Spectral diagnosis of diseased tissue

• US 5,421,337 A
• Filed: 03/29/1994
• Issued: 06/06/1995
• Est. Priority Date: 04/14/1989
• Status: Expired due to Term

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Richards-Kortum, Rebecca, Feld, Michael S., Tong, Lucene
• Primary Examiner(s): Sykes, Angela D.
• Application Number:
  US08/219,240
• Time in Patent Office: 434 Days
• Field of Search: 128/6, 128/633-634, 128/664-665, 436/171-172
• US Class Current: 600/477
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/42 Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems A61B1/00, A61B5/4857, A61B5/486, A61B5/4866, A61B5/4869 take precedence

Abstract

The present invention relates to a method and apparatus for diagnosing the condition of gastrointestinal tissue. The method and apparatus excite fluorophores within a portion of gastrointestinal tissue with a laser to cause the fluorophores to emit fluorescent radiation. The presence of abnormal tissue is then determined by detecting the radiation emitted by the excited fluorophores and comparing the emitted radiation to a reference emission for fluorophores within normal tissue at predetermined wavelengths.

Claims

1. A method of diagnosing gastrointestinal tissue to determine the presence of abnormal tissue comprising:

exciting fluorophores within a portion of gastrointestinal tissue with light at a predetermined wavelength which causes the fluorophores within the tissue to emit autofluorescent radiation of a plurality of wavelengths without the presence of a fluorescence enhancing agent;

detecting the autofluorescent radiation emitted by the fluorophores within the tissue in response to excitation from the light to provide an emission spectrum;

forming an attenuation spectrum and comDarinq the attenuation spectrum with the emission spectrum to identify fluorophores within the tissue; and

analyzing the emission spectrum to determine the presence of abnormal tissue within the portion of tissue containing the excited fluorophores by comparing the emission spectrum to a reference emission for normal tissue at a plurality of predetermined wavelengths.

2. The method of diagnosing gastrointestinal tissue of claim 1 wherein the analyzing step further comprises determining a ratio of an intensity of the emission fluorescence at one of the emission wavelengths with an intensity of the emission fluorescence at another of the emission wavelengths and comparing the ratio with a threshold ratio for normal tissue.

3. The method of diagnosing gastrointestinal tissue of claim 2 further comprising determining the ratio of wavelengths having a maximum separation between normal and abnormal tissue.

4. The method of diagnosing gastrointestinal tissue of claim 2 wherein the excitation wavelength is 290 nm and the emission wavelength ratio is selected from the group of wavelengths consisting of about 335 nm/365 nm, 335 nm/440 nm, 440 nm/390 nm, 415 nm/425 nm, or 440 nm/457 nm.

5. The method of diagnosing gastrointestinal tissue of claim 2 wherein the excitation wavelength is 350 nm and the emission wavelength ratio is selected from the group of wavelengths consisting of 387 nm/365 nm, 387 nm/427 nm, 415 nm/425 nm, 440 nm/457 nm, 495 nm/440 nm, or 475 nm/440 nm.

6. The method of diagnosing gastrointestinal tissue of claim 1 to determine the presence of abnormal tissue further comprising:

exciting fluorophores within a portion of the gastrointestinal tissue with light having a wavelength in a range between 200 and 400 nanometers such that the fluorophores within the tissue fluoresces; and

detecting radiation emitted by the fluorophores within the tissue having a wavelength in a range between 300 and 600 nanometers.

7. The method of diagnosing gastrointestinal tissue of claim 6 further comprising identifying a plurality of selected wavelengths in the emission range that distinguish between normal and abnormal tissue and comparing the emitted radiation at the selected wavelengths with a reference emission for normal tissue at the selected wavelengths.

8. The method of diagnosing gastrointestinal tissues of claim 6 wherein the excitation wavelength is within the range between 330 and 370 nanometers.

9. The method of diagnosing gastrointestinal tissues of claim 6 wherein the emission wavelength is about 440 nanometers.

10. The method of diagnosing gastrointestinal tissue of claim 6 wherein the emission wavelength is about 470 nanometers.

11. The method of diagnosing gastrointestinal tissue of claim 6 wherein the emission wavelength is about 385 nanometers.

12. The method of diagnosing gastrointestinal tissue of claim 6 wherein the emission wavelength is about 560 nanometers.

13. The method of diagnosing gastrointestinal tissue of claim 1 wherein the exciting step further comprises:

inserting a fiber optic probe having an optical fiber into a body lumen;

contacting the tissue to be diagnosed with a distal surface of the fiber optic probe such that radiation transmitted along the fiber will be directed onto the tissue from the distal surface;

coupling a source of laser radiation to a proximal end of the fiber optic probe such that laser radiation is transmitted along the optical fiber and onto the tissue; and

wherein the detecting step further comprises

transmitting autofluorescent radiation emitted by the fluorophores within the tissue from the distal end of the fiber optic probe to the proximal end.

14. The method of diagnosing gastrointestinal tissue of claim 13 wherein the analyzing step further comprises comparing a characteristic of the detected radiation with a reference signal to determine the presence of abnormal tissue within the irradiated portion.

15. The method of diagnosing gastrointestinal tissue of claim 1 wherein the fluorophores are selected from the group consisting of tryptophan, NADH, NADPH, 4-pyridoxic acid, pyridoxal 5'"'"'-phosphate, pyridoxic acid lactone and porphyrins.

16. The method of diagnosing gastrointestinal tissue of claim 15 wherein the fluorophores are excited with light of wavelengths selected from the group consisting of about 275 nm, 300 nm, 305 nm, 350 nm, 360 nm, 400 nm and 410 nm.

17. The method of diagnosing gastrointestinal tissue of claim 16 wherein the radiation emitted by the fluorophores is of wavelengths selected from the group consisting of about 350 nm, 375 nm, 430 nm, 435 nm, 460 nm, 520 nm, 610 nm and 675 nm.

18. A method of determining a function for diagnosing gastrointestinal tissue comprising:

irradiating fluorophores within a portion of gastrointestinal tissue with light of selected wavelength from a laser;

inducing autofluorescence of the fluorophores within the portion of tissue;

detecting the autofluorescent radiation emitted by the fluorophores within the tissue;

generating an emission spectrum from the detected radiation;

determining a difference spectrum by calculating the difference between the emission spectrum and a reference spectrum;

selecting a first wavelength from the difference spectrum where the irradiated portion has a relative maximum fluorescence in relation to surroundinq wavelengths;

selecting a second wavelength from the difference spectrum where the reference spectrum has a relative maximum fluorescence in relation to surroundinq wavelengths; and

determining a diagnostic function from the first and second wavelengths to differentiate abnormal from normal tissue.

19. The method of claim 18 further comprising:

determining a first standard deviation spectrum for the reference spectrum and determining a second standard deviation spectrum from the emission spectrum;

determining a discriminant spectrum from the difference spectrum and the first and second deviation spectrum;

selecting wavelengths within the discriminant spectrum to form a diagnostic function to differentiate abnormal from normal tissue.

20. The method of diagnosing gastrointestinal tissue of claim 18 wherein the fluorophores are selected from the group consisting of tryptophan, NADH, NADPH, 4-pyridoxic acid, pyridoxal 5'"'"'-phosphate, pyridoxic acid lactone and porphyrins.

21. The method of diagnosing gastrointestinal tissue of claim 20 wherein the fluorophores are irradiated with light of wavelengths selected from the group consisting of about 275 nm, 300 nm, 305 nm, 350 nm, 360 nm, 400 nm and 410 nm.

22. The method of diagnosing gastrointestinal tissue of claim 21 wherein the radiation emitted by the fluorophores is of wavelengths selected from the group consisting of about 350 nm, 375 nm, 430 nm, 435 nm, 460 nm, 520 nm, 610 nm and 675 nm.

23. A diagnostic probe to determine the presence of abnormal tissue comprising:

a source of laser radiation having a wavelength of between about 370 nm and about 450 nm;

a fiber optic probe having a plurality of optical fibers such that a first fiber is coupled to the radiation source at a proximal end and directs the radiation onto an irradiated area of tissue containing fluorophores adjacent a distal end of the first fiber to induce autofluorescence of the fluorophores, the plurality of fibers including a collection fiber that is positioned relative to the plurality of fibers to receive autofluorescent radiation from only the fluorophores within the irradiated area of tissue;

an analyzer coupled to a proximal end of the collection fiber that receives and analyzes the fluorescent radiation from the fluorophores within the irradiated area at wavelenqths lonqer than 400 nm.

24. The diagnostic probe of claim 23 wherein the analyzer generates a signal correllated with the intensity of the fluorescent radiation at 460 nm,

25. The diagnostic probe of claim 23 further comprising a plurality of collection fibers.

26. The diagnostic probe of claim 23 further comprising a second laser source to deliver an energy pulse to the tissue to treat the tissue.