# US 5,348,018 A · Method for determining if tissue is malignant as opposed to non-malignant using time-resolved fluorescence spectroscopy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,348,018 A - Document ID: US5348018A - Status: Granted - Kind: A - Application number: 07/797,723 - Filed: 1991-11-25 - Granted: 1994-09-20 - Earliest claimed: 1991-11-25 - Inventors: Robert R. Alfano; Asima Pradhan; Guichen C. Tang; Leming Wang; Yury Budansky; Bidyut Baran Das - Web page: https://patentgrep.com/patent/US5348018A ## CPC - G01N 21/6486: {Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence)} - A61B 5/0071: {by measuring fluorescence emission} - A61B 5/0084: {for introduction into the body, e.g. by catheters (A61B5/1459 takes precedence)} - A61B 5/0091: {for mammography} - A61B 5/4312: {Breast evaluation or disorder diagnosis (optical mammography A61B5/0091)} - B23K 26/0624: {using ultrashort pulses, i.e. pulses of 1 ns or less} - G01N 21/6408: {with measurement of decay time, time resolved fluorescence} - A61B 5/0075: {by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy (A61B5/0071 takes precedence)} - A61B 5/0086: {using infrared radiation} - G01N 2021/6417: {Spectrofluorimetric devices} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - B23K: SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM ## 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)=A.sub.1 e(-t/.tau..sub.1)+A.sub.2 e(-t/.tau..sub.2) one can quantify the differences between tissues of various conditions. For example, non-malignant human breast tissues exhibit a slow component (.tau..sub.2) which is less than 1.6 ns whereas malignant human breast tissues exhibit a slow component (.tau..sub.2) which is greater than 1.6 ns. In addition, non-malignant human breast tissues exhibit a ratio of fast to slow amplitudes (A.sub.1 /A.sub.2) which is greater than 0.85 whereas malignant human breast tissues exhibit a ratio of fast to slow amplitudes (A.sub.1 /A.sub.2) 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 ### Claim 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. ### Claim 2 (depends on 1) 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. ### Claim 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 .tau..sub.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. ### Claim 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 A.sub.1 /A.sub.2 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. ### Claim 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. ### Claim 6 (depends on 5) 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. ### Claim 7 (depends on 5) 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. ### Claim 8 (depends on 5) The method as claimed in claim 5 wherein the native time-resolved fluorescence is measured at about 450 nm. ### Claim 9 (depends on 5) 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. ### Claim 10 (depends on 5) The method as claimed in claim 5 wherein the tissue sample is human breast tumor tissue. ### Claim 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 .tau..sub.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. ### Claim 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 .tau..sub.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. ### Claim 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. ### Claim 14 (depends on 13) 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. ### Claim 15 (depends on 13) The method as claimed in claim 13 wherein the native time-resolved fluorescence is measured at about 600 nm. ### Claim 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 .tau..sub.1 is about 100 ps whereby the tissue sample is malignant or about 200 ps whereby the tissue sample is normal.