Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies

• US 5,697,373 A
• Filed: 03/14/1995
• Issued: 12/16/1997
• Est. Priority Date: 03/14/1995
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Ramanujam, Nirmala, Richards-Kortum, Rebecca, Mitchell, Michele Follen, Mahadevan, Anita
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): SHAW, SHAWNA JEANNINE
• Application Number:
  US08/403,446
• Time in Patent Office: 1,008 Days
• Field of Search: 128/664, 128/665, 250/461.2, 356/301, 356/317, 356/318, 356/417, 356/73
• US Class Current: 600/475
• 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 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/4331 of the cervix A61B5/435 takes 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: G01N 2021/656 Raman microprobe
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.

Claims

1. A method of detecting and quantifying tissue abnormality in a tissue sample, comprising:

illuminating said tissue sample with a first electromagnetic radiation wavelength selected to cause said tissue sample to produce a fluorescence intensity spectrum indicative of tissue abnormality;

detecting a first fluorescence intensity spectrum emitted from said tissue sample as a result of illumination with said first wavelength;

illuminating said tissue sample with a second electromagnetic radiation wavelength selected to cause said tissue sample to produce a fluorescence intensity spectrum indicative of a degree of tissue abnormality;

detecting a second fluorescence intensity spectrum emitted from said tissue sample as a result of illumination with said second wavelength;

calculating from said first fluorescence intensity spectrum, a probability that said tissue sample is normal or abnormal; and

calculating from said second fluorescence intensity spectrum a degree of abnormality of said tissue sample.

2. The method of claim 1, each of said calculating steps comprising:

conducting principal component analysis of said first and second spectra, relative to a plurality of preprocessed spectra obtained from tissue samples of known diagnosis.

3. The method of claim 1, each of said calculating steps comprising:

normalizing said first and second spectra, relative to a maximum intensity within said spectra.

4. The method of claim 3, each of said calculating steps further comprising:

mean-scaling said first and second spectra as a function of a mean intensity of said first and second spectra.