Method for determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue using Raman spectroscopy

• US 5,261,410 A
• Filed: 02/07/1991
• Issued: 11/16/1993
• Est. Priority Date: 02/07/1991
• Status: Expired due to Fees

• Current Assignee: The Research Foundation of State University of New York
• Original Assignee: Cheng H. Liu, Robert R. Alfano, Wenling S. Glassman
• Inventors: Glassman, Wenling S., Alfano, Robert R., Liu, Cheng H.
• Primary Examiner(s): Smith, Ruth S.
• Application Number:
  US07/651,449
• Time in Patent Office: 1,013 Days
• Field of Search: 128/664, 128/665, 128/395, 128/397, 128/398, 356/301, 250/339-341
• US Class Current: 600/475
• 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 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/0091 for mammography
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence
• CPC Class Codes: G01N 2021/656 Raman microprobe
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

A method for determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue. The present method is based on the discovery that, when irradiated with a beam of infrared, monochromatic light, malignant tumor tissue, benign tumor tissue, and normal or benign tissue produce distinguishable Raman spectra. For human breast tissue, some salient differences in the respective Raman spectra are the presence of four Raman bands at a Raman shift of about 1078, 1300, 1445, and 1651 cm^-1 for normal or benign tissue, the presence of three Raman bands at a Raman shift of about 1240, 1445, and 1659 cm^-1 for benign tumor tissue, and the presence of two Raman bands at a Raman shift of about 1445 and 1651 cm^-1 for malignant tumor tissue. In addition, it was discovered that for human breast tissue the ratio of intensities of the Raman bands at a Raman shift of about 1445 and 1659 cm^-1 is about 1.25 for normal or benign tissue, about 0.93 for benign tumor tissue, and about 0.87 for malignant tumor tissue.

Claims

1. A method for determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue comprising the steps of:

a) irradiating the tissue with a beam of infrared monochromatic light;

b) obtaining the infrared Raman spectrum for the tissue in the Raman spectral region from 700 to 1900 cm^-1 ; and

c) comparing said infrared Raman spectrum so obtained for the tissue with infrared Raman spectra correspondingly obtained from known samples of malignant tumor tissue, benign tumor tissue, and normal or benign tissue for the same type of tissue being tested.

2. The method of claim 1 wherein the tissue being tested is human tissue.

3. The method of claim 2 wherein the human tissue is derived from a part of the body selected from the group consisting of the vagina, the cervix, the uterus, the ovaries, the rectum, the colon, the brain, the bladder, the skin, the breast, the stomach, the lung and the mouth.

4. The method of claim 3 wherein the human tissue is derived from the breast.

5. A method of determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a benign or normal tissue, comprising the steps of:

a) irradiating the tissue with a beam of infrared monochromatic light;

b) measuring the number of Raman bands produced thereby in the Raman spectral region from 700 to 1900 cm^-1 ; and

c) comparing said number of Raman bands measured with the number of Raman bands correspondingly measured from known samples of malignant tumor tissue, benign tumor tissue, and benign or normal tissue for the same type of tissue being tested.

6. The method of claim 5 wherein the tissue being tested is human breast tissue and wherein the number of bands is four Raman bands for benign or normal human breast tissue, three Raman bands for benign human breast tumor tissue, and two Raman bands for malignant human breast tumor tissue.

7. A method of determining if a human breast tissue sample is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue comprising the steps of:

a) irradiating the human breast tissue sample with a beam of infrared monochromatic light;

b) measuring for the presence of Raman bands at a Raman shift of about 1078, 1240, and 1300 cm^-1 ;

c) whereby the absence of Raman bands at a Raman shift of about 1078, 1240, and 1300 cm^-1 indicates that the human breast tissue sample is a malignant tumor tissue, the presence of a Raman band at a Raman shift of about 1240 cm^-1 and the absence of Raman bands at a Raman shift of about 1078 and 1300 cm^-1 indicates that the human breast tissue sample is a benign tumor tissue, and the presence of Raman bands at a Raman shift of about 1078 and 1300 cm^-1 and the absence of a Raman band at a Raman shift of about 1240 cm^-1 indicates that the human breast tissue sample is a normal or benign tissue.

8. A method for use in determining if a tissue of human breast is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue comprising the steps of:

a) irradiating the tissue with a beam of infrared monochromatic light producing thereby an infrared Raman spectrum having a first band at 1445±

4 cm^-1 and a second band at a wavenumber selected from the group consisting of 1651±

4 cm^-1 ;

b) measuring the intensity of said first and second Raman bands so produced;

c) calculating the ratio of said intensities; and

d) comparing said ratio to the ratio correspondingly obtained for the same two Raman bands from known samples of malignant human breast tumor tissue, benign human breast tumor tissue, and normal or benign human breast tissue.

9. An apparatus for use in determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue comprises:

a) means for producing an infrared monochromatic beam of light;

b) an endoscope comprising means for transmitting the infrared monochromatic beam of light to the tissue and means for collecting the Raman scattered light from the tissue;

c) means, coupled to said collecting means, for producing a Raman spectrum for the tissue;

d) means for comparing the Raman spectrum for the tissue being tested to standard Raman spectra for malignant tumor tissue, benign tumor tissue, and normal or benign tissue for the same type of tissue being tested; and

e) means for displaying the result of the comparison.

10. The apparatus of claim 9 wherein said means for producing an infrared monochromatic beam of light comprises a laser selected from the group consisting of semiconductor lasers, fosterite lasers, YAG lasers, Ti sapphire lasers, alexandrite lasers, emerald lasers, GGSG lasers, and dye lasers.

11. An apparatus for determining if human breast tissue is malignant tumor tissue, benign tumor tissue, or normal or benign tissue comprising:

a) means for producing an infrared monochromatic beam of light;

b) an endoscope comprising means for transmitting the infrared monochromatic beam of light to the human breast tissue and means for collecting the Raman scattered light from the human breast tissue;

c) means, coupled to said collecting means, for detecting the presence of Raman bands at a Raman shift of about 1078, 1240, and 1300 cm^-1 ; and

d) means for indicating that the human breast tissue is malignant tumor tissue if no Raman bands are detected at a Raman shift of about 1078, 1240, and 1300 cm^-1, is benign tumor tissue if a Raman band is detected at a Raman shift of about 1240 cm^-1 but not at a Raman shift of about 1078 and 1300 cm^-1, and is normal or benign tissue if Raman bands are detected at a Raman shift of about 1078 and 1300 cm^-1 but not at a Raman shift of 1240 cm^-1.

12. The apparatus of claim 11 wherein said means for producing an infrared monochromatic beam of light comprises a laser selected from the group consisting of semiconductor lasers, fosterite lasers, YAG lasers, Ti sapphire lasers, alexandrite lasers, emerald lasers, GGSG lasers, and dye lasers.

13. An apparatus for use in determining if a human breast tissue is a malignant human breast tumor breast tumor tissue, a benign human breast tumor tissue, or a normal or benign human breast tissue comprising:

a) means for producing an infrared monochromatic beam of light;

b) an endoscope comprising means for transmitting the infrared monochromatic beam of light to the human breast tissue and means for collecting the Raman scattered light from the human breast tissue said Raman scattered light including a first band at 1445±

4 cm^-1 and a second band at a wavenumber selected from the group consisting of 1651±

4 cm^-1 and 1659±

4 cm^-1 ;

c) means, coupled to said collecting means, for detecting the intensity of light at said first and said second bands;

d) means for calculating the ratio of said intensities;

e) means for comparing said ratio to ratios correspondingly obtained from known samples of malignant human breast tumor tissue, benign human breast tumor tissue, and normal or benign human breast tissue; and

f) means for displaying the result of the comparison.

14. The apparatus of claim 13 wherein said means for producing an infrared monochromatic beam of light comprises a laser selected from the group consisting of semiconductor lasers, fosterite lasers, YAG lasers, Ti sapphire lasers, alexandrite lasers, emerald lasers, GGSG lasers, and dye lasers.

15. An apparatus for use in determining if a tissue is a malignant tumor tissue, a benign tumor tissue, or a normal or benign tissue comprising:

a) means for producing a beam of infrared monochromatic light;

b) an endoscope comprising means for transmitting the infrared monochromatic beam of light to the tissue and means for collecting the Raman scattered light from the tissue over the spectral region from about 700 to 1900 cm^-1 ;

c) means, coupled to said collecting means, for measuring the number of Raman bands present in the Raman scattered light;

d) means for comparing the number of Raman bands present in the Raman scattered light with standards obtained from known samples of malignant tumor tissue, benign tumor tissue, and normal or benign tissue for the same type of tissue being tested; and

e) means for displaying the result of the comparison.

16. The apparatus of claim 15 wherein said means for producing an infrared monochromatic beam of light comprises a laser selected from the group consisting of semiconductor lasers, fosterite lasers, YAG lasers, Ti sapphire lasers, alexandrite lasers, emerald lasers, GGSG lasers, and dye lasers.