Method and apparatus for examining a tissue using the spectral wing emission therefrom induced by visible to infrared photoexcitation

• US 6,665,556 B1
• Filed: 01/28/2000
• Issued: 12/16/2003
• Est. Priority Date: 01/29/1999
• Status: Expired due to Fees

• Current Assignee: City College of New York
• Original Assignee: City College of New York
• Inventors: Zhang, Gang, Demos, Stavros G., Alfano, Robert R.
• Primary Examiner(s): Manuel, George
• Assistant Examiner(s): QADERI, RUNA S
• Application Number:
  US09/493,939
• Time in Patent Office: 1,418 Days
• Field of Search: 600/425, 600/473, 600/475, 600/476, 600/477, 436/63, 436/64
• US Class Current: 600/473
• CPC Class Codes: A61B 1/043 for fluorescence imaging
• CPC Class Codes: A61B 1/063 for monochromatic or narrow-band illumination
• CPC Class Codes: A61B 1/0638 providing two or more wavelengths
• 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

Abstract

Method and an apparatus for examining a tissue using the spectral wing emission therefrom induced by visible to infrared photoexcitation. In one aspect, the method is used to characterize the condition of a tissue sample and comprises the steps of (a) photoexciting the tissue sample with substantially monochromatic light having a wavelength of at least 600 nm; and (b) using the resultant far red and near infrared spectral wing emission (SW) emitted from the tissue sample to characterize the condition of the tissue sample. In one embodiment, the substantially monochromatic photoexciting light is a continuous beam of light, and the resultant steady-state far red and near infrared SW emission from the tissue sample is used to characterize the condition of the tissue sample. In another embodiment, the substantially monochromatic photoexciting light is a light pulse, and the resultant time-resolved far red and near infrared SW emission emitted from the tissue sample is used to characterize the condition of the tissue sample. In still another embodiment, the substantially monochromatic photoexciting light is a polarized light pulse, and the parallel and perpendicular components of the resultant polarized time-resolved SW emission emitted from the tissue sample are used to characterize the condition of the tissue sample.

Claims

1. A method for characterizing the condition of a native tissue sample as being one of normal, benign, precancerous and cancerous, said method comprising the steps of:

(a) photoexciting the native tissue sample with substantially monochromatic light having a wavelength of at least 600 nm, whereby a far red and near infrared spectral wing emission is emitted from the native tissue sample; and

(b) using at least the far red and near infrared spectral wing emission emitted from the native tissue sample to characterize the condition of the native tissue sample as being one of normal, benign, precancerous and cancerous.

2. The method as claimed in claim 1 wherein the substantially monochromatic photoexciting light is a continuous beam of light, wherein said native far red and near infrared spectral wing emission from the tissue sample includes native steady-state far red and near infrared spectral wing emission and wherein said using step comprising using said native steady-state far red and near infrared spectral wing emission emitted from the tissue sample to characterize the condition of the tissue sample.

3. The method as claimed in claim 2 wherein the substantially monochromatic photoexciting light has a wavelength in the range of about 600 to 980 nm and wherein said native steady-state far red and near infrared spectral wing emission has a wavelength of at least 20 nm greater than said substantially monochromatic photoexciting light.

4. The method as claimed in claim 3 wherein the substantially monochromatic photoexciting light has a wavelength of about 632 nm and wherein said native steady-state far red and near infrared spectral wing emission wavelengths are 650 nm to 950 nm.

5. The method as claimed in claim 3 wherein the substantially monochromatic photoexciting light has a wavelength of about 800 nm and wherein said native steady-state far red and near infrared spectral wing emission wavelengths are 840 to 950 nm.

6. The method as claimed in claim 2 wherein said using step comprises obtaining a spectral profile of the spectral wing emission emitted from the tissue sample and comparing said spectral profile to standards obtained from tissues whose conditions are known over wavelengths greater than 750 nm.

7. The method as claimed in claim 6 wherein said using step comprises determining a normalized integrated intensity of the spectral profile and comparing said normalized integrated intensity to appropriate standards.

8. The method as claimed in claim 6 wherein said using step comprises determining a ratio or difference of intensities at two wavelengths along said spectral profile and comparing said ratio or difference to appropriate standards.

9. The method as claimed in claim 2 wherein said using step comprises detecting the native steady-state far red and near infrared spectral wing at two wavelengths, determining a ratio or difference of intensities at said two wavelengths and comparing said ratio or difference to appropriate standards.

10. The method as claimed in claim 1 wherein the substantially monochromatic photoexciting light is a light pulse and wherein said using step comprises using the resultant time-resolved native fluorescence emitted from the native tissue sample to characterize the condition of the native tissue sample.

11. The method as claimed in claim 10 wherein the substantially monochromatic photoexciting light has a wavelength in the range of about 600 to 980 nm and wherein said native time-resolved fluorescence has a wavelenghth greater than 20 nm than said substantially monochromatic photoexciting light.

12. The method as claimed in claim 11 wherein the substantially monochromatic photoexciting light has a wavelength of about 632 nm and wherein said native time-resolved fluorescence has a wavelength in the range of 650 to 950 nm.

13. The method as claimed in claim 10 wherein the substantially monochromatic photoexciting light is produced by a diode laser.

14. The method as claimed in claim 10 wherein said using step comprises obtaining a profile of the time-resolved spectral wing emitted from the native tissue sample and comparing said profile to standards obtained from tissues whose conditions are known.

15. The method as claimed in claim 14 wherein said comparing step comprises fitting the profile to the formula I(t)=A₁e⁽⁻

t/τ

1)+A₂e<sup>(−

t/τ

2)</sup> and comparing the resultant values for at least one of A₁/A₂ and τ

₁ with appropriate standards.

16. The method as claimed in claim 1 wherein the substantially monochromatic photoexciting light is a polarized light pulse and wherein said using step comprises using at least one of the parallel and perpendicular components of the resultant polarized time-resolved spectral wing emitted from the native tissue sample to characterize the condition of the native tissue sample.

17. The method as claimed in claim 16 wherein the substantially monochromatic photoexciting light has a wavelength in the range of about 600 to 980 nm and wherein said far red and near infrared spectral wing emission has a wavelength greater than 20 nm than the substantially monochromatic photoexciting light.

18. The method as claimed in claim 17 wherein the substantially monochromatic photoexciting light has a wavelength of about 632 nm and wherein said far red and near infrared spectral wing emission has a wavelength from 650 nm to 950 nm.

19. The method as claimed in claim 16 wherein said using step comprises obtaining a profile of at least one of the parallel and perpendicular components and comparing said profile(s) to standards obtained from tissues whose conditions are known.

20. The method as claimed in claim 1 wherein the tissue sample is a human tissue sample.

21. The method as claimed in claim 20 wherein the tissue sample is selected from the group consisting of the colon, mucosa, prostate, bladder, GI tract, cervix, uterus, GYN tract, brain, lung, bronchus and skin.

22. The method as claimed in claim 20 wherein the method is used to diagnose the breast cancer from normal human breast tissue from SW emission wavelength profiles.

23. A method for diagnosing Alzheimer'"'"'s disease in human brain tissues said method comprising the steps of:

(a) photoexciting the native human tissue sample with substantially monochromatic light having a wavelength of at least 600 nm, whereby a far red and near infrared spectral wing emission is emitted from the native human tissue sample; and

(b) using at least the far red and near infrared spectral wing emission emitted from the native human tissue sample to diagnose Alzheimer'"'"'s disease in the native human tissue sample.

24. A method for diagnosing diabetes disease in native human tissues said method comprising the steps of:

(a) photoexciting the native human tissue sample with substantially monochromatic light having a wavelength of at least 600 nm, whereby a far red and near infrared spectral wing emission is emitted from the native human tissue sample; and

(b) using at least the far red and near infrared spectral wing emission emitted from the native human tissue sample to diagnose diabetes disease in the native human tissue sample.

25. A method for imaging a native tissue sample, said method comprising the steps of.

(a) photoexciting the native tissue sample with substantially monochromatic light having a wavelength of at least 600 nm, whereby a far red and near infrared spectral wing emission is emitted from the native tissue sample;

and

(b) using at least the far red and near infrared spectral wing emission emitted from the native tissue sample to form an image of the native tissue sample.

26. The method as claimed in claim 25 wherein the substantially monochromatic photoexciting light has a wavelength in the range of about 600 to 980 nm and wherein said native fluorescence has a wavelength of at least 20 nm more than said substantially monochromatic photoexciting light.

27. The method as claimed in claim 25 further comprising the step of using the image of the native tissue sample to characterize the condition of the imaged native tissue sample.

28. An apparatus for imaging a native tissue sample, said apparatus comprising:

(a) a light source for photoexciting the native tissue sample with substantially monochromatic light having a wavelength of at least 730 nm;

(b) a light detector;

(c) collection optics for imaging the light emitted from the native tissue sample onto the light detector;

(d) filter means positioned between the native tissue sample and the light detector for selectively transmitting, from the light emitted from the native tissue sample, light having a wavelength greater than said substantially monochromatic light at least 20 nm greater than excitation wavelength; and

(c) a display coupled to said light detector for displaying an image of the native tissue sample based on the light detected by said light detector.

29. The apparatus as claimed in claim 28 wherein said light source emits substantially monochromatic light having a wavelength in the range of about 600 to 980 nm and emissions of spectral wing at wavelengths greater than 20 nm from excitation wavelength.

30. The apparatus as claimed in claim 28 wherein said light source is selected from the group consisting of a laser and the combination of a lamp and a narrow band filter.

31. The apparatus as claimed in claim 30 wherein said light source is a laser.

32. The apparatus as claimed in claim 28 wherein said light detector is selected from the group consisting of a CCD camera, a photomultiplier and a photodiode.

33. The apparatus as claimed in claim 32 wherein said light detector is a CCD camera.

34. The apparatus as claimed in claim 28 wherein said filter means comprises a filter selected from the group consisting of a bandpass filter, a long wavelength pass filter and a narrow band filter.

35. The apparatus as claimed in claim 28 wherein said filter means comprises a filter wheel and a plurality of filters, each of said filters being selective for a different emission wavelength.

36. The apparatus as claimed in claim 28 further comprising an endoscope for use in transmitting light from said light source to the tissue sample and for use in transmitting light from the tissue sample to said light detector.

37. The apparatus as claimed in claim 28 further comprising means for characterizing the condition of the native tissue sample.