System and method for differentiation of normal and malignant in vivo liver tissues

• US 7,979,107 B2
• Filed: 08/06/2009
• Issued: 07/12/2011
• Est. Priority Date: 07/05/2002
• Status: Expired due to Fees

• Current Assignee: Cleveland Clinic Foundation, Vanderbilt University
• Original Assignee: Cleveland Clinic Foundation, Vanderbilt University
• Inventors: Lin, Wei-Chiang, Toms, Steven A., Chari, Ravi S., Mahadevan-Jansen, Anita
• Primary Examiner(s): Casler; Brian
• Assistant Examiner(s): Kish; James
• Application Number:
  US12/537,008
• Publication Number:
  US 20090292211A1
• Time in Patent Office: 705 Days
• Field of Search: 600/407, 600/473, 600/476, 356/73, 356/318
• US Class Current: 600/407
• 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 5/4244 liver

Abstract

A method for differentiating malignant in vivo liver tissues from normal in vivo liver tissues of a living subject includes the steps of: (a) illuminating a first area and a second area of in vivo liver tissues of the living subject with a first excitation light, (b) measuring an intensity of fluorescent light emitted from each of the first area and the second area of in vivo liver tissues in response to the first excitation light as a function of wavelength so as to obtain a first and a second fluorescent spectra, respectively, (c) illuminating the first area and the second area of in vivo liver tissues with a second excitation light, (d) measuring an intensity of diffuse light reflected by each of the first area and the second area of in vivo liver tissues in response to the second excitation light as a function of wavelength so as to obtain a first and a second diffused reflectance spectra, respectively, and (e) identifying one of the first area and the second area of in vivo liver tissues as malignant liver tissues and the other one of the first area and the second area of in vivo liver tissues as normal liver tissues, by comparing the first fluorescence spectrum and the second florescence spectrum, and comparing the first diffused reflection spectrum and the second diffused reflection spectrum.

Claims

1. A method for differentiating malignant in vivo liver tissues from normal in vivo liver tissues of a living subject, comprising the steps of:

(a) illuminating a first area and a second area of in vivo liver tissues of the living subject with a first excitation light;

(b) measuring an intensity of fluorescent light emitted from the first area of in vivo liver tissues and an intensity of fluorescent light emitted from the second area of in vivo liver tissues in response to the first excitation light as a function of wavelength so as to obtain a first and a second fluorescent spectra of the in vivo liver tissues of the first area and the second area, respectively;

(c) illuminating the first area and the second area of in vivo liver tissues of the living subject with a second excitation light;

(d) measuring an intensity of diffuse light reflected by the first area of in vivo liver tissues and an intensity of diffuse light reflected by the second area of in vivo liver tissues in response to the excitation light as a function of wavelength so as to obtain a first and a second diffused reflectance spectra of the in vivo liver tissues of the first area and the second area, respectively; and

(e) identifying one of the first area and the second area of in vivo liver tissues as malignant liver tissues and the other one of the first area and the second area of in vivo liver tissues as normal liver tissues, by identifying corresponding blood absorption signature through comparing the first fluorescence spectrum of the in vivo liver tissues of the first area and the second florescence spectrum of the in vivo liver tissues of the second area, and comparing the first diffused reflectance spectrum of the in vivo liver tissues of the first area and the second diffused reflectance spectrum of the in vivo liver tissues of the second area, wherein the fluorescence spectrum of the malignant liver tissues shows no blood absorption signature at a first wavelength of about 540 nm and a second wavelength of about 580 nm, and the intensity of the diffused reflectance spectrum of the malignant liver tissues substantially monotonically decreases over a wavelength region from about 620 nm to about 700 nm, and the fluorescence spectrum of the normal liver tissues shows blood absorption signature at the first wavelength of about 540 nm and the second wavelength of about 580 nm, and the intensity of the diffused reflectance spectrum of the normal liver tissues is substantially unchanged over the wavelength region from about 620 nm to about 700 nm, wherein the blood absorption signature in the fluorescence spectrum of the normal liver tissues corresponds to spectral valleys at the first wavelength of about 540 nm and the second wavelength of about 580 nm.

2. The method of claim 1, wherein the malignant liver tissues are identified as primary liver tumor tissues when the intensity of the fluorescence spectrum of the malignant liver tissues is at least three times larger than the intensity of the fluorescence spectrum of the normal liver tissues over a wavelength range of about 400 nm to about 600 nm.

3. The method of claim 1, wherein the malignant liver tissues are identified as secondary liver tumor tissues when the fluorescence spectrum of the malignant liver tissues has a first peak at a wavelength of about 400 nm and a second peak at a wavelength of about 480 nm, and a ratio of a corresponding first peak intensity to a corresponding second peak intensity is substantially about one.

4. The method of claim 1, wherein the first excitation light is substantially monochromatic and has a dominant wavelength between about 320 nm and about 340 nm.

5. The method of claim 1, wherein the second excitation light is substantially white light.

6. An apparatus for differentiating malignant in vivo liver tissues from normal in vivo liver tissues of a living subject, comprising:

(a) a first light source adapted for emitting a first excitation light;

(b) a second light source adapted for emitting a second excitation light;

(c) a fiber optical probe coupled with the first light source and the second light source and configured to deliver the first excitation light and the second excitation light to a first area of in vivo liver tissues of the living subject in a first instance, and to deliver the first excitation light and the second excitation light to a second area of in vivo liver tissues of the living subject in a second instance;

(d) a detector coupled with the fiber optical probe and configured to receive fluorescent light emitted from and diffuse light reflected by the first area of in vivo liver tissues of the living subject in response to the first excitation light and the second excitation light, respectively, in the first instance, and to measure an intensity of the fluorescent light emitted from the first area as a function of wavelength, and an intensity of the diffuse light reflected by the first area as a function of wavelength, so as to obtain a first fluorescent spectrum of the first area, and a first diffused reflectance spectrum of the first area, respectively, the detector is further configured to receive fluorescent light emitted from and diffuse light reflected by the second area of the living subject in response to the first excitation light and the second excitation light, respectively, in the second instance, and to measure an intensity of the fluorescent light emitted from the second area as a function of wavelength, and an intensity of the diffuse light reflected by the second area as a function of wavelength, so as to obtain a second fluorescent spectrum of the second area, and a second diffused reflectance spectrum of the second area, respectively; and

(e) a controller coupled with the detector and programmed to identify corresponding blood absorption signature through comparing the first fluorescence spectrum of the in vivo liver tissues of the first area and the second fluorescence spectrum of the in vivo liver tissues of the second area, and to compare the first diffused reflectance spectrum of the in vivo liver tissues of the first area and the second diffused reflectance spectrum of the in vivo liver tissues of the second area, so as to identify one of the first area and the second area of in vivo liver tissues as malignant liver tissues and the other one of the first area and the second area of in vivo liver tissues as normal liver tissues, wherein the fluorescence spectrum of the malignant liver tissues does not show blood absorption signature at a first wavelength of about 540 nm, and at a second wavelength of about 580 nm, and the intensity of the diffused reflectance spectrum of the malignant tissues substantially monotonically decreases over a wavelength region from about 620 nm to about 700 nm, and the fluorescence spectrum of the normal liver tissues shows blood absorption signature at the first wavelength of about 540 nm and the second wavelength of about 580 nm, and the intensity of the diffused reflectance spectrum of the normal liver tissues is substantially unchanged over the wavelength region from about 620 nm to about 700 nm, wherein the blood absorption signature in the fluorescence spectrum of the normal liver tissues corresponds to spectral valleys at the first wavelength of about 540 nm and the second wavelength of about 580 nm.

7. The apparatus of claim 6, wherein the first light source comprises a laser, and the first excitation light has substantially a wavelength between about 320 nm and about 340 nm.

8. The apparatus of claim 6, wherein the second light source comprises a halogen light source.

9. The apparatus of claim 6, wherein the detector comprises a spectrometer.

10. The apparatus of claim 6, wherein the controller comprises a computer.