Method and apparatus for optically imaging solid tumor tissue

• US 6,241,672 B1
• Filed: 12/18/1997
• Issued: 06/05/2001
• Est. Priority Date: 08/10/1990
• Status: Expired due to Fees

• Current Assignee: University of Washington
• Original Assignee: University of Washington
• Inventors: Hochman, Daryl, Haglund, Michael M.
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): SHAW, SHAWNA JEANNINE
• Application Number:
  US08/993,733
• Time in Patent Office: 1,265 Days
• Field of Search: 600/407, 600/473, 600/476, 600/431, 600/475, 600/477, 348/68, 348/77, 348/164, 382/128
• US Class Current: 600/431
• 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 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;

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

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

(d) comparing the subsequent data set with a control data set representing the one or more optical properties of the area of interest prior to administration of the dye to produce a comparison data set; and

(e) distinguishing tumor from non-tumor tissue in the area of interest based on differences in the one or more optical properties evidenced in the comparison data set, the differences in the one or more optical properties “

representing”

different dynamics of dye perfusion in tumor and non-tumor 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 at least one of intact skin and bone and the emr is in the infrared region.

4. A method according to claim 1, step (c), wherein detecting is carried out with a CCD apparatus.

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

6. 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.

7. A method according to claim 6, 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.

8. A method according to claim 6, additionally comprising mapping different pixel values comprising the comparison image to color values to enhance the contrast of the comparison image.

9. A method according to claim 1, wherein the optical property detected is selected from the group consisting of:

reflection;

refraction;

diffraction;

absorption;

scattering;

birefringence;

refractive index; and

Kerr effect.

10. A method according to claim 1, wherein the comparison data set is displayed in a graphical format.

11. A method according to claim 1, wherein the subsequent data set comprises a plurality of subsequent data points representing optical property values corresponding to specified, spatially resolved subsequent locations in the area of interest, the control data set comprises a plurality of control data points representing optical property values corresponding to specified, spatially resolved control locations in the area of interest, wherein the subsequent locations and the control locations are at the same spatial locations in the area of interest.

12. A method according to claim 1, wherein the subsequent data set and the control data set each include a plurality of data points that are spatially resolved with respect to the area of interest, and the comparison data set compares control and subsequent data points having the same spatial location in the area of interest.

21. A method according to any of claims 1, 13, 11 or 19, wherein the optical detector is a video camera.

22. A method according to any of claims 1, 13, 11 or 19, additionally comprising amplifying portions of the control data set to enhance the contrast of the comparison data set.

24. A method according to claim 11, wherein each of the control data points and the subsequent data points is detected using a CCD apparatus.

25. A method according to claim 11, additionally comprising acquiring a plurality of control data sets and a plurality of subsequent data sets, averaging the plurality of each of the control data sets to produce an averaged control data set, and averaging the plurality of each of the subsequent data sets, and comparing the averaged subsequent data set with the averaged control data set.

26. A method according to claim 11 or 19, wherein the area of interest is located underneath at least one of intact skin and bone, and the illuminating and detecting takes place through the at least one of intact skin and bone.

27. A method according to claim 11 or 19, wherein the comparison data set is an image and processing provides an enhanced contrast color image.

28. A method according to claim 11, wherein comparing the subsequent data set with a control data set to distinguish tumor from non-tumor tissue in each of the spatially resolved locations in the area of interest distinguishes between positive-going and negative-going changes.

29. A method according to any of claims 1, 13 or 19, comprising illuminating the area of interest with uniform intensity emr.

30. A method according to any of claims 1, 13 or 19, comprising illuminating the area of interest with non-continuous illumination.

31. A method according to any of claims 1, 13 or 19, comprising illuminating the area of interest with an illumination source using at least one of the following:

amplitude modulated;

frequency modulated; and

phase modulated techniques.

32. A method according to any of claims 1, 13, 11 or 19, comprising producing the comparison data set in real-time.

33. A method according to claim 11, wherein one or more spatially resolved locations in the area of interest is detected using at least one of the following detectors:

at least one photodiode;

at least one photomultiplier tube;

at least one camera;

at least one video camera; and

at least one CCD camera.

34. A method according to claim 11, wherein one or more spatially resolved locations in the area of interest is is illuminated using at least one of the following sources:

a tungsten-halogen lamp;

a laser;

a laser diode; and

a light-emitting diode.

35. A method according to any of claims 1, 13, or 19, wherein at least one blood characteristic is monitored simultaneously with differences in the dynamics of dye perfusion in tumor and non-tumor tissue in the area of interest.

36. A method according to any of claims 1, 13, or 19, wherein the area of interest is illuminated using at least one optical fiber operably connected to an emr source.

37. A method according to any of claims 1, 13, or 19, wherein the area of interest is detected using at least one optical fiber operably connected to an optical detector.

38. A method according to any of claims 1, 13, 11 or 38 wherein the area of interest is breast tissue.

39. A method according to any of claims 1, 13, 11 or 19, wherein the dye is indocyanine green.

40. A method according to any of claims 1, 13 or 19, wherein the dye is conjugated to a targeting molecule.

13. 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;

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

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

(d) comparing the subsequent data set with a control data set representing the one or more optical properties of the area of interest to produce a comparison data set; and

(e) differentiating grades of tumors in the area of interest based on differences in the one or more optical properties evidenced in the comparison data set, the differences in the one or more optical properties representing different dynamics of dye perfusion in different grades of tumor tissue.

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

15. A method according to claim 13, wherein the area of interest is located underneath at least one of intact skin and bone and the emr is in the infrared region.

16. A method according to claim 13, step (c), wherein detecting is carried out with a CCD apparatus.

17. A method according to claim 13, additionally comprising compensating for movement in the area of interest by aligning markers indicating corresponding spatial locations in the control and subsequent data sets to produce the comparison data set.

18. A method according to claim 13, 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.

19. A method for detecting the presence of tumor tissue in an area of interest suspected to contain tumor tissue comprising:

(a) illuminating the area of interest with at least two different wavelengths of electromagnetic radiation (emr);

(b) obtaining a sequence of control data sets corresponding to the area of interest for each wavelength of emr;

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

(d) obtaining a sequence of subsequent data sets corresponding to the area of interest for each wavelength of emr following administration of the dye; and

(e) obtaining a series of comparison data sets for each wavelength of emr by subtracting one of the control data set and the subsequent data set from the other of the control data set and the subsequent data set.

20. A method according to claim 19, additionally comprising obtaining an enhanced comparison data set by ratioing a first comparison data set to a second comparison data set.

23. A method according to claim 19, additionally comprising displaying the comparison data set in a visual image format.