IP Library Granted Patent US 7,865,230
Granted Patent B1
US 7,865,230 · App. 10/618,194 · Granted Jan 4, 2011

Method and system for detecting sentinel lymph nodes

Assignee: Texas A&M University System
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Quick Facts
Patent No.
US 7,865,230
App. No.
10/618,194
Granted
Jan 4, 2011
Kind
B1
Abstract

According to one embodiment of the present invention, a method for detecting lymph nodes in a human includes introducing a fluorescent contrast agent into a lymph node system of a body, directing near-infrared time-varying excitation light into the tissue of the body, causing the near-infrared time-varying excitation light to contact a lymph node of the lymphatic system, whereby a redshifted and time-varying emission light is generated, detecting the time-varying emission light at a surface of the body, filtering the time-varying emission light to reject excitation light re-emitted from the lymph node, and imaging the lymph node of the lymphatic system.

Claims (46)

1. Method for detecting lymph nodes in a human, comprising:

introducing a fluorescent contrast agent into a lymphatic system of a body;

directing time-varying excitation light into the tissue of the body;

causing the time-varying excitation light to contact a lymph node of the lymphatic system, whereby a time-varying emission light is generated, wherein the generated time-varying excitation light comprises a spatial distribution selected from the group consisting of a planar wave, a series of lines of illumination, concentric circles of illumination, and a ronchi rule pattern;

detecting the time-varying emission light at a surface of the body;

using frequency-domain photon migration, filtering light that is not time-varying;

filtering the time-varying emission light to reject excitation light re-emitted from the lymph node; and

imaging the lymph node of the lymphatic system.

2. The method of claim 1 , wherein introducing the fluorescent contrast agent comprises introducing indocyanine green (“ICG”).

3. The method of claim 1 , wherein directing time-varying excitation light into the tissue of the body comprises directing time-varying excitation light into the tissue of the body with a light source selected from the group consisting of a pulse, a series of pulses, pseudo random modulation, sinusoidally modulated light, and a square wave.

4. The method of claim 1 , wherein the spatial distribution is the ronchi rule pattern.

5. The method of claim 1 , further comprising modulating the excitation light to obtain a wavelength between approximately 700 nm and 900 nm.

6. The method of claim 1 , wherein causing the excitation light to contact a lymph node of the lymphatic system comprises causing the excitation light to contact a sentinel lymph node of the lymphatic system.

7. A system for detecting lymph nodes in a human, comprising:

a laser diode operable to direct time-varying near-infrared excitation light into the tissue of a body;

one or more optical components adapted to provide the time-varying near-infrared excitation light a spatial distribution selected from the group consisting of a planar wave, a series of lines of illumination, concentric circles of illumination, and a ronchi rule pattern;

an image intensifier operable to detect, at a surface of the body, a redshifted and time-varying emission light generated by the near-infrared time-varying excitation light contacting a lymph node of the lymphatic system;

one or more optical filters operable to reject excitation light re-emitted from the lymph node; and

an imaging apparatus operable to image the lymph node of the lymphatic system.

8. The system of claim 7 , further comprising a fluorescent contrast agent adapted to be injected into a lymphatic system of a body, the fluorescent contrast agent selected from the group consisting of a non-specific fluorescent contrast agent and a specific fluorescent contrast agent.

9. The system of claim 7 , wherein the spatial distribution is the ronchi rule pattern.

10. The system of claim 7 , further comprising a frequency generator to modulate the near-infrared time-varying excitation light to obtain a wavelength between approximately 700 nm and 900 nm.

11. The system of claim 7 , wherein the one or more optical filters are selected from the group consisting of a band pass filter, a long pass filter, and a holographic notch filter.

12. The system of claim 7 , wherein the one or more optical filters comprises any combination of the following filters: a band pass filter, a long pass filter, and a holographic notch filter.

13. The system of claim 7 , wherein the lymph node of the lymphatic system comprises a sentinel lymph node.

14. The system of claim 7 , wherein the imaging apparatus is a charge coupled device camera.

15. A method for detecting lymph nodes in a human, comprising:

introducing a fluorescent contrast agent into a lymphatic system of a body;

directing into the tissue of the body near-infrared time-varying excitation light modulated to obtain a wavelength between approximately 700 nm and 900 nm;

causing the near-infrared time-varying excitation light to contact a sentinel lymph node of the lymphatic system, whereby a redshifted and time-varying emission light is generated;

detecting the generated time-varying emission light at a surface of the body;

optically filtering the generated time-varying emission light to reject excitation light re-emitted from the sentinel lymph node;

quantitizing a fluorescence characteristic throughout at least a portion of the sentinel lymph node from the generated time-varying emission light by establishing a number of values with a processor, each of the values corresponding to a level of the fluorescence characteristic at a different position within the sentinel lymph node, the level of the fluorescence characteristic varying with a composition of the sentinel lymph node; and

imaging the sentinel lymph node in accordance with the values.

16. The method of claim 15 , wherein introducing the fluorescent contrast agent comprises introducing indocyanine green (“ICG”).

17. The method of claim 15 , wherein directing into the tissue of the body near-infrared time-varying excitation light comprises directing into the tissue of the body time-varying excitation light with a light source selected from the group consisting of a pulse, a series of pulses, pseudo random modulation, sinusoidally modulated light, and a square wave.

18. The method of claim 15 , wherein the fluorescence characteristic corresponds to at least one of fluorescence lifetime, fluorescence quantum efficiency, fluorescence yield, and fluorescence uptake.

19. The method of claim 15 , wherein quantitizing a fluorescence characteristic further comprises determining the values from a mathematical relationship modeling light scattering behavior of the portion of the sentinel lymph node.

20. The method of claim 19 , wherein the mathematical relationship corresponds to a diffusion equation approximation of multiply scattered light.

21. A method of lymph node analysis of humans, comprising:

exposing a lymph node to an excitation light with a pre-determined time varying intensity, the lymph node multiply scattering the excitation light;

detecting a multiply scattered light emission from the lymph node in response to said exposing;

determining a number of values from the emission with a processor, the values each corresponding to a level of a fluorescence characteristic at a different position within the lymph node, the level of the characteristic varying with lymph node composition; and

generating an image of lymph node compositional variation in accordance with the values.

22. The method of claim 21 , wherein exposing the lymph node to an excitation light comprises exposing the lymph node to a near-infrared time-varying excitation light.

23. The method of claim 21 , wherein the fluorescence characteristic corresponds to at least one of fluorescence lifetime, fluorescence quantum efficiency, fluorescence yield, and fluorescence uptake.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jan 4, 2018
From: TEXAS A&M UNIVERSITY SYSTEM
To: NIH - DEITR
Reel/Frame 045004/0921 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2003
From: SEVICK-MURACA, EVA M.; GURFINKEL, MICHAEL
To: TEXAS A&M UNIVERSITY SYSTEM, THE
Reel/Frame 014690/0406 →
Continuity (3)
Continuation In Part 0987014400 · May 30, 2001
Continuation 0936714800
Provisional Application 6003931800 · Feb 7, 1997