Method for determining if tissue is malignant as opposed to non-malignant using time-resolved fluorescence spectroscopy

• US 5,348,018 A
• Filed: 11/25/1991
• Issued: 09/20/1994
• Est. Priority Date: 11/25/1991
• Status: Expired due to Term

• Current Assignee: Mediscience Technology Corp. (Sensivida Medical Technologies, Inc.), The Research Foundation of State University of New York
• Original Assignee: Mediscience Technology Corp. (Sensivida Medical Technologies, Inc.)
• Inventors: Pradhan, Asima, Baran Das, Bidyut, Alfano, Robert R., Budansky, Yury, Wang, Leming, Tang, Guichen C.
• Primary Examiner(s): Cohen, Lee S.
• Assistant Examiner(s): Casler, Brian L.
• Application Number:
  US07/797,723
• Time in Patent Office: 1,030 Days
• Field of Search: 128/665, 128/633, 128/634, 606/3, 606/13, 606/10, 607/88, 607/89
• US Class Current: 600/476
• 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 5/0091 for mammography
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence
• CPC Class Codes: B23K 26/0624 using ultrashort pulses, i.e. pulses of 1ns or less
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

A method for determining if tissue is malignant as opposed to non-malignant (i.e., benign tumor tissue, benign tissue, or normal tissue), In one embodiment, the method comprises irradiating a human breast tissue sample with light at a wavelength of about 310 nm and measuring the time-resolved fluorescence emitted therefrom at about 340 nm. The time-resolved fluorescence profile is then compared to similar profiles obtained from known malignant and non-malignant human breast tissues. By fitting the profiles to the formula I(t)=A₁ e(-t/τ₁)+A₂ e(-t/τ₂) one can quantify the differences between tissues of various conditions. For example, non-malignant human breast tissues exhibit a slow component (τ₂) which is less than 1.6 ns whereas malignant human breast tissues exhibit a slow component (τ₂) which is greater than 1.6 ns. In addition, non-malignant human breast tissues exhibit a ratio of fast to slow amplitudes (A₁ /A₂) which is greater than 0.85 whereas malignant human breast tissues exhibit a ratio of fast to slow amplitudes (A₁ /A₂) which is less than 0.6. This technique can be used with different excitation and/or emission wavelengths, and can be applied to the detection of malignancies (or other abnormal states) in tissues other than human breast tissue.

Claims

1. A method for determining if a human breast tissue sample is malignant as opposed to non-malignant comprising:

a) irradiating the human breast tissue sample with a pulse of light at a wavelength of about 310 nm;

b) measuring a native time-resolved fluorescence emitted therefrom at a wavelength of about 340 nm; and

c) determining the condition of the human breast tissue sample in accordance with said measurement.

2. The method as claimed in claim 1 wherein said determining step comprises comparing the native time-resolved fluorescence emitted from the human breast tissue sample to that emitted from known malignment and non-malignment human breast tissues.

3. A method for determining if a human breast tissue sample is malignment as opposed to non-malignment comprising:

a) irradiating the human breast tissue sample with a pulse of light at a wavelength of about 310 nm;

b) measuring a native time-resolved fluorescence emitted therefrom at a wavelength of about 340 nm; and

c) determining the condition of the human breast tissue sample in accordance with said measurement wherein said determining step comprises fitting a profile of the native time-resolved fluorecence emitted from the human breast tissue sample to a double exponential of the formula ##EQU1## and determining if τ

₂ is less than 1.6 ns whereby the human breast tissue sample is non-malignant or greater than 1.6 ns whereby the human breast tissue sample is malignant.

4. A method for determining if a human breast tissue sample is malignant as opposed to non-malignant comprising:

a) irradiating the human breast tissue sample with a pulse of light at a wavelength of about 310 nm;

b) measuring a native time-resolved fluorescence emitted therefrom at a wavelength of about 340 nm; and

c) determining the condition of the human breast tissue sample in accordance with said measurement wherein said determining step comprising fitting a profile of the native time-resolved fluorescence emitted from the human breast tissue sample to a double exponential of the formula ##EQU2## and determining if A₁ /A₂ is greater than 0.85 whereby the human breast tissue sample is non-malignant or less than 0.6 whereby the human breast tissue sample is malignant.

5. A method for determining if a tissue sample selected from the group consisting of human breast tissue and human ovarian tissue is malignant as opposed to non-malignant comprising:

a) irradiating the tissue sample with light at a wavelength of about 353 nm;

b) measuring a native time-resolved fluorescence emitted therefrom over one or more wavelength in a spectral band from about 400 nm to about 500 nm; and

c) determining the condition of the tissue sample in accordance with said measurement.

6. The method as claimed in claim 5 wherein said determining step comprises comparing the native time-resolved fluorescence emitted from the tissue sample to that emitted from known malignant and non-malignant tissues of the same type of tissue.

7. The method as claimed in claim 5 wherein the tissue sample is human breast tissue and wherein the native time-resolved fluorescence is measured at about 400 nm.

8. The method as claimed in claim 5 wherein the native time-resolved fluorescence is measured at about 450 nm.

9. The method as claimed in claim 5 wherein the tissue sample is human breast tissue and wherein the native time-resolved fluorescence is measured at about 500 nm.

10. The method as claimed in claim 5 wherein the tissue sample is human breast tumor tissue.

11. A method for determining if a human breast tissue sample is malignant as opposed to non-malignant comprising:

a) irradiating the human breast tissue sample with a pulse of light at a wavelength of about 353 nm;

b) measuring a native-time resolved fluorescence emitted therefrom over one or more wavelengths in a spectral band from about 400 nm to about 500 nm; and

c) determining the condition of the human breast tissue sample in accordance with said measurement wherein said determining step comprises fitting a profile of the native time-resolved fluorescence emitted from the human breast tissue sample to a double exponential of the formula ##EQU3## and determining if τ

₁ is less than about 150 ps whereby the human breast tissue sample is malignant or greater than about 200 ps whereby the human breast tissue sample is non-malignant.

12. A method for determining if a human breast tissue sample is malignant as opposed to non-malignant comprising:

a) irradiating the human breast tissue sample with a pulse of light at a wavelength of about 353 nm;

b) measuring a native time-resolved fluorescent emitted therefrom over one or more wavelengths in a spectral band from about 400 nm to about 500 nm; and

c) determining the condition of the human breast tissue sample in accordance with said measurement wherein said determining step comprises fitting a profile of the native tissue-resolved fluorescence emitted from the human breast tissue sample to a double exponential of the formula ##EQU4## and determining if τ

₂ is greater than 2.4 ns whereby the human breast tissue sample is malignant or less than 2.4 ns whereby the human tissue sample is non-malignant.

13. A method for determining if a tissue sample selected from the group consisting of human breast tissue and human lung tissue is malignant as opposed to normal, said method comprising:

a) irradiating the tissue sample with light at a wavelength of about 530 nm;

b) measuring a native time-resolved fluorescence emitted therefrom over tone or more wavlengths in a spectral band from about 500 nm to about 600 nm; and

c) determining the condition of the tissue sample in accordance with said measurement.

14. The method as claimed in claim 13 wherein said determining step comprises comparing the native time-resolved fluorescence emitted from the tissue sample to that emitted from known malignment and normal tissues of the same type of tissue.

15. The method as claimed in claim 13 wherein the native time-resolved fluorescence is measured at about 600 nm.

16. A method for determine if a tissue sample selected from the group consisting of malignant tissue and normal tissue is malignant comprising:

a) irradiating the tissue sample with a pulse of light at a wavelength of about 530 nm;

b) measuring a native time-resolved fluorescence emitted therefrom over one or more wavlengths in a spectral band from about 550 nm to about 600 nm; and

c) determining the condition of the tissue sample in accordance with said measurement wherein said determining step comprises fitting a profile of the native time-resolved fluorescence emitted from the tissue sample to a double exponential of the formula ##EQU5## and determining if τ

₁ is about 100 ps whereby the tissue sample is malignant or about 200 ps whereby the tissue sample is normal.