Monte Carlo based model of fluorescence in turbid media and methods and systems for using same to determine intrinsic fluorescence of turbid media

• US 7,818,154 B2
• Filed: 03/16/2007
• Issued: 10/19/2010
• Est. Priority Date: 03/17/2006
• Status: Active Grant

• Current Assignee: Duke University
• Original Assignee: Duke University
• Inventors: Palmer, Gregory M., Ramanujam, Nirmala
• Primary Examiner(s): Zeman; Mary K
• Application Number:
  US11/725,141
• Publication Number:
  US 20070232932A1
• Time in Patent Office: 1,313 Days
• Field of Search: 703/11, 707/102, 702/19, 356/244, 422/67, 422/82, 422/86, 436/172
• US Class Current: 703/11
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/6417 Spectrofluorimetric devices
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

The subject matter described herein includes a method for modeling fluorescence in turbid media and methods and systems for using the model to determine intrinsic fluorescence of turbid media. According to one aspect, a method for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium is provided. The method includes illuminating a turbid medium of interest with an electromagnetic radiation source using a probe of a particular geometry and detecting measured fluorescence for the turbid medium using the probe. At least one set of Monte Carlo simulations is run to determine an escape energy probability map and an absorbed energy density map for the turbid medium. An indication of the intrinsic fluorescence of the turbid medium is determined using the escape probability density map and the absorbed energy density map in a manner that accounts for the geometry of the probe.

Claims

1. A method for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium, the method comprising:

illuminating a turbid medium of interest with an electromagnetic radiation source using a probe of a particular geometry that comprises one or more collection fibers and one or more illumination fibers and detecting measured fluorescence for the turbid medium using the probe;

running at least one set of Monte Carlo simulations to determine an escape energy probability map and an absorbed energy density map for the turbid medium; and

determining, in a manner that accounts for the geometry of the probe using a function that considers the surface areas of the one or more collection fibers and the one or more illumination fibers of the probe and photons escaping the turbid medium, and using the measured fluorescence, the absorbed energy density map, and the escape energy probability map, an indication of intrinsic fluorescence of the turbid medium.

2. The method of claim 1 wherein running at least one set of Monte Carlo simulations includes:

running a single set of Monte Carlo simulations where photons are launched from varying depths in a turbid medium with an arbitrary set of optical properties to determine an escape energy probability map for the medium with the arbitrary set of optical properties;

scaling the escape energy probability map for the medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the escape energy probability map for the medium of interest; and

using a reciprocity principle to determine the absorbed energy density map for the medium of interest.

3. The method of claim 1 wherein running at least one set of Monte Carlo simulations includes:

running a first set of Monte Carlo simulations where photons are launched from outside of a turbid medium with an arbitrary set of optical properties to determine an absorbed energy density map for the medium with the arbitrary set of optical properties and scaling the absorbed energy density map for the turbid medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the absorbed energy density map for the medium of interest; and

running a second set of Monte Carlo simulations where photons are launched from varying depths in the turbid medium with the arbitrary set of optical properties to determine an escape energy probability map for the medium with the arbitrary set of optical properties and scaling the escape energy probability map for the medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the escape energy probability map for the medium of interest.

4. The method of claim 1 wherein determining the intrinsic fluorescence of the medium includes determining a product of a quantum yield and the concentration of at least one known fluorophore.

5. The method of claim 1 wherein determining the intrinsic fluorescence of the medium in the medium includes determining the concentration of at least one known fluorophore in the medium.

6. The method of claim 1 wherein determining an indication of the intrinsic fluorescence of the medium includes determining the indication of the intrinsic fluorescence as a function of a scaling factor that accounts for a difference in magnitude between the at least one Monte Carlo simulation and the measured fluorescence.

7. The method of claim 1 wherein determining an indication of the intrinsic fluorescence of the medium accounting for the geometry of the probe includes determining the indication of the intrinsic fluorescence in a manner such that the indication will be the same for the turbid medium when fluorescence is measured with different probe geometries.

8. The method of claim 1 wherein determining an indication of the intrinsic fluorescence accounting for geometry of the probe includes determining a probability that a photon exiting the medium of interest will be detected by the probe given the geometry of the probe.

9. The method of claim 8 wherein determining the probability includes convolving photons generated by a point source during the at least one simulation with illumination and collection areas of the probe.

10. The method of claim 1 wherein the turbid medium of interest comprises a biological tissue sample.

11. A system for modeling fluorescence of a turbid medium and for using the model to determine intrinsic fluorescence in the turbid medium, the system comprising:

a probe for illuminating a turbid medium of interest with electromagnetic radiation generated by an electromagnetic radiation source, the probe having a particular geometry that comprises one or more collection fibers and one or more illumination fibers and the probe detecting measured fluorescence for the turbid medium; and

a processor for running at least one set of Monte Carlo simulations to determine an escape energy probability map and an absorbed energy density map for the turbid medium, for determining, using the measured fluorescence, the absorbed energy density map, and the escape energy probability map, wavelength-dependent extinction coefficients and emission spectra for a known fluorophore, and accounting for the geometry of the probe using a function that considers the surface areas of the one or more collection fibers and the one or more illumination fibers of the probe and photons escaping the turbid medium, an indication of intrinsic fluorescence of the turbid medium.

12. The system of claim 11 wherein the processor is adapted to, in running at least one set of Monte Carlo simulations:

run a single set of Monte Carlo simulations where photons are launched from varying depths in a turbid medium with an arbitrary set of optical properties to determine an escape energy probability map for the medium with the arbitrary set of optical properties;

scale the escape energy probability map for the medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the escape energy probability map for the medium of interest; and

use a reciprocity principle to determine the absorbed energy density map for the medium of interest.

13. The system of claim 11 wherein, in running at least one set of Monte Carlo simulations, the processor is adapted to:

run a first set of Monte Carlo simulations where photons are launched from outside of a turbid medium with an arbitrary set of optical properties to determine an absorbed energy density map for the medium with the arbitrary set of optical properties and scale the absorbed energy density map for the turbid medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the absorbed energy density map for the medium of interest; and

run a second set of Monte Carlo simulations where photons are launched from varying depths in the turbid medium with the arbitrary set of optical properties to determine an escape energy probability map for the medium with the arbitrary set of optical properties and scale the escape energy probability map for the medium with the arbitrary set of optical properties using optical properties for the medium of interest to determine the escape energy probability map for the medium of interest.

14. The system of claim 11 wherein, in determining the intrinsic fluorescence of the medium, the processor is adapted to determine a product of a quantum yield and the concentration of at least one known fluorophore.

15. The system of claim 11 wherein, in determining the intrinsic fluorescence of the medium, the processor is adapted to determine the concentration of at least one known fluorophore in the medium.

16. The system of claim 11 wherein the processor is adapted to determine the intrinsic fluorescence as a function of a scaling factor that accounts for a difference in magnitude between the at least one Monte Carlo simulation and the measured fluorescence.

17. The system of claim 11 wherein the processor is adapted to determine the indication of the intrinsic fluorescence in a manner such that the indication of the intrinsic fluorescence will be the same for the turbid medium when fluorescence is measured with different probe geometries.

18. The system of claim 11 wherein the processor is adapted to determine a probability that a photon exiting the medium of interest will be detected by the probe given the geometry of the probe.

19. The system of claim 18 wherein, in determining the probability, the processor is adapted to convolve photons generated by a point source during at least one simulation with the illumination and collection areas of the probe.

20. The system of claim 11 wherein the turbid medium of interest comprises a biological tissue sample.