Detection of stroke events using diffuse optical tomography

• US 6,516,214 B1
• Filed: 01/25/2000
• Issued: 02/04/2003
• Est. Priority Date: 01/24/2000
• 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): Lateef, Marvin M.
• Assistant Examiner(s): Shah, Devaang
• Application Number:
  US09/491,595
• Time in Patent Office: 1,106 Days
• Field of Search: 600/477, 600/473, 600/476, 600/431, 600/310
• US Class Current: 600/431
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/046 in a matrix array
• 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 5/0275 using tracers, e.g. dye dilution
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/6814 Head

Abstract

The invention relates to a method of using diffuse optical tomography and a blood-borne dye 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 a dye 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 dye 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 dye is different from the light emitted from the brain in the absence of the dye, the magnitude of the difference corresponding to the concentration of the dye;

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

determining a subject time period corresponding to the time a peak concentration of the dye 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 dye is indocyanine green.

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 a sample at spatially separated locations;

at least two optical detectors positioned to receive light emitted from the sample at spatially separated locations in response to the light emitted from the sources, wherein the signal g(i,j) produced by the j^th detector in response to the optical radiation from the i^th source can be expressed as g(i,j)=SⁱD^jf(i,j), where f(i,j) depends only on the 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 the value of the product S^lD^k for at least one of the source-detector pairs based on the signals produced by the detectors and simulated values of f(i,j) corresponding to a model of the optical properties of the sample.

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

calculating the value of the product S^lD^k for at least one of the source-detector pairs based on the signals generated by the detectors and simulated values of f(i,j) corresponding to a model of the optical properties of the brain.

45. 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.

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

administering a dye 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 dye 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 dye is different from the light emitted from the brain in the absence of the dye, the magnitude of the difference corresponding to the concentration of the dye;

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

determining a peak subject concentration of the dye 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.

10. The method of claim 9, wherein the dye is indocyanine green.

11. The method of claim 9, wherein the difference is in the amplitude of light.

12. The method of claim 9, wherein the subject is a mammal.

13. The method of claim 12, wherein the mammal is a human.

14. The method of claim 9, 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.

46. 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 9, wherein a peak subject concentration between 100% and 50% of the peak reference concentration indicates an ischemic event in a deep portion of the brain.

47. 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 9, wherein a peak subject concentration below the peak reference concentration but at least 50% of the peak reference concentration indicates an ischemic event in a deep portion of the brain.

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

administering a dye 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 dye 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 dye is different from the light emitted from the brain in the absence of the dye, the magnitude of the difference corresponding to the concentration of the dye;

establishing a reference time period corresponding to the time for the concentration of a dye 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 the time for the concentration of the dye to vary from the 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.

16. The method of claim 15, wherein the dye is indocyanine green.

17. The method of claim 15, wherein the difference is in the amplitude of light.

18. The method of claim 15, wherein the subject is a mammal.

19. The method of claim 18, wherein the mammal is a human.

20. The method of claim 15, 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.

21. The method of claim 15, wherein the threshold concentration is 10% on a volume basis.

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

administering a dye 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 dye 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 dye is different from the light emitted from the brain in the absence of the dye, the magnitude of the difference corresponding to the concentration of the dye;

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.

23. The method of claim 22, wherein the dye is indocyanine green.

24. The method of claim 22, wherein the difference is in the amplitude of light.

25. The method of claim 22, wherein subject is a mammal.

26. The method of claim 25, wherein the mammal is a human.

27. The method of claim 22, 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.

48. 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 22, wherein a continuous region of decreased blood flow in the subject map, compared to the reference map, of at least 20 mm at the longest diameter, indicates an ischemic event in the deep portion of the brain.

49. The method of claim 22, 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.

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

administering a dye 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 dye 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 dye is different from the light emitted from the brain in the absence of the dye, the magnitude of the difference corresponding to the concentration of the dye;

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

29. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a subject time period corresponding to the time a peak concentration of a dye bolus takes to reach a detection location on the brain of a subject with (2) a reference time period corresponding to the time a peak concentration of a dye 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.

30. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a peak subject concentration of a dye bolus at a detection location on the brain of the subject with (2) a peak reference concentration of a dye 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 the deep portion of the brain.

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

32. A method of detecting an ischemic event in a brain in a subject, the method comprising comparing (1) a subject map of cortical blood flow in the brain of a subject with (2) a reference map of cortical blood flow in a normal brain, wherein a continuous region of decreased blood flow in the subject map, compared to the reference map, of at least 20 mm at the longest diameter indicates an ischemic event in the brain.

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

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

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

34. The method of claim 33, wherein no detectable dye is present in the region of the portion.

35. The method of claim 33, wherein the dye is indocyanine green.

36. The method of claim 33, wherein the subject is a mammal.

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

38. The method of claim 33, wherein the difference is in the amplitude of light.

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

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

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

40. The method of claim 39, wherein no detectable dye is present in the blood circulation of the subject.

41. The method of claim 39, wherein the dye is indocyanine green.

42. The method of claim 39, wherein the subject is a mammal.

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

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