Methods and compositions to reduce scattering of light during therapeutic and diagnostic imaging procedures
View Patent ↗Disclosed are improved methods and compositions for use in light-based in vivo imaging and treatment. The techniques described involve the use of low-scattering, oxygen-carrying blood substitutes in imaging and treatment methods, including OCT imaging. The invention has particular advantages in imaging within the cardiovascular system and highly vascularized or oxygen-dependent tissues.
1. A method for performing optical imaging or light-based treatment of at least a first tissue in an animal, comprising providing into the blood associated with said at least a first tissue a biologically effective amount of a low-scattering, oxygen-carrying blood substitute, wherein the low-scattering, oxygen-carrying blood substitute substantially reduces optical scattering from the blood fraction whilst substantially maintaining tissue oxygenation, and applying an optical imaging or light-based treatment step to said at least a first tissue.
2. The method of claim 1 , wherein said low-scattering, oxygen-carrying blood substitute is a substantially non-particulate hemoglobin solution.
3. The method of claim 2 , wherein said hemoglobin solution is a substantially non-particulate, homogeneous, acellular hemoglobin solution.
4. The method of claim 2 , wherein said hemoglobin solution comprises bovine, porcine, ovine or primate hemoglobin.
5. The method of claim 2 , wherein said hemoglobin solution comprises human hemoglobin.
6. The method of claim 2 , wherein said hemoglobin solution comprises recombinantly produced hemoglobin.
7. The method of claim 2 , wherein said hemoglobin solution comprises crosslinked hemoglobin.
8. The method of claim 2 , wherein said hemoglobin solution comprises polymerized hemoglobin.
9. The method of claim 2 , wherein said hemoglobin solution comprises glutaraldehyde crosslinked, polymerized hemoglobin.
10. The method of claim 2 , wherein said hemoglobin solution comprises surface modified hemoglobin.
11. The method of claim 2 , wherein said hemoglobin solution has a hemoglobin concentration of at least about 70% of the hemoglobin concentration of whole blood.
12. The method of claim 1 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 10%.
13. The method of claim 12 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 5%.
14. The method of claim 13 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 4%.
15. The method of claim 14 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 3%.
16. The method of claim 15 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 2%.
17. The method of claim 16 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue at least to about 1%.
18. The method of claim 1 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue to between 0 and about 10%.
19. The method of claim 18 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue to between 1 and about 5%.
20. The method of claim 1 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue to an amount effective to result in a half maximal or lower scattering coefficient μ s ′ according to the equation μ tot ′=μ a +μ s ′, where μ a is the absorption coefficient and μ tot ′ is the total attenuation coefficient.
21. The method of claim 1 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the hematocrit of the blood associated with said at least a first tissue to an amount effective to result in a scattering coefficient of about half the scattering coefficient for whole blood or less.
22. The method of claim 1 , wherein said low-scattering, oxygen-carrying blood substitute is a solution comprising at least a first oxygen carrier, and wherein the largest species in said solution has a size of about 6 nanometers.
23. The method of claim 1 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the scattering coefficient of the blood associated with said at least a first tissue to about one half of the scattering coefficient of whole blood or less at a sample wavelength of between about 600 nm and about 1500 nm.
24. The method of claim 23 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the scattering coefficient of the blood associated with said at least a first tissue to about one tenth of the scattering coefficient of whole blood or less at a sample wavelength of between about 600 nm and about 1500 nm.
25. The method of claim 23 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the scattering coefficient of the blood associated with said at least a first tissue to about one half of the scattering coefficient of whole blood or less at a sample wavelength of about 600 nm.
26. The method of claim 25 , wherein provision of said low-scattering, oxygen-carrying blood substitute reduces the scattering coefficient of the blood associated with said at least a first tissue to about one tenth of the scattering coefficient of whole blood or less at a sample wavelength of about 600 nm.
27. The method of claim 23 , wherein provision of said low-scattering, oxygen-carrying blood substitute decreases the scattering coefficient of the blood associated with said at least a first tissue to a scattering coefficient of about 0.4 mm −1 or less at about 1310 nm.
28. The method of claim 27 , wherein provision of said low-scattering, oxygen-carrying blood substitute decreases the scattering coefficient of the blood associated with said at least a first tissue to a scattering coefficient of about 0.3 mm −1 or less at about 1310 nm.
29. The method of claim 28 , wherein provision of said low-scattering, oxygen-carrying blood substitute decreases the scattering coefficient of the blood associated with said at least a first tissue to a scattering coefficient of about 0.2 mm −1 at about 1310 nm.
30. The method of claim 1 , wherein said low-scattering, oxygen-carrying blood substitute is a solution comprising at least a first oxygen carrier, and wherein the refractive index of said oxygen carrier is substantially equal to other molecular species in solution.
31. The method of claim 1 , wherein said low-scattering, oxygen-carrying blood substitute has at least about 70% of the oxygen carrying capacity of whole blood.
32. The method of claim 1 , wherein said at least a first tissue is neural tissue.
33. The method of claim 1 , wherein said at least a first tissue is brain tissue.
34. The method of claim 1 , wherein said at least a first tissue is located within a highly perfused organ.
35. The method of claim 34 , wherein said at least a first tissue is located within the kidney, lung, liver, spleen, brain, heart or one of the great vessels.
36. The method of claim 1 , wherein said at least a first tissue is cardiovascular tissue.
37. The method of claim 1 , wherein said at least a first tissue is cardiac tissue.
38. The method of claim 1 , wherein said at least a first tissue is a blood vessel.
39. The method of claim 38 , wherein said optical imaging or treatment step is applied from the lumen of said blood vessel.
40. The method of claim 38 , wherein said blood vessel has or is suspected to have an atherosclerotic plaque or lesion.
41. The method of claim 1 , wherein said at least a first tissue comprises at least two tissue layers, and wherein at least a first of said tissue layers is associated with a substantial blood fraction.
42. The method of claim 41 , wherein said at least a first tissue comprises a plurality of tissue layers, and wherein at least a first of said tissue layers is associated with a substantial blood fraction.
43. The method of claim 1 , wherein said animal has, or is at risk for developing, a cardiac tissue or cardiac valve defect.
44. The method of claim 1 , wherein said animal has suffered, or is at risk for developing, a heart attack.
45. The method of claim 1 , wherein said animal has, or is at risk for developing, an ischemic tissue.
46. The method of claim 1 , wherein said animal has suffered, or is at risk for developing, a stroke.
47. The method of claim 1 , wherein said animal has, or is at risk for developing, a vascularized tumor.
48. The method of claim 1 , wherein said animal is a mouse.
49. The method of claim 1 , wherein said animal is a human subject.
50. A method for optical coherence tomography imaging of a tissue in an animal, which tissue comprises a substantial blood fraction, comprising: (a) introducing into said blood fraction of said tissue an amount of an essentially non-particulate hemoglobin solution effective to substantially reduce optical scattering from said blood fraction whilst substantially maintaining oxygenation in said tissue; and (b) performing optical coherence tomography imaging of said tissue.
51. A method for performing optical imaging or treatment of a tissue in an animal, which tissue comprises a substantial blood fraction, comprising: (a) introducing into said blood fraction of said tissue an amount of a low-scattering, oxygen-carrying blood substitute effective to substantially reduce optical scattering from said blood fraction whilst substantially maintaining oxygenation in said tissue, wherein the low-scattering, oxygen-carrying blood substitute reduces the scattering coefficient of the blood associated with said at least a first tissue to about one half of the scattering coefficient of whole blood or less at a sample wavelength of between about 600 nm and about 1500 nm; and (b) applying an optical imaging or treatment step to said tissue.
52. A method for performing optical imaging of at least a first tissue in an animal, comprising providing into the blood associated with said at least a first tissue a biologically effective amount of a low-scattering, oxygen-carrying blood substitute, wherein the low scattering, oxygen carrying blood substitute includes a size less than about 80 nm to substantially reduce optical scattering, and applying an optical imaging step to said at least a first tissue.
53. A method of generating an image of at least a first vascularized tissue by in vivo diagnostic light imaging, comprising providing into the blood perfusing said vascularized tissue a biologically effective amount of a low-scattering, oxygen-carrying blood substitute, wherein the biologically effective amount results in a reduced scattering coefficient of whole blood to about 66% to 5%, and executing a diagnostic light imaging technique to generate an image of said vascularized tissue.
54. A method for optical coherence tomography imaging of at least a first tissue in an animal, comprising providing into the blood associated with said at least a first tissue a biologically effective amount of a substantially low-scattering between non-particulate hemoglobin solution, and performing optical coherence tomography imaging of said at least a first tissue.