Tumor demarcation using optical spectroscopy

• US 6,377,841 B1
• Filed: 04/07/2000
• Issued: 04/23/2002
• Est. Priority Date: 03/31/2000
• Status: Expired due to Fees

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Mahadevan-Jansen, Anita, Jansen, E. Duco, Lin, Wei-Chiang, Toms, Steven A.
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): SHAW, SHAWNA JEANNINE
• Application Number:
  US09/545,425
• Time in Patent Office: 746 Days
• Field of Search: 600/407, 600/473-478, 356/302, 356/303, 356/341, 356/342
• US Class Current: 600/477
• 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 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

Optical spectroscopy for brain tumor demarcation was investigated in this study. Fluorescence and diffuse reflectance spectra were measured from normal and tumorous human brain tissues in vitro. A fluorescence peak was consistently observed around 460 nm (±10 nm) emission from both normal and tumorous brain tissues using 337 nm excitation. Intensity of this fluorescence peak (F₄₆₀) from normal brain tissues was greater than that from primary brain tumorous tissues. In addition, diffuse reflectance (Rd) between 650 nm and 800 nm from white matter was significantly stronger than that from primary and secondary brain tumors. A good separation between gray matter and brain tumors was found using the ratio of F₄₆₀ and Rd at 400 nm-600 nm. Two empirical discrimination algorithms based on F (400 nm-600 nm), Rd (600 nm-800 nm), and F (400 nm-600 nm)/Rd (400 nm-600 nm) were developed. These algorithms yielded an average sensitivity and specificity of 96% and 93%, respectively.

Claims

1. A system for brain tumor margin detection comprising:

a source of white light;

a source of laser light at a wavelength of about 330-360 nm;

a fiber optic probe coupled with the source of white light and the source of laser light so as to deliver the white light and the laser light to a working end of the probe;

a spectroscope coupled with the fiber optic probe so as to receive autofluorescent and diffuse reflectance light returned from tissue contacted by the working end of the probe and provide a frequency spectrum of the returned light;

a system controller including a processor coupled with the spectroscope and programmed to analyze a ratio of fluorescent light and diffuse reflectance light delivered to the spectrometer by the fiber optic probe to distinguish between light returned to the spectroscope from tumorous and from non-tumorous tissues.

2. The system of claim 1 wherein the processor identifies tumorous brain tissue contacted by the working end of the probe based in part upon intensity of fluorescence light at about 400-600 nm delivered to the spectrometer by the fiber optic probe.

3. The system of claim 1 wherein the processor identifies tumorous brain tissue contacted by the working end of the probe based at least in part upon intensity of diffuse reflectance light at between about 400 nm and 800 nm returned to the spectrometer by the probe.

4. The system of claim 1 wherein the processor identifies tumorous brain tissue contacted by the working end of the probe based at least in part upon the ratio of the intensity of fluorescence and diffuse reflectance light between about 400 nm and 600 nm returned to the spectrometer by the probe.

5. The system of claim 1 in combination with a free electron laser configured to be guided by the system processor.

6. The system of claim 1 wherein the system controller generates a signal representing a ratio of intensity of autofluorescent light at a first frequency obtained from an area of brain tissue illuminated in vivo by the laser light source and intensity of diffuse reflectance light at the first frequency obtained from the same area of brain tissue illuminated in vivo by the white light source.

7. The system of claim 6 wherein the first frequency is between 400 nm and 600 nm.

8. The system of claim 6 wherein the system controller generates another signal representing intensity of diffuse reflectance light at a second frequency above the first frequency and obtained from the same area brain tissue in response to the same in vivo illumination of the area of the brain tissue by the white light source.

9. The system of claim 8 wherein the second predetermined frequency is between 600 nm and 800 nm.

10. A system for brain tumor margin detection comprising:

a white light source emitting broad band light from at least 400 nm to at least 850 nm;

a laser light source emitting coherent light at a wavelength between 330 nm and 360 nm;

a fiber optic probe coupled with the white light source and the laser light source so as to deliver in vivo the white light and the laser light to an area of brain tissue proximal a working end of the probe;

a spectroscope coupled with the fiber optic probe so as to receive from the working end of the probe, autofluorescent light emitted from the area in response to illumination by the coherent light and diffuse reflectance light reflected from the same area in response to illumination by the white light; and

a system controller operatively coupled with the spectroscope and configured to generate a plurality of signals, at least one signal representing a ratio of intensity of the autofluorescent light at a first wavelength obtained from the area of brain tissue in response to illumination of the area by the coherent light and intensity of the diffuse reflectance light at the same first wavelength also obtained from the same area of the brain tissue in response to illumination of the area by the white light.

11. A method of using the system of claim 10 comprising the steps of:

illuminating in vivo the area of brain tissue separately with the laser light source and the white light source;

separately gathering with the fiber optic probe, the autofluorescent light emitted in the brain tissue area in response to the laser light source and diffuse reflectance light passed through the brain tissue area illuminated by the white light source;

generating the signal representing the ratio of intensity of the autofluorescent light at the first wavelength and intensity of the diffuse reflectance light at the same first wavelength; and

comparing magnitude of the ratio signal to a predetermined magnitude value to determine in vivo tumor presence in the illuminated brain tissue area.

12. The method of claim 11 further comprising the step of calibrating the autofluorescent light against an independent standard before the using step.

13. The method of claim 11 further comprising the step of calibrating the diffuse reflectance light against an independent standard before the using step.

14. A system for brain tumor margin detection comprising:

means for illuminating in vivo brain tissue with electromagnetic radiation at optical wavelengths;

means for collecting electromagnetic radiation at optical wavelengths returned from the illuminated in vivo brain tissue;

means for correcting intensities of the collected electromagnetic radiation at at least one wavelength for non-uniform spectral response of the system; and

means responsive to the corrected intensities for generating diagnostic signals indicative of histopathological characteristics of the illuminated brain tissue.

15. The system of claim 14 wherein at least one of the generated diagnostic signals represents a ratio of intensity of autofluorescence emitted in vivo from an illuminated area of the brain tissue and intensity of diffuse reflectance from the same area of the brain tissue illuminated with white light.

16. The system of claim 15 wherein the at least one generated diagnostic signal represents the ratio of autofluorescence intensity at a first wavelength and diffuse reflectance intensity at the same first wavelength.

17. The system of claim 16 wherein the first wavelength is in the range of 400 nm to 600 nm.

18. The system of claim 17 wherein the first wavelength is about 460 nm.

19. A method of using the system of claim 14 comprising the steps of:

illuminating in vivo an area of brain tissue with the electromagnetic radiation;

collecting electromagnetic radiation returned from the illuminated in vivo area of brain tissue;

correcting intensities of at least a plurality of wavelengths of the electromagnetic radiation collected from the illuminated area of the brain tissue using independent intensity standards; and

using the corrected wavelength intensities to identify brain tumor presence in the illuminated area of in vivo brain tissue.

20. The method of claim 19 wherein the using step comprises the step of generating a ratio of corrected intensity of autofluorescent light emitted in vivo by the illuminated area of the brain and corrected intensity of diffuse reflectance of white light in the illuminated area of the brain.