Optimal windows for obtaining optical data for characterization of tissue samples

• US 6,933,154 B2
• Filed: 11/15/2002
• Issued: 08/23/2005
• Est. Priority Date: 07/09/2002
• Status: Expired due to Fees

• Current Assignee: Luma Imaging Corp. (SpectraScience, Inc.)
• Original Assignee: MediSpectra, Inc. (SpectraScience, Inc.)
• Inventors: Flewelling, Ross, Kaufman, Howard, Schomacker, Kevin T., Zelenchuk, Alex
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Siefke, Sam P.
• Application Number:
  US10/295,794
• Publication Number:
  US 20040023406A1
• Time in Patent Office: 1,012 Days
• Field of Search: 424/9.8, 424/9.1, 514/557, 600/407, 600/408, 600/310, 436/172
• US Class Current: 436/164
• 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 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: A61B 5/7267 involving training the classification device
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

The invention provides methods for determining a characteristic of a tissue sample, such as a state of health, using spectral data and/or images obtained within an optimal period of time following the application of a chemical agent to the tissue sample. The invention provides methods of determining such optimal windows of time. Similarly, the invention provides methods of determining other criteria for triggering the acquisition of an optical signal for classifying the state of health of a region of a tissue sample.

Claims

1. A method of identifying a characteristic of a region of a tissue sample, the method comprising the steps of:

(a) applying a contrast agent comprising acetic acid to a region of a tissue sample;

(b) obtaining at least one optical signal from the region within a window of time, wherein the window of time begins at about 30 seconds following application of the contrast agent and ends at about 130 seconds following application of the contrast agent, and wherein the at least one optical signal comprises at least one of;

(i) a fluorescence signal; and

(ii) a reflectance signal; and

(c) identifying a characteristic of the region based at least in part on the at least one optical signal.

2. The method of claim 1, wherein the at least one optical signal comprise a reflectance intensity.

3. The method of claim 1, wherein the at least one optical signal comprise a fluorescence intensity.

4. The method of claim 1, wherein the at least one optical signal comprises at least one of a group consisting of fluorescence, reflectance, Raman, infrared, and video signals.

5. The method of claim 1, wherein the characteristic is a state of health.

6. The method of claim 5, wherein the state of health comprises at least one of the group consisting of normal squamous tissue, normal columnar tissue, metaplasia, immature metaplasia, mature metaplasia, CIN 1, CIN 2, CIN 3, CIS, and cancer.

7. The method of claim 1, wherein the identifying of step (c) comprise determining whether the region of the tissue sample is CIN 2+ tissue.

8. The method of claim 1, wherein the tissue sample comprises cervical tissue.

9. The method of claim 1, wherein the tissue sample comprises at least one of a group consisting of colorectal tissue, gastroesophageal tissue, urinary bladder tissue, lung tissue, and skin tissue.

10. The method of claim 1, wherein the tissue sample comprises epithelial cells.

11. The method of claim 1, wherein the at least one optical signal comprises a fluorescence signal and a reflectance signal.

12. The method of claim 1, wherein the at least one optical signal comprise two reflectance signals.

13. The method of claim 1, wherein the at least one optical signal comprise a fluorescence signal and two reflectance signals.

14. The method of claim 1, wherein the at least one optical signal comprise a fluorescence signal, a reflectance signal, and a video signal.

15. The method of claim 1, wherein step (b) comprises obtaining the at least one optical signal from the region within a period-of time that begins at about 60 seconds following application of the contrast agent and ends at about 80 seconds following application of the contrast agent.

16. The method of claim 1, wherein step (b) comprises obtaining the at least one optical signal from the region within a period of time that begins at about 70 seconds following application of the contrast agent and ends at about 130 seconds following application of the contrast agent.

17. The method of claim 1, wherein step (c) comprises identifying the characteristic of the region with an accuracy of at least about 70%.

18. The method of claim 1, wherein step (b) comprises obtaining a reflectance intensity from the region at each of a plurality of wavelengths within the window of time.

19. The method of claim 18, wherein step (b) further comprises obtaining a fluorescence intensity from the region at each of a plurality of wavelengths within the window of time.

20. The method of claim 19, wherein step (b) further comprises obtaining a video signal from the region within the window of time.

21. The method of claim 1, wherein step (a) comprises applying a contrast agent to a plurality of regions of the tissue sample;

step (b) comprises obtaining at least one optical signal from each of the plurality of regions within the window of time; and

step c) comprises identifying a characteristic of each of the plurality of regions.

22. The method of claim 1, wherein step (c) comprises identifying the characteristic of the region based substantially on the at least one optical signal.

23. The method of claim 1, wherein the contrast agent comprises an acetic acid solution at a concentration between about 3 volume percent and about 6 volume percent.

24. The method of claim 23, wherein the contrast agent comprises an acetic acid solution at a concentration of about 5 volume percent.