Metabolism monitoring of body organs

• US 6,738,653 B1
• Filed: 04/11/2000
• Issued: 05/18/2004
• Est. Priority Date: 04/12/1999
• Status: Expired due to Term

• Current Assignee: The State of Israel Atomic Energy Commission Soreq Nuclear Research/Center
• Original Assignee: The State of Israel Atomic Energy Commission Soreq Nuclear Research/Center
• Inventors: Kotler, Zvi, Lev, Aner, Sfez, Bruno Gad
• Primary Examiner(s): Winakur, Eric F.
• Assistant Examiner(s): KREMER, MATTHEW J
• Application Number:
  US09/547,821
• Time in Patent Office: 1,498 Days
• Field of Search: 600/309-310, 600/315-316, 600/322-328, 600/330, 600/336, 600/473-476, 600/320, 600/340
• US Class Current: 600/322
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 8/0808 for diagnosis of the brain
• CPC Class Codes: G01S 15/8968 using acoustical modulation of a light beam acousto-optical light control devices G02F1/11, G02F1/33

Abstract

Method and apparatus for determining the oxygenation level of hemoglobin in a probed region of the human body. A probed region of the body is irradiated with diffuse light, the frequency of which is shifted with ultrasound focused at the probed region. The relation between the two states of the oxygenation of the hemoglobin is determined by the light absorption at the focal region of the ultrasound. The blood volume may be monitored by irradiating the probed region with light at the isosbestic point.

Claims

1. A method for determining a degree of oxygenation of hemoglobin in probed regions of a human body, which comprises the steps of:

successively selecting a plurality of probed regions and for each

(a) irradiating said probed region with diffuse near-infrared laser light;

(b) generating at least one ultrasound wave, chosen from among continuous, pulse or burst waves;

(c) focusing said ultrasound wave in at least a focus region of said probed region, to modulate and frequency-shift said light in said probed region;

(d) detecting said light, modulated by said ultrasound wave, emerging from said focus region;

(e) determining a change in the absorption of said modulated light caused by local changes in said probed region; and

(f) calculating from said change in the absorption the change in the degree of hemoglobin oxygenation in the probed region.

2. A method according to claim 1, further comprising monitoring blood volume in said probed regions by irradiating said probed regions with light at an isosbestic point at which oxyhemoglobin and deoxyhemoglobin have equal absorption of said light modulated by said ultrasound wave.

3. A method according to claim 1, wherein the light has a wavelength in the 690 to 900 nm range.

4. A method according to claim 1, wherein the irradiation is carried out with light having more than one wavelength.

5. A method according to claim 1, wherein the irradiation is carried out with light having at least two wavelengths, one below and one above an isosbestic point.

6. A method according to claim 1, further comprising detecting the light not modulated by the ultrasound wave emerging from the probed region together with the light modulated by the ultrasound wave.

7. A method according to claim 1, wherein the change in the absorption of the ultrasound modulated light in the probed region, due to changes in the oxygenation state of the hemoglobin, is represented by an analog signal, which method further comprises transforming said analog signal to a digital signal, to be processed.

8. A method according to claim 7 wherein said digital signal is visualized.

9. A method according to claim 1, wherein said probed regions are part of the brain of a human body.

10. A method according to claim 1, wherein the at least one ultrasound wave has a frequency in a range from 0.2 to 2 MHz.

11. A method according to claim 1, wherein the probed regions are not a part of the brain and a maximum ultrasound frequency is in a range from 8 to 16 MHz.

12. A method according to claim 1, wherein the light modulated by the ultrasound is expressed by a heterodyne signal created by a technique selected from among detection modulation and source modulation.

13. A method according to claim 1, wherein the light modulated by the ultrasound, emerging from the probed regions is detected by a technique chosen from among time sampling and lock-in CCD technique.

14. A method according to claim 1, wherein the change in the absorption of the said modulated light caused by local change in said probed region is determined by determining intensities of said light modulated by said ultrasound and of light not modulated by said ultrasound and calculating their ratio.

15. A method according to claim 1, wherein the change in the absorption of said modulated light caused by local changes in said probed region is determined by determining the intensity of said light at ω

_L and of said light at ω

_L+Ω

_us, wherein ω

_L is the frequency of the irradiating light and Ω

_us is the frequency of the modulating ultrasound.

16. A method according to claim 1, wherein said at least one ultrasound wave has an intensity chosen so as to obtain a 2Ω

_us shift in frequency of said light at the focal region, while obtaining Ω

_us shift in frequency outside said focal region.

17. Apparatus for determining the oxygenation level of hemoglobin in a probed region of a human body, which comprises:

at least one light generator;

optical fiber bundles and coupling devices optically connecting said generator to the part of the body comprising said probed region;

at least a transducer for generating an ultrasound wave and a focus of said ultrasound wave in said probed region;

optical fibers which collect light that has passed through the probed region and through said focus of said ultrasound wave and transmit it to at least one receiving instrument, and means for elaborating the signals generated by said receiving instrument, said apparatus further comprising a beam splitter, a camera, a discriminator and a liquid crystal valve situated in front of said at least one receiving instrument, in order to increase signal to noise ratio.

18. Apparatus according to claim 17, wherein the receiving instrument is a detector array.

19. Apparatus according to claim 18, wherein the detector array is chosen from among CCD cameras, photomultipliers, or diode detectors.

20. Apparatus according to claim 17, wherein the means for elaborating the signals comprise a digital signal processor and a signal processor and visualizing apparatus.

21. Apparatus according to claim 17, for examining a brain of the human body, wherein the optical fibers are adapted to be directly set on the head at a plurality of positions and the ultrasound wave is generated and focused by a transducer when tightly pressed against the skull.

22. Apparatus according to claim 17, for examining a brain of the human body, wherein the optical fibres are adapted to be directly set on the head at a plurality of positions and the ultrasound wave is generated and focused by a plurality of transducers adapted to be spread over a large region of the skull, arranged so that the ultrasonic waves of each of the transducers are focused in the same region on the brain.

23. Apparatus according to claim 17, wherein the transducers generate ultrasound waves that are phase-arrayed to produce a strong focus in the brain.

24. Apparatus according to claim 17, comprising a plurality of light generators and of detectors, disposed so as to remove any possible shadowing of a part of a probed region on another probed region.

25. A method for determining a degree of oxygenation of hemoglobin in a probed region of a human body, which comprises the steps of:

(a) irradiating a probed region of the human brain with diffuse near-infrared laser light;

(b) generating at least one ultrasound wave, chosen from among continuous, pulse or burst waves;

(c) focusing said ultrasound wave in at least a focus region of said probed region, to modulate and frequency-shift said light in said probed region;

(d) detecting said light, modulated by said ultrasound wave, emerging from said focus region;

(e) determining a change in the absorption of said modulated light caused by local changes in said probed region; and

(f) calculating from said change in the absorption the change in the degree of hemoglobin oxygenation in said probed region.

26. A method according to claim 25, further comprising monitoring blood volume in said probed region by irradiating said probed region with light at an isosbestic point at which oxyhemoglobin and deoxyhemoglobin have equal absorption of said light modulated by said ultrasound wave.

27. A method according to claim 25, wherein said light has a wavelength in the range of 690 to 900 nm.

28. A method according to claim 25, wherein said irradiation is carried out with light having more than one wavelength.

29. A method according to claim 25, wherein the irradiation is carried out with light having at least two wavelengths, one below and one above an isosbestic point.

30. A method according to claim 25, further comprising:

detecting the light not modulated by the ultrasound wave emerging from the probed region together with the modulated light.

31. A method according to claim 25, wherein the change in the absorption of said ultrasound modulated light in said probed region of the brain, due to changes in oxygenation state of the hemoglobin, is represented by an analog signal.

32. A method according to claim 31, further comprising the step of transferring said analog signal to a digital signal, to be processed.

33. A method according to claim 32, wherein said digital signal is visualized.

34. A method according to claim 25, wherein the at least one ultrasound wave has a frequency in a range from 0.2 to 2 MHz.

35. A method according to claim 25, wherein a maximum ultrasound frequency is in a range from 8 to 16 MHz.

36. A method according to claim 25, wherein the light modulated by the ultrasound is expressed by a heterodyne signal created by a technique selected from among detection modulation and source modulation.

37. A method according to claim 25, wherein said light modulated by the ultrasound wave emerging from the probed region is detected by a technique chosen from time sampling and lock-in CCD technique.

38. A method according to claim 25, wherein the change in the absorption of said modulated light caused by local change in said probed region is determined by determining intensities of said light modulated by said ultrasound and of light not modulated by said ultrasound and calculating their ratio.

39. A method according to claim 25, wherein the change in the absorption of said modulated light caused by local change in said probed region is determined by determining intensity of said light at ω

_L and of said light at ω

_L+Ω

_us, wherein Ω

_L is the frequency of the irradiating light and Ω

_us is the frequency of the modulating ultrasound.

40. A method according to claim 25, wherein said at least one ultrasound wave has an intensity chosen so as to obtain a 2Ω

_us shift in frequency of said light at the focal region, while obtaining Ω

_us shift in frequency outside said focal region.

41. A method for determining a degree of oxygenation of hemoglobin in a probed region of a human body, which comprises the steps of:

(a) irradiating the probed region with diffuse near-infrared laser light;

(b) generating at least one ultrasound wave, chosen from among continuous, pulse or burst waves;

(c) focusing said ultrasound wave in at least a focus region of said probed region, to modulate and frequency-shift said light in said probed region;

(d) detecting said light, modulated by said ultrasound wave, emerging from said focus region;

(e) determining the change in the absorption of said modulated light caused by local changes in said probed region; and

(f) calculating from said change in the absorption the change in the degree of hemoglobin oxygenation in said probed region;

wherein the light modulated by said ultrasound emerging from the said probed region is detected by a technique chosen from among time sampling and lock-in CCD technique.

42. A method according to claim 41, further comprising monitoring blood volume in said probed region by irradiating said probed region with light at an isosbestic point at which oxyhemoglobin and deoxyhemoglobin have equal absorption of said light modulated by said ultrasound wave.

43. A method according to claim 41, wherein said light has a wavelength in the range of 690 to 900 nm.

44. A method according to claim 41, wherein said irradiation is carried out with light having more than one wavelength.

45. A method according to claim 41, wherein the irradiation is carried out with light having at least two wavelengths, one below and one above an isosbestic point.

46. A method according to claim 41, further comprising:

detecting light not modulated by the ultrasound wave emerging from the probed region together with the modulated light.

47. A method according to claim 41, wherein the change in the absorption of said ultrasound modulated light in said probed region, due to changes in oxygenation state of the hemoglobin, is represented by an analog signal.

48. A method according to claim 47, further comprising the step of transferring said analog signal to a digital signal, to be processed.

49. A method according to claim 48, wherein said digital signal is visualized.

50. A method according to claim 41, wherein the at least one ultrasound wave has a frequency in a range from 0.2 to 2 MHz.

51. A method according to claim 41, wherein a maximum ultrasound frequency is in a range from 8 to 16 MHz.

52. A method according to claim 41, wherein the light modulated by the ultrasound is expressed by a heterodyne signal created by a technique selected from among detection modulation and source modulation.

53. A method according to claim 41, wherein the change in the absorption of said modulated light caused by local change in said probed region is determined by determining intensities of said light modulated by said ultrasound and of light not modulated by said ultrasound and calculating their ratio.

54. A method according to claim 41, wherein the change in the absorption of said modulated light caused by local change in said probed region is determined by determining intensity of said light at ω

_L and of said light at ω

_L+Ω

_us, wherein ω

_L is the frequency of the irradiating light and Ω

_us is the frequency of the modulating ultrasound.

55. A method according to claim 41, wherein said at least one ultrasound wave has an intensity chosen so as to obtain a 2Ω

_us shift in frequency of said light at the focal region, while obtaining Ω

_us shift in frequency outside said focal region.