Detection of stroke events using diffuse optical tomagraphy

• US 6,577,884 B1
• Filed: 06/19/2000
• Issued: 06/10/2003
• Est. Priority Date: 06/19/2000
• Status: Expired due to Fees

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Boas, David Alan
• Primary Examiner(s): SHAW, SHAWNA JEANNINE
• Application Number:
  US09/598,422
• Time in Patent Office: 1,086 Days
• Field of Search: 600/473, 600/475, 600/476, 600/477, 600/322, 600/323, 600/310, 356/39-41, 356/42
• US Class Current: 600/310
• CPC Class Codes: A61B 5/0042 for the brain
• CPC Class Codes: A61B 5/0073 by tomography, i.e. reconstruction of 3D images from 2D projections A61B5/0066 takes precedence
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance

Abstract

The invention relates to a method of using diffuse optical tomography and oxygen in a stroke patient, or a patient suspected of having a stroke, to detect ischemic events or bleeds in the brain.

Claims

1. A method of detecting an ischemic event in a brain in a subject, the method comprising

administering an oxygen bolus into the bloodstream of the subject;

directing light into the brain of the subject;

detecting light emitted from the brain over time at a detection location, wherein the oxygen bolus is present in the brain for at least a portion of the detection time, and the light emitted from the brain in the presence of the oxygen bolus is different from the light emitted from the brain in the absence of the oxygen bolus, the magnitude of the difference corresponding to a difference in concentration of total oxygen;

establishing a reference time period corresponding to a time a peak concentration of the oxygen bolus takes to reach the detection location in a normal brain;

determining a subject time period corresponding to a time a peak concentration of the oxygen bolus takes to reach the detection location in the subject; and

comparing the subject time period with the reference time period, wherein a subject time period 1 or more seconds longer than the reference time period indicates an ischemic event in the brain.

2. The method of claim 1, wherein the oxygen is administered to the subject by inhalation of an atmosphere having above about 50% oxygen by volume.

3. The method of claim 1, wherein the difference is in the amplitude of light.

4. The method of claim 1, wherein the subject is a mammal.

5. The method of claim 4, wherein the mammal is a human.

6. The method of claim 1, comprising directing light into the brain through the scalp from a plurality of light sources and detecting light emitted from the brain using a plurality of photodetectors.

7. The method of claim 1, wherein the light is emitted and detected using a system comprising:

at least two optical sources which during operation emit light into the brain at spatially separated locations;

at least two optical detectors positioned to receive light emitted from the brain at spatially separated locations in response to the light emitted from the sources, wherein signal g(i,j) produced by a j^th detector in response to optical radiation from an i^th source can be expressed as g(i,j)=SⁱD^jf(i,j), where f(i,j) depends only on optical properties of the head of the subject, Sⁱ is a coupling coefficient for the i^th source, and D^j is a coupling coefficient for the j^th detector; and

an analyzer which during operation calculates a value of product S^lD^k for at least one of the source-detector pairs based on signals produced by the detectors and simulated values of f(i,j) corresponding to a model of optical properties of the head of the subject, where S^l is a coupling coefficient for an lth source and D^k is a coupling coefficient for a kth detector.

8. The method of claim 1, wherein light is directed by at least two optical sources, light is detected by at least two optical detectors, the sources couple light into the brain at spatially separated locations, and the detectors are positioned to receive light emitted from the brain at spatially separated locations and generate signals in response to the light from the sources;

the method further comprising

providing the signals generated by the detectors, wherein signal g(i,j) generated by a j^th detector in response to optical radiation from an i^th source can be expressed as g(i,j)=SⁱD^jf(i,j), where f(i,j) depends only on optical properties of the head of the subject, Sⁱ is a coupling coefficient for the i^th source, and D^j is a coupling coefficient for the j^th detector; and

calculating a value of product S^lD^k for at least one of the source-detector pairs based on signals generated by the detectors and simulated values of f(i,j) corresponding to a model of optical properties of the head of the subject, where S^l is a coupling coefficient for an lth source and D^k is a coupling coefficient for a kth detector.

9. A method of detecting an ischemic event in a deep portion of a brain, the method comprising detecting an ischemic event in the brain of a subject using the method of claim 1, wherein a subject time period of 2 or more seconds longer than the reference time period indicates an ischemic event in a deep portion of the brain.

10. A method of detecting an ischemic event in a brain in a subject, the method comprising

administering an oxygen bolus into the bloodstream of the subject;

directing light into the brain of the subject;

detecting light emitted from the brain over time at a detection location, wherein the oxygen bolus is present in the brain for at least a portion of the detection time, and the light emitted from the brain in the presence of the oxygen bolus is different from the light emitted from the brain in the absence of the oxygen bolus, the magnitude of the difference corresponding to a difference in concentration of total oxygen;

establishing a peak reference concentration of the oxygen bolus administered to a subject with a normal brain at the detection location;

determining a peak subject concentration of the oxygen bolus at the detection location; and

comparing the peak subject concentration with the peak reference concentration, wherein a peak subject concentration below the peak reference concentration indicates an ischemic event in the brain.

11. The method of claim 10, wherein the oxygen is administered to the subject by inhalation of an atmosphere having above about 50% oxygen by volume.

12. The method of claim 10, wherein the difference is in the amplitude of light.

13. The method of claim 10, wherein the subject is a mammal.

14. The method of claim 13, wherein the mammal is a human.

15. The method of claim 10, comprising directing light into the brain through the scalp from a plurality of light sources and detecting light emitted from the brain using a plurality of photodetectors.

16. A method of detecting an ischemic event in a deep portion of a brain, the method comprising detecting an ischemic event in the brain of a subject using the method of claim 10, wherein a peak subject concentration between 100% and 50% of a peak reference concentration indicates an ischemic event in a deep portion of the brain.

17. A method of detecting an ischemic event in a deep portion of a brain, the method comprising detecting an ischemic event in the brain of a subject using the method of claim 10, wherein a peak subject concentration below a peak reference concentration but at least 50% of the peak reference concentration indicates an ischemic event in a deep portion of the brain.

18. A method of detecting an ischemic event in a brain in a subject, the method comprising

administering an oxygen bolus into the bloodstream of the subject;

directing light into the brain of the subject;

detecting light emitted from the brain over time at a detection location, wherein the oxygen bolus is present in the brain for at least a portion of the detection time, and the light emitted from the brain in the presence of oxygen bolus is different from the light emitted from the brain in the absence of the oxygen bolus, the magnitude of the difference corresponding to a difference in concentration of total oxygen;

establishing a reference time period corresponding to a time for a concentration of the oxygen bolus to vary from a threshold concentration to a peak concentration and back to the threshold concentration at the detection location in a normal brain;

determining a subject time period corresponding to a time for a concentration of the oxygen bolus to vary from a threshold concentration to a peak concentration and back to the threshold concentration at the detection location; and

comparing the subject time period with the reference time period, wherein a subject time period longer than the reference time period indicates an ischemic event in the brain.

19. The method of claim 18, wherein the oxygen is administered to the subject by inhalation of an atmosphere having above about 50% oxygen by volume.

20. The method of claim 18, wherein the difference is in the amplitude of light.

21. The method of claim 18, wherein the subject is a mammal.

22. The method of claim 21, wherein the mammal is a human.

23. The method of claim 18, comprising directing light into the brain through the scalp from a plurality of light sources and detecting light emitted from the brain using a plurality of photodetectors.

24. The method of claim 18, wherein the threshold concentration is about 85-95% oxygen saturation.

25. A method of detecting an ischemic event in a brain in a subject, the method comprising

administering an oxygen bolus into the bloodstream of a subject;

directing light into the brain of the subject;

detecting light emitted from the brain over time at a detection location, wherein the oxygen bolus is present in the brain for at least a portion of the detection time, and the light emitted from the brain in the presence of the oxygen bolus is different from the light emitted from the brain in the absence of the oxygen bolus, the magnitude of the difference corresponding to a difference in concentration of total oxygen;

establishing a reference map of cortical blood flow in a normal brain;

obtaining a subject map of cortical blood flow in the subject; and

comparing the reference map with the subject map, wherein a continuous region of decreased blood flow in the subject map compared to the reference map indicates an ischemic event in the brain.

26. The method of claim 25, wherein the oxygen is administered to the subject by inhalation of an atmosphere having above about 50% oxygen by volume.

27. The method of claim 25, wherein the difference is in the amplitude of light.

28. The method of claim 25, wherein subject is a mammal.

29. The method of claim 28, wherein the mammal is a human.

30. The method of claim 25, comprising directing light into the brain through the scalp from a plurality of light sources and detecting light emitted from the brain using a plurality of photodetectors.

31. The method of claim 25, further comprising

comparing the position of the region of decreased blood flow with a map of known brain vasculature; and

extrapolating the position of the ischemic event in the brain of the subject.

32. A method of detecting an ischemic event in a brain in a subject, the method comprising

administering an oxygen bolus into the bloodstream of the subject;

directing light into the brain of the subject;

detecting light emitted from the brain over time at a detection location, wherein the oxygen bolus is present in the brain for at least a portion of the detection time, and the light emitted from the brain in the presence of the oxygen bolus is different from the light emitted from the brain in the absence of the oxygen bolus, the magnitude of the difference corresponding to the difference in concentration of total oxygen;

establishing (1) a first reference time period corresponding to a time a peak concentration of the oxygen bolus takes to reach the detection location in a normal brain, (2) a peak reference concentration for the oxygen bolus administered to a subject with a normal brain at the detection location, and (3) a second reference time period corresponding to a time for the concentration of the oxygen bolus to vary from a threshold concentration to a peak concentration and back to the threshold concentration at the detection location in a normal brain;

determining (1) a first subject time period corresponding to the time a peak concentration of the oxygen bolus takes to reach the detection location in the subject, (2) a peak subject concentration of the oxygen bolus at the detection location, and (3) a second subject time period corresponding to the time for the concentration of oxygen to vary from the threshold concentration to a peak concentration and back to the threshold concentration at the detection location; and

comparing the first subject time period with the first reference time period, the peak subject concentration with the peak reference concentration, and the second subject time period with the second reference time period;

wherein a first subject time period 1 or more seconds longer than the reference time period, a peak subject concentration below the peak reference concentration, and a second subject time period longer than the second reference time period together indicate an ischemic event in the brain.

33. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a subject time period corresponding to a time a peak concentration of an oxygen bolus takes to reach a detection location in the brain of a subject with (2) a reference time period corresponding to a time a peak concentration of the oxygen bolus takes to reach the detection location in a normal brain, wherein a subject time period 1 or more seconds longer than the reference time period indicates an ischemic event in the brain.

34. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a peak subject concentration of an oxygen bolus at a detection location in the brain of a subject with (2) a peak reference concentration of the oxygen bolus administered to a subject with a normal brain at the detection location, wherein a peak subject concentration below the peak reference concentration indicates an ischemic event in a deep portion of the brain.

35. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a subject time period required for a concentration of an oxygen bolus to vary from a threshold concentration to a peak concentration and back to the threshold concentration at a detection location in the brain of a subject with (2) a reference time period corresponding to the time for a concentration of the oxygen bolus to vary from the threshold concentration to a peak concentration and back to threshold concentration at the detection location in a normal brain, wherein a subject time period longer than the reference time period indicates an ischemic event in the brain.

36. A method of detecting a brain bleed in a subject, the method comprising

administering oxygen into the bloodstream of the subject;

directing light from a light source into the brain of the subject;

detecting light emitted from the brain while the oxygen is present in a portion of the brain, the light emitted from the brain in the presence of the oxygen being different from the light emitted from the brain in the absence of the oxygen, the magnitude of the difference corresponding to a difference in concentration of total oxygen, wherein the detecting step is performed while the oxygen is detectable in the blood circulation of the subject; and

determining the concentration of the oxygen in the portion of the brain, wherein a region of the portion with a lower concentration of the oxygen than an adjacent region of the portion indicates a brain bleed.

37. The method of claim 36, wherein the subject is a mammal.

38. The method of claim 37, wherein the mammal is a human.

39. The method of claim 36, wherein the difference is in the amplitude of light.

40. A method of detecting a brain bleed in a subject, the method comprising

administering oxygen into the bloodstream of the subject;

directing light from a light source into the brain of the subject;

detecting light emitted from the brain while the oxygen is present in a portion of the brain, the light emitted from the brain in the presence of the oxygen being different from the light emitted from the brain in the absence of the oxygen, the magnitude of the difference corresponding to a difference in concentration of total oxygen, wherein the detecting step is performed after an initial oxygen concentration in the blood circulation of the subject has been reduced; and

determining a concentration of the oxygen in the portion of the brain, wherein a region of the portion with a higher concentration of the oxygen than an adjacent region of the portion indicates a brain bleed.

41. The method of claim 40, wherein the subject is a mammal.

42. The method of claim 41, wherein the mammal is a human.

43. The method of claim 40, wherein the difference is in the amplitude of light.