Optical measurement of tissue blood flow, hemodynamics and oxygenation

• US 8,082,015 B2
• Filed: 04/13/2005
• Issued: 12/20/2011
• Est. Priority Date: 04/13/2004
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Yodh, Arjun G., Greenberg, Joel H., Yu, Guoqiang, Durduran, Turgut, Burnett, Mark G., Mohler, Emile R. III, Quon, Harry, Hahn, Stephen M., Detre, John A
• Primary Examiner(s): Jung, Unsu
• Application Number:
  US11/106,390
• Publication Number:
  US 20060063995A1
• Time in Patent Office: 2,442 Days
• Field of Search: 600/310, 600/323, 600/328, 600/344, 600/407, 600473-477, 356/406, 356/477
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/046 in a matrix array
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/02028 Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• CPC Class Codes: A61B 5/0261 using optical means, e.g. infrared light
• CPC Class Codes: A61B 5/14551 for measuring blood gases
• CPC Class Codes: A61B 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 5/4519 Muscles A61B5/389, A61B5/224 take precedence

Abstract

An embodiment of the invention includes a device, system and method for determining the characteristics of deep tissue. The novel method includes measuring blood flow rate and oxygenation characteristics of the tissue, and determining oxygen metabolism of the tissue as a function of the measure blood flow rate and measure oxygenation. The blood flow rate characteristics are measured as a function of light fluctuations caused by the tissue, while the oxygenation characteristics are measured as a function of transmission of light through the tissue with respect to the wavelength of light. The tissue may be layered tissue, for example, a portion of a brain. The tissue characteristics may be measured during times of varying levels of exercise intensity.

Claims

1. A method for determining one or more characteristics of tissue of a subject, the subject having a surface exposed to at least one light source, the method comprising:

measuring a motion of moving scattering particles in the tissue,

wherein the motion of the moving scattering particles is derived at least in part from light field fluctuations,

the light field fluctuations measured, at least in part, by a light temporal autocorrelation function,

the light field fluctuations caused, at least in part, by the moving scattering particles in the tissue and transmission of light through the tissue, the light produced by the least one light source;

measuring blood oxygenation, oxy and deoxy-hemoglobin characteristics, hemodynamic characteristics, and scattering characteristics of the tissue,

wherein the blood oxygenation, oxy and deoxy-hemoglobin characteristics, hemodynamic characteristics, and scattering characteristics are derived, at least in part, from the transmission of light through the tissue with respect to a wavelength of light,

the oxy and deoxy-hemoglobin characteristics being further derived from absorption effects and scattering effects of the tissue on the transmitted light;

determining blood flow rate characteristics based at least in part on collected optical data, the collected optical data based, at least in part, on the motion of the moving scattering particles, the absorption effects of the tissue, and the scattering effects of the tissue; and

determining oxygen metabolism of the tissue and changes of the tissue based at least in part on the blood flow rate characteristics and the oxy and deoxy-hemoglobin characteristics,

at least a portion of the tissue being at least one centimeter beneath the surface.

2. The method of claim 1, wherein the blood oxygenation and hemoglobin characteristics are further derived as a function of a position of a source detector.

3. The method of claim 2, wherein, the source detector and light source are separated by at least about 2 centimeters.

4. The method of claim 1, wherein the tissue is a portion of at least one of the following:

brain, muscle, breast.

5. The method of claim 1, wherein the tissue is a portion of a tumor bearing organ including at least one of the following:

head, neck, prostate, breast, or brain.

6. The method of claim 1, wherein the tissue is at least one of the following:

layered or heterogeneous.

7. The method of claim 1, wherein the tissue characteristics are measured during exercise.

8. The method of claim 1, wherein the tissue characteristics are measured during functional activation.

9. The method of claim 1, wherein the tissue characteristics are measured during a presence of tissue damage due to stroke.

10. The method of claim 1, wherein the tissue characteristics are measured during a presence of tissue damage due to trauma.

11. The method of claim 1, wherein the tissue characteristics are measured during a presence of tissue damage due to cardiovascular disease.

12. The method of claim 1, further comprising determining a velocity of a blood cell in the tissue.

13. The method of claim 1, further comprising determining a motion of cell organelles in the tissue.

14. The method of claim 1, further comprising determining fluctuations of cell organelles in the tissue.

15. The method of claim 1, wherein the blood flow rate and the oxygenation are measured simultaneously.

16. The method of claim 1, further comprising monitoring peripheral vascular disease.

17. The method of claim 1, further comprising monitoring therapeutic interventions to cancers in organs.

18. The method of claim 1, further comprising monitoring effects of cardiovascular disease on muscles.

19. The method of claim 1, further comprising monitoring effects of cerebrovascular disease on brain well-being and function.

20. The method of claim 1, further comprising determining an efficacy of exercise rehabilitation.

21. The method of claim 1, further comprising determining an efficacy of cancer therapy.

22. The method of claim 1, further comprising determining an efficacy of tumor treatment and therapy.

23. The method of claim 1, further comprising monitoring peripheral vascular disease.

24. The method of claim 1, further comprising determining efficacy of a drug used to facilitate blood flow.

25. The method of claim 1, further comprising determining efficacy of a drug used to treat cancers during photodynamic therapy.

26. The method of claim 1, wherein the tissue is human.

27. The method of claim 1, wherein the tissue is animal.

28. The method of claim 1, wherein the measurements are taken without a probe penetrating the subject'"'"'s scalp and skull.

29. The method of claim 1, wherein the measurements are taken non-invasively.

30. A device for analyzing tissue, comprising:

a first light source configured to apply a light to the tissue;

at least one light detector, the at least one light detector configured to detect at least a quantity of light transmitted through the tissue and light field fluctuations caused, at least in part, by moving scattering particles in the tissue; and

a computer processor in communication with the at least one light detector, the computer processor being configured to;

determine a motion of the moving scattering particles in the tissue, the motion of the moving scattering particles being derived at least in part from the light field fluctuations, the light field fluctuations measured, at least in part, by a light temporal autocorrelation function;

determine blood oxygenation, oxy and deoxy-hemoglobin characteristics, hemodynamic characteristics, and scattering characteristics of the tissue, the blood oxygenation, oxy and deoxy-hemoglobin characteristics, hemodynamic characteristics, and scattering characteristics being derived, at least in part, from transmission of light through the tissue with respect to a wavelength of the light, the oxy and deoxy-hemoglobin characteristics being further derived from absorption effects and scattering effects of the tissue on the transmitted light;

determine blood flow rate characteristics based at least in part on collected optical data, the collected optical data based, at least in part, on the motion of the moving scattering particles, the absorption effects of the tissue, and the scattering effects of the tissue; and

determine oxygen metabolism of the tissue and changes of the tissue based at least in part on the blood flow rate characteristics and the oxy and deoxy-hemoglobin characteristics, at least a portion of the tissue being at least about one centimeter beneath the surface.

31. The device of claim 30, further comprising an optical switch that shares light source positions.

32. The device of claim 30, further comprising an electrical switch that shares more than one light detector.

33. The device of claim 30, further comprising at least one of the following:

photodiodes, avalanche photodiodes, photomultiplier tubes, and CCD camera.

34. The device of claim 30, wherein a fast CCD camera or photomultiplier is used as a detector.

35. The device of claim 30, further comprising a computer having a computer-readable medium with computer-executable instructions, wherein the computer-executable instructions calculate a correlation function.

36. The device of claim 30, further comprising a component to measure flow of externally injected microspheres through vasculature.

37. The device of claim 30, further comprising at least one other light detector.

38. The device of claim 30, wherein blood metabolism is measured using a bulk overall value technique.

39. The device of claim 30, wherein the oxygen metabolism is determined at one or more locations.

40. The device of claim 30, wherein the oxygen metabolism is determined as two dimensional images.

41. The device of claim 30, wherein the oxygen metabolism is determined as three dimensional images.

42. The device of claim 30, wherein the light source and light detector are separated by at least about 2 cm.