. The system of claim 68, 72 or 75 wherein said evaluation means further adapted to examine tissue of a selected region of the brain based on correlation between said processed data and said caused stimulation of said brain activity.

57. A method of transcranial examination of brain activity by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the brain comprising

(a) introducing electromagnetic radiation of a selected wavelength into the brain simultaneously at a first input port and at a second input port, said first input port and said second input port being placed at a first selected location and a second selected location on the exterior of the head, respectively,

(b) detecting simultaneously, at a first detection port placed at a selected location on the exterior of the head, radiation that has migrated in the brain from said first input port to said first detection port and, at a second detection port placed at second selected location on the exterior of the head, radiation that has migrated in the brain from said second input port to said second detection port,

(c) causing stimulation of a brain activity while introducing said radiation at said first and second input ports and while detecting radiation at said first and second detection ports,

(d) processing signals of said detected radiation that has migrated in the brain to create processed data, and

(e) determining a characteristic of said brain activity by correlating said processed data to said caused stimulation of said brain activity.

68. A cognition spectrophotometer system for transcranial examination of brain activity by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the brain comprising

(a) a light source adapted to introduce electromagnetic radiation of a selected wavelength into the brain at an input port placed at a selected location on the exterior of the head,

(b) a detector adapted to detect, at a detection port placed at a selected location on the exterior of the head, radiation of said selected wavelength that has migrated in the brain,

(c) stimulation means adapted to cause stimulation of a brain activity while introducing said selected wavelength and while detecting radiation at said detection port,

(d) processing means adapted to process signals of said detected radiation that has migrated in the brain to create processed data, and

(e) evaluation means adapted to determine a characteristic of said brain activity by correlating said processed data with said caused stimulation of said brain activity.

75. A cognition spectrophotometer system for transcranial examination of brain activity by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the brain comprising

(a) a first light source and a second light source adapted to introduce electromagnetic radiation of a selected wavelength into the brain simultaneously at a first input port and at a second input port, said first input port and said second input port being placed at a first selected location and a second selected location on the exterior of the head, respectively,

(b) a first detector and a second detector adapted to detect simultaneously, at a first detection port placed at a selected location on the exterior of the head, radiation that has migrated in the brain from said first input port to said first detection port and, at a second detection port placed at second selected location on the exterior of the head, radiation that has migrated in the brain from said second input port to said second detection port,

(c) stimulation means adapted to cause stimulation of a brain activity while introducing said radiation at said first and second input ports and while detecting radiation at said first and second detection ports,

(d) processing means adapted to process signals of said detected radiation that has migrated in the brain to create processed data, and

(e) evaluation means adapted to determine a characteristic of said brain activity by correlating said processed data to said caused stimulation of said brain activity.

86. The system of claim 75 wherein said first light source and said second light source are tungsten lamps or light emitting diodes.

87. The system of claim 75 wherein said first detector and said second detector are silicon diodes each having an interference filter adapted to detect said radiation of said selected wavelength.

88. The system of claim 75 wherein said first detector and said second detector are light-to-frequency convertors each having an interference filter adapted to detect said radiation of said selected wavelength.

89. The system of claim 88 wherein said processing means comprise

(a) differential counter adapted to register differential signals received from said light-to-frequency convertors,

(b) clocking means adapted to route signals of said detected radiation from said light-to-frequency convertors to said differential counter, and

(c) a frequency-to-voltage converter adapted to convert signals from said differential counter.

90. The system of claim 89 wherein said processing means further comprise a fast Fourier transformer adapted to process differential signal from said frequency-to-voltage converter.

91. The system of claim 90 wherein said evaluation means comprise a storage oscilloscope adapted to analyze the Fourier transformed differential signal of said fast Fourier transformer.

92. The system of claim 89 or 91 wherein said evaluation means further comprises computational means adapted to analyze said differential signal.

94. A method of transcranial examination of a brain tissue by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in the brain comprising

(a) introducing electromagnetic radiation of a selected wavelength into the brain simultaneously at a first input port and at a second input port, said first input port and said second input port being placed at a first selected location and a second selected location on the exterior of the head, respectively,

(b) detecting simultaneously, at a first detection port placed at a selected location on the exterior of the head, radiation that has migrated in the brain from said first input port to said first detection port and, at a second detection port placed at second selected location on the exterior of the head, radiation that has migrated in the brain from said second input port to said second detection port,

(c) processing signals of said radiation detected at said first and second detection port that have migrated in the brain to create first and second processed data, respectively, and

(d) determining a selected property of said brain tissue by correlating said processed first and second data.

95. The method of claim 94 wherein said first input port and said first output port are located on one parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port are located on the other parietal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

96. The method of claim 94 wherein said first input port and said first output port are located on one temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the respective hemisphere of the brain, and said second input port and said second output port are located on the other temporal bone, separated by a predetermined distance, in order to localize migration of said radiation in a selected region of the other hemisphere of the brain.

97. The method of claim 94, 95 or 96 wherein said processing comprises comparing electromagnetic radiation detected at said first and second detection ports to create processed data representing a differential signal.

98. The method of claim 97 wherein said selected property of said brain tissue is a pathophysiological state of said tissue.

99. A method of in vivo examination of a tissue of a human by measuring changes in electromagnetic radiation scattered and absorbed in a migration path in said tissue comprising

(a) introducing electromagnetic radiation of a selected wavelength into the tissue at a first input port placed at a selected location on said human,

(b) detecting, at a first detection port placed at a selected location on said human, radiation of said selected wavelength that has migrated in the first localized tissue of interest from said first input port to said first detection port,

(c) introducing electromagnetic radiation of said selected wavelength into the tissue at a second input port placed at a second selected location on said human,

(d) detecting, at a second detection port placed at a selected location on said human, radiation of said selected wavelength that has migrated in the second localized tissue of interest from said second input port to said second detection port, said first localized tissue of interest having normal physiological properties, said second localized tissue of interest being examined for pathophysiological changes,

(e) processing signals of said detected radiation that has migrated in said first and second localized tissues of interest to create first and second processed data, and

(f) determining pathophysiological changes in said second localized tissue of interest by correlating both said first and said second processed data.

100. The method of claim 99 wherein said radiation is simultaneously introduced at said first and second input ports and detected at said first and second detection ports.

101. The method of claim 99 wherein said radiation is first introduced at said first input port and detected at said first detection port, and subsequently said radiation is introduced at said second input port and detected at said second detection port.