Method for quantitative measurement of fluorescent and phosphorescent drugs within tissue utilizing a fiber optic probe

• US 6,377,842 B1
• Filed: 08/23/1999
• Issued: 04/23/2002
• Est. Priority Date: 09/22/1998
• Status: Expired due to Fees

• Current Assignee: Aurora Optics, Inc.
• Original Assignee: Aurora Optics, Inc.
• Inventors: Pogue, Brian William, Burke, Gregory Charles
• Primary Examiner(s): Lateef, Marvin M.
• Assistant Examiner(s): JAMES, TALAYA G
• Application Number:
  US09/379,001
• Time in Patent Office: 974 Days
• Field of Search: 600/476, 600/478, 600/473, 600/310, 600/312, 600/329, 600/342, 250/458.1, 250/459.1, 356/317, 436/172
• US Class Current: 600/478
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/7242 using integration
• CPC Class Codes: A61N 5/0601 Apparatus for use inside the body
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent

Abstract

A fiber optic based probe has been designed to sample the fluorescence or phosphorescence signal from animal or human tissues, such that the light intensity is not multiply scattered. This type of measurement allows a linear detection of the concentration of the luminescent compound non-invasively from the tissue. The basic principle of the fiber probe is to use fiber optics which are smaller in diameter that the average scattering length of the tissue. In order to increase the detected signal to a stronger level, multiple fibers are used by spacing them out on the surface of the tissue so that each fiber samples an isolated section of tissue. Each fiber delivers the excitation light to the tissue, and receives the emission light from the tissue. All fibers are coupled into the same detector to integrate the overall signal. Sampling of the scattered excitation signal intensity is also done to correct for changes in the scattering coefficient between tissues. This fiber bundle can be used to quantify the concentration of fluorescence or phosphorescent chemicals in vivo non-invasively. One application of this device is as a dosimetry tool, to monitor photosensitizer drug concentration within tissue for photodynamic therapy.

Claims

1. A method for detecting fluorescence or phosphorescence signals from a tissue sample containing a fluorophore or phosphor concentration therein, the method comprising the steps of:

providing an optic probe for detecting luminescence from a tissue sample containing a fluorophore or phosphor concentration therein, the optic probe having a plurality of optic fibers maintained in a bundle, each of the plurality of optic fibers having,

a first end where the fibers are arranged in a substantially contiguous array and collectively form a first bundle end, and

a tissue contact end where the fibers are arranged in a spaced apart arrangement at a substantially constant minimal spacing between near neighbor fibers, the spaced apart arrangement forming a tissue contact bundle end for placement against the tissue sample;

aligning the first bundle end with an optical detection device;

placing the tissue contact bundle end with a site on the tissue sample;

passing an excitation light through the optic fibers; and

,

monitoring fluorescence or phosphorescence transmitted through the optic fibers from the tissue sample with the optical detection device.

2. A method for detecting fluorescence or phosphorescence signals from a tissue sample containing a fluorophore or phosphor concentration therein, the method comprising the steps of:

providing a plurality of optic probes, each optic probe having a plurality of optic fibers maintained in a bundle, each of the plurality of optic fibers having,

a first end where the fibers are arranged in a substantially contiguous array and collectively form a first bundle end, and

a tissue contact end where the fibers are arranged in a spaced apart arrangement at a substantially constant minimal spacing between near neighbor fibers, the spaced apart arrangement forming a tissue contact bundle end for placement against the tissue sample;

aligning the first bundle end of each of the plurality of optic probes to an optical detection device;

placing the tissue contact bundle end of each of the plurality of optic probes with the tissue sample;

passing an excitation light through the optic fibers;

monitoring fluorescence or phosphorescence signals transmitted through the fibers of each of the optic probes from the tissue sample with the optical detection device; and

,

integrating said fluorescence or phosphorescence signals.

3. An optic probe for detecting luminescence from a tissue sample containing a fluorophore or phosphor concentration therein, the optic probe comprising:

a plurality of optical fibers maintained in a bundle, each of said plurality of optic fibers having,

a first end where said fibers are arranged in a substantially contiguous array and collectively form a first bundle end, and

a tissue contact end where said fibers are arranged in a spaced apart arrangement at a substantially constant minimal spacing between near neighbor fibers, said spaced apart arrangement forming a tissue contact bundle end for placement against the tissue sample.

4. The optic probe of claim 3 wherein said bundle of a plurality of optic fibers is generally arranged circular in cross-section.

5. The optic probe of claim 3 wherein said plurality of optic fibers ranges from 2 optic fibers to 500 optic fibers.

6. The optic probe of claim 5 wherein said plurality of optic fibers ranges from 10 optic fibers to 100 optic fibers.

7. The optic probe of claim 6 wherein said plurality of optic fibers is about 30 optic fibers.

8. The optic probe of claim 3 wherein said optic fibers have diameters ranging from 10 microns to 500 microns.

9. The optic probe of claim 8 wherein said diameters range from 10 microns to 200 microns.

10. The optic probe of claim 9 wherein said diameters are about 100 microns.

11. The optic probe of claim 3 wherein one of said plurality of optical fibers is separated from said bundle at said first end.

12. The optic probe of claim 3 wherein said substantially constant minimal spacing separating said near neighbor fibers at said tissue contact bundle end of said bundle ranges from 300 microns to 2,000 microns (2 mm).

13. The optic probe of claim 12 wherein said substantially constant minimal spacing separating said near neighbor fibers at said tissue contact bundle end of said bundle is about 1,000 microns (1 mm).