Systems and methods for spectral analysis of a tissue mass using an instrument, an optical probe, and a Monte Carlo or a diffusion algorithm

• US 9,820,655 B2
• Filed: 09/29/2008
• Issued: 11/21/2017
• Est. Priority Date: 09/28/2007
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Ramanujam, Nirmala, Yu, Bing, Brown, Jonathon Quincy
• Primary Examiner(s): Gupta, Vani
• Application Number:
  US12/680,305
• Publication Number:
  US 20110112435A1
• Time in Patent Office: 3,340 Days
• Field of Search: 600407-480
• 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 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: A61B 5/4312 Breast evaluation or disorder diagnosis A61B5/0091 takes precedence

Abstract

Systems and methods for spectral analysis of a tissue mass using an instrument, an optical probe, and a Monte Carlo algorithm or a diffusion algorithm are provided. According to one method, an instrument is inserted into a tissue mass. A fiber optic probe is applied via the instrument into the tissue mass. Turbid spectral data of the tissue mass is measured using the fiber probe. The turbid spectral data is converted to absorption, scattering, and/or intrinsic fluorescence spectral data via a Monte Carlo algorithm or diffusion algorithm. Biomarker concentrations in the tissue mass are quantified using the absorption, scattering, and/or intrinsic fluorescence spectral data.

Claims

1. A system for determining biomarker concentrations in a tissue mass, the system comprising:

an instrument for inserting into the tissue mass;

a fiber optic probe for interfacing the tissue mass upon being inserted into the instrument and measuring turbid spectral data of the tissue mass, wherein measuring the turbid spectral data includes conducting fluorescence spectral measurements and diffuse reflectance measurements of the tissue mass simultaneously, wherein the fiber optic probe is a forward firing fiber optic probe that includes a probe tip comprising a plurality of centrally grouped illumination fibers that are concentrically surrounded by a plurality of collection fiber rings, wherein each of the collection fiber rings consists of a plurality of ring-specific collection fibers or a plurality of ring-specific collection fibers and a plurality of dead fibers; and

a processing unit for converting the turbid spectral data to absorption, scattering, and intrinsic fluorescence spectral data via a Monte Carlo algorithm or a diffusion algorithm and quantifying biomarker concentrations in the tissue mass using the absorption, scattering, and intrinsic fluorescence spectral data, wherein the intrinsic fluorescence spectral data is corrected to account for the absorption and scattering data.

2. The system of claim 1 wherein the fiber optic probe fits within a biopsy needle or a biopsy cannula.

3. The system of claim 2 wherein the biopsy needle includes at least one of a Suros 9G biopsy needle, a Mammotome biopsy needle, a Bard Vacora 10G biopsy needle, a Bard Vacora 14G biopsy needle, and a Cardinal Achieve 14G biopsy needle.

4. The system of claim 1 wherein the instrument comprises a cannula, a biopsy needle, an endoscopic instrument, and a laparoscopic instrument.

5. The system of claim 1 wherein the turbid spectral data comprises diffuse reflectance spectral data and fluorescence spectral data of the tissue mass.

6. The system of claim 1 wherein the biomarker concentrations are used to determine if the tissue mass is malignant, benign, or normal, or are used to quantify drug uptake by the tissue mass.

7. The system of claim 6 wherein a biopsy is conducted on the tissue mass through a cannula or a biopsy needle if the tissue is malignant.

8. The system of claim 1 wherein the fiber optic probe is adapted to acquire the turbid spectral data using a spectrometer having a spectral bandpass of between about 2.5 nm and 5 nm.

9. The system of claim 1 wherein the Monte Carlo algorithm includes either an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm.

10. The system of claim 1 wherein the processing unit is further configured to determine the concentrations at least one of total hemoglobin, oxyhemoglobin concentration, deoxyhemoglobin concentration, beta carotene concentration, hemoglobin saturation, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), collagen, porphyrins, retinol, tryptophan, tissue blood loss, dilutional effects of fluids, in vivo.

11. A method for determining biomarker concentrations in a tissue mass, the method comprising:

inserting an instrument into the tissue mass;

applying a fiber optic probe upon being inserted into the instrument into the tissue mass, wherein the fiber optic probe is a forward firing fiber optic probe that includes a probe tip comprising a plurality of centrally grouped illumination fibers that are concentrically surrounded by a plurality of collection fiber rings, wherein each of the collection fiber rings consists of a plurality of ring-specific collection fibers or a plurality of ring-specific collection fibers and a plurality of dead fibers;

measuring turbid spectral data of the tissue mass using the fiber optic probe, wherein measuring the turbid spectral data includes conducting fluorescence spectral measurements and diffuse reflectance measurements of the tissue mass simultaneously;

converting the turbid spectral data to absorption, scattering, and intrinsic fluorescence spectral data via a Monte Carlo algorithm or a diffusion algorithm; and

quantifying biomarker concentrations in the tissue mass using the at least one of absorption, scattering, and intrinsic fluorescence spectral data, wherein the intrinsic fluorescence spectral data is corrected to account for the absorption and scattering data.

12. The method of claim 11 wherein the fiber optic probe is adapted to fit within a biopsy needle or a biopsy cannula.

13. The method of claim 12 wherein the biopsy needle includes at least one of a Suros 9G biopsy needle, a Mammotome biopsy needle, a Bard Vacora 10G biopsy needle, a Bard Vacora 14G biopsy needle, and a Cardinal Achieve 14G biopsy needle.

14. The method of claim 11 wherein the instrument comprises a cannula, a biopsy needle, an endoscopic instrument, and a laparoscopic instrument.

15. The method of claim 11 wherein the turbid spectral data comprises diffuse reflectance spectral data and fluorescence spectral data of the tissue mass.

16. The method of claim 11 wherein the biomarker concentrations are used to determine if the tissue mass is malignant, benign, or normal, or are used to quantify drug uptake by the tissue mass.

17. The method of claim 16 wherein a biopsy is conducted on the tissue mass through a cannula or a biopsy needle if the tissue is malignant.

18. The method of claim 11 wherein the fiber optic probe is adapted to acquire the turbid spectral data using a spectrometer having a spectral bandpass of between about 2.5 nm and 5 nm.

19. The method of claim 11 wherein the Monte Carlo algorithm includes either an inverse Monte Carlo reflectance algorithm or an inverse Monte Carlo fluorescence algorithm.

20. The method of claim 11 further comprising:

applying a contrast agent to the tissue mass to enhance light scattering, absorption, or fluorescence in the tissue mass.

21. The method of claim 20 wherein the enhanced light scattering, absorption, or fluorescence aids with margin assessment.

22. The method of claim 20 wherein the contrast agent includes at least one of acetic acid, Acriflavin, 2-2-deoxy-D-glucose (NBDG), fluorescin, aminolevulinic acid, and methylene blue.

23. The method of claim 11 wherein the processing unit is further configured to determine the concentrations at least one of total hemoglobin, oxyhemoglobin concentration, deoxyhemoglobin concentration, beta carotene concentration, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), collagen, retinol, porphyrin, hemoglobin saturation, tissue blood loss, dilutional effects of fluids in vivo.