Method for optically imaging solid tumor tissue

• US 5,699,798 A
• Filed: 06/07/1995
• Issued: 12/23/1997
• Est. Priority Date: 08/10/1990
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Hochman, Daryl, Haglund, Michael M.
• Primary Examiner(s): Jastrzab, Jeffrey R.
• Assistant Examiner(s): SHAW, SHAWNA JEANNINE
• Application Number:
  US08/477,468
• Time in Patent Office: 930 Days
• Field of Search: 128/653.1, 128/664, 128/665, 128/633, 128/654, 348/77, 348/68, 348/164
• US Class Current: 600/420
• 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 5/14553 specially adapted for cerebral tissue
• CPC Class Codes: A61B 90/36 Image-producing devices or illumination devices not otherwise provided for
• CPC Class Codes: G06T 5/50 using two or more images, e.g. averaging or subtraction
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 20/40 relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• CPC Class Codes: G16H 30/20 for handling medical images, e.g. DICOM, HL7 or PACS

Abstract

The present invention provides a method and apparatus for determining the presence of solid tumor tissue, for identifying and mapping the margins of solid tumors during surgical or diagnostic procedures, and for grading and characterizing tumor tissue by detecting changes in the optical properties of an area of interest suspected to contain tumor tissue.

Claims

1. A method for detecting margins and dimensions of tumor tissue in an area of interest, comprising:

(a) illuminating the area of interest with an illumination source emitting electromagnetic radiation (emr) having at least one wavelength which interacts with a dye, the emr having a wavelength of from about 450 nm to about 2500 nm;

(b) detecting one or more optical properties of the area of interest using an optical detector;

(c) acquiring and storing a control data set representing the one or more optical properties detected;

(d) administering the dye to the area of interest;

(e) detecting one or more optical properties of the area of interest subsequent to administration of the dye and acquiring a subsequent data set representing the one or more optical properties detected subsequent to administration of the dye;

(f) comparing the subsequent data set with the control data set to produce a comparison data set; and

(g) identifying changes in the one or more optical properties in the comparison data set and thereby identifying areas of solid tumor tissue, wherein the tumor tissue is characterized by one of different rates of dye uptake and different rates of dye perfusion compared to normal tissue.

2. A method according to claim 1, wherein the dye is selected from the group consisting of indocyanines, fluoresceins, hematoporphyrins, fluoresdamines and combinations thereof.

3. A method according to claim 1, wherein the area of interest is located underneath intact skin and/or bone and the emr is in the infrared region.

4. A method according to claim 1, wherein the illumination source and the optical detector are fixed in position relative to one another.

5. A method according to claim 1, wherein the optical detector is a video camera.

6. A method according to claim 1, additionally comprising amplifying portions of the control data set to enhance the contrast of the comparison data set.

7. A method according to claim 1, additionally comprising identifying data points in the comparison data set having intermediate values that represent optical changes indicative of solid tumor tissue, and mapping the data points having intermediate values to logarithmically or linearly increasing values to enhance the contrast of the comparison data set.

8. A method according to claim 1, additionally comprising compensating for movement in the area of interest by aligning corresponding spatial locations in the control and subsequent data sets to produce the comparison data set.

9. A method according to claim 1, wherein the control data set is a control image, the subsequent data set is a subsequent image, and the comparison data set is a comparison image.

10. A method according to claim 9, wherein the control and subsequent images are obtained as analog video signals and the analog video signals are amplified and spread across a full dynamic range.

11. A method according to claim 9, additionally comprising mapping different pixel values comprising the comparison image to color values to enhance the contrast of the comparison image.

34. A method according to claim 1, wherein the dye is an emr absorbing, phosphorescent or fluorescent material.

35. A method according to claim 34, wherein the dye is conjugated to a targeting molecule.

36. A method according to claim 1, further comprising illuminating the area of interest with a source of uniform illumination.

37. A method according to claim 1, further comprising illuminating the area of interest with a source of non-continuous illumination.

38. A method according to claim 1, further comprising detecting one or more optical properties of the area of interest using an optical detection system external to the area of interest.

39. A method according to claim 1, further comprising detecting one or more optical properties of the area of interest using optical detection components mounted on an invasive or semi-invasive system.

12. A method of grading or characterizing tumor tissue located in an area of interest, comprising:

(a) illuminating the area of interest with an illumination source emitting electromagnetic radiation (emr) having at least one wavelength which interacts with a dye, the emr having a wavelength of from about 450 nm to about 2500 nm;

(b) detecting one or more optical properties of the area of interest using an optical detector;

(c) acquiring and storing a control data set representing the one or more optical properties detected;

(d) administering the dye to the area of interest;

(e) detecting one or more optical properties of the area of interest subsequent to administration of the dye and acquiring a subsequent data set representing the one or more optical properties detected subsequent to administration of the dye;

(f) comparing the subsequent data set with the control data set to produce a comparison data set; and

(g) identifying changes in the one or more optical properties in the comparison data set, wherein different degrees of malignant tumor tissue are characterized by one of different rates of dye uptake and different rates of dye perfusion compared to lower grade malignant tumor tissue and benign tumor tissue.

13. A method according to claim 12, wherein the dye is selected from the group consisting of indocyanines, fluoresceins, hematoporphyrins, fluoresdamines and combinations thereof.

14. A method according to claim 12, wherein the area of interest is located underneath intact skin and/or bone and the emr is in the infrared region.

15. A method according to claim 12, wherein the illumination source and the optical detector are fixed in position relative to one another.

16. A method according to claim 12, wherein the optical detector is a video camera.

17. A method according to claim 12, additionally comprising amplifying portions of the control data set to enhance the contrast of the comparison data set.

18. A method according to claim 12, additionally comprising identifying data points in the comparison data set having intermediate values that represent optical changes indicative of solid tumor tissue, and mapping the data points having intermediate values to logarithmically or linearly increasing values to enhance the contrast of the comparison data set.

19. A method according to claim 12, additionally comprising compensating for movement in the area of interest by aligning corresponding spatial locations in the control and subsequent data sets to produce the comparison data set.

20. A method according to claim 12, wherein the control data set is a control image, the subsequent data set is a subsequent image, and the comparison data set is a comparison image.

21. A method according to claim 20, wherein the control and subsequent images are obtained as analog video signals and the analog video signals are amplified and spread across a full dynamic range.

22. A method according to claim 20, additionally comprising mapping different pixel values comprising the comparison image to color values to enhance the contrast of the comparison image.

23. A method for distinguishing between tumor tissue and non-tumor tissue in an area of interest, comprising:

(a) administering a dye to the area of interest;

(b) illuminating the area of interest with an illumination source emitting electromagnetic radiation (emr) having at least one wavelength which interacts with the dye, the emr having a wavelength of from about 450 nm to about 2500 nm;

(c) detecting one or more optical properties of the area of interest using an optical detector;

(d) acquiring and storing a data set representing the one or more optical properties detected; and

(e) identifying differences in the one or more optical properties within the data set and thereby identifying areas of solid tumor tissue, wherein the solid tumor tissue is characterized by one of different rates of dye uptake and different rates of dye perfusion compared to normal tissue.

24. A method according to claim 23, wherein the dye is selected from the group consisting of indocyanines, fluoresceins, hematoporphyrins, fluoresdamines and combinations thereof.

25. A method according to claim 23, wherein the area of interest is located underneath intact skin and/or bone and the emr is in the infrared region.

26. A method according to claim 23, wherein the illumination source and the optical detector are fixed in position relative to one another.

27. A method according to claim 23, wherein the optical detector is a video camera.

40. A method according to claim 23, wherein the dye is an emr absorbing, phosphorescent or fluorescent material.

41. A method according to claim 40, wherein the dye is conjugated to a targeting molecule.

42. A method according to claim 23, further comprising illuminating the area of interest with a source of uniform illumination.

43. A method according to claim 23, further comprising illuminating the area of interest with a source of non-continuous illumination.

44. A method according to claim 23, further comprising detecting one or more optical properties of the area of interest using an optical detection system external to the area of interest.

45. A method according to claim 23, further comprising detecting one or more optical properties of the area of interest using optical detection components mounted on an invasive or semi-invasive system.

28. A method of grading or characterizing tumor tissue located in an area of interest, comprising:

(a) administering a dye to the area of interest;

(b) illuminating the area of interest with an illumination source emitting electromagnetic radiation (emr) having at least one wavelength which interacts with the dye, the emr having a wavelength of from about 450 nm to about 2500 nm;

(c) detecting one or more optical properties of the area of interest using an optical detector;

(d) acquiring and storing a data set representing the one or more optical properties detected; and

(e) identifying differences in the one or more optical properties within the data set and thereby identifying areas of malignant and lower grade tumor tissue, wherein different degrees of malignant tumor tissue are characterized by one of different rates of dye uptake and different rates of dye perfusion compared to the lower grade malignant tumor tissue and benign tumor tissue.

29. A method according to claim 28, wherein the dye is selected from the group consisting of indocyanines, fluoresceins, hematoporphyrins, fluoresdamines and combinations thereof.

30. A method according to claim 28, wherein the area of interest is located underneath intact skin and/or bone and the emr is in the infrared region.

31. A method according to claim 28, wherein the illumination source and the optical detector are fixed in position relative to one another.

32. A method according to claim 28, wherein the optical detector is a video camera.

33. A method for detecting margins and dimensions of tumor tissue in an area of interest, comprising:

(a) illuminating the area of interest with an illumination source emitting electromagnetic radiation (emr) having at least a first and a second, different, wavelength which interact with a dye, the emr being in the visible or infrared regions;

(b) detecting one or more optical properties of the area of interest for each of the first and second wavelengths of emr using an optical detector;

(c) acquiring and storing a first and a second control data set representing the one or more optical properties detected;

(d) administering the dye to the area of interest;

(e) detecting one or more optical properties of the area of interest for each of the first and second wavelengths of emr subsequent to administration of the dye and acquiring a first and a second subsequent data set representing the one or more optical properties detected subsequent to administration of the dye;

(f) comparing the first subsequent data set with the first control data set and the second subsequent data set with the second control data set to produce a first and a second comparison data set;

(g) obtaining an enhanced comparison data set by rationing the first comparison data set to the second comparison data set; and

(h) identifying changes in the one or more optical properties in the enhanced comparison data set and thereby identifying areas of solid tumor tissue, wherein the solid minor tissue is characterized by one of different rates of dye uptake and different rates of dye perfusion compared to normal tissue.