Devices and systems for fluorescence imaging of tissue

Patent metadata

Field	Value
Publication number	US-10154785-B2
Application number	US-201314373014-A
Country	US
Kind code	B2
Filing date	Jan 18, 2013
Priority date	Jan 18, 2012
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

A system and method for fluorescence imaging of tissue in vivo and in situ, e.g., for minimally invasive diagnosis of patients. A fluorescent imaging system is provided that has a dye carrier coupled to the distal end of a probe containing a fiber optics bundle, which allows for the introduction of at least one fluorescent dye therein the dye carrier into a portion of the tissue of interest of a subject or patient when the dye carrier is selectively brought into contact with the portion of the tissue of interest. The resulting fluorescence images permit the acquisition of diagnostic information on the progression of diseases at cellular/tissue level in patients.

First claim

What is claimed is:

1. A device comprising:
a probe defining a central bore, the probe having an outer surface, a distal end, an opposed proximal end, and a longitudinal axis extending between the distal end and the proximal end of the probe, the distal end defining a distal tip configured to contact a selected tissue of a subject, the outer surface of the probe extending away from the distal tip in a proximal direction and defining an outer diameter of the probe along a longitudinal length of the probe, the probe comprising:
image transmission means positioned therein the central bore of the probe and configured for communication with a light source; and
an objective lens positioned therein the central bore of the probe proximate the distal tip of the probe; and

an annular dye carrier comprising an open-cell polymer foam filled at least partially with a hydrogel, the dye carrier being loaded with at least one fluorescent dye, the dye carrier having a bottom surface, the dye carrier being detachably coupled thereto at least a portion of the outer surface of the distal end of the probe such that the entire bottom surface of the dye carrier is radially spaced from the longitudinal axis and the objective lens of the probe to permit direct transmission of light between the objective lens of the probe and the selected tissue, wherein the bottom surface of the dye carrier is configured to selectively contact the selected tissue of the subject to diffuse the at least one fluorescent dye through the bottom surface of the dye carrier and into the selected tissue of the subject,
wherein, following diffusion of the at least one fluorescent dye into the selected tissue, the image transmission means and the objective lens are configured to transmit light to the selected tissue and to receive emitted light from the selected tissue.

2. The fluorescence imaging device of claim 1 , wherein the at least one fluorescent dye is suspended in a buffer solution.

3. The fluorescence imaging device of claim 2 , wherein the at least one fluorescent dye and the buffer solution together comprise at least 95% by weight of the dye carrier.

4. The fluorescence imaging device of claim 1 , wherein the dye carrier comprises at least one antibody agent.

5. The fluorescence imaging device of claim 1 , wherein the at least one fluorescent dye is selected from a group consisting of: Alexa, Texas Red, FITC, Oregon Green, Rhodamine Green, Lucifer yellow, Fluo 3, Fluo 4, Fluorescite and di-8-Anepps.

6. The fluorescence imaging device of claim 1 , further comprising means for steering the probe such that the bottom surface of the dye carrier contacts a desired region of the tissue of the subject.

7. The fluorescence imaging device of claim 1 , wherein the probe has a longitudinal length, and wherein the central bore of the probe has a constant diameter along the longitudinal length of the probe.

8. The fluorescence imaging device of claim 1 , wherein the probe has a longitudinal length, and wherein the central bore of the probe has a variable diameter along the longitudinal length of the probe.

9. The fluorescence imaging device of claim 8 , wherein the diameter of the central bore is reduced proximate the distal tip of the probe.

10. The fluorescence imaging device of claim 9 , wherein the outer diameter of the probe remains constant along the longitudinal length of the probe.

11. The fluorescence imaging device of claim 9 , wherein the outer diameter of the probe varies along the longitudinal length of the probe.

12. The fluorescence imaging device of claim 11 , wherein the outer diameter of the probe is reduced proximate the distal tip of the probe.

13. The fluorescence imaging device of claim 1 , wherein the outer surface of the probe defines one or more protrusions proximate the distal end of the probe, and wherein the dye carrier comprises one or more channels configured to receive corresponding protrusions of the probe, the one or more protrusions of the probe configured to engage the dye carrier such that the dye carrier is detachably secured thereto the probe.

14. The fluorescence imaging device of claim 13 , wherein the one or more protrusions comprise a rim extending circumferentially around the probe along at least a portion of the outer surface of the probe.

15. The fluorescence imaging device of claim 1 , further comprising an outer casing that surrounds the dye carrier and is configured to limit the dispensing of the at least one fluorescent dye to a distal portion of the dye carrier that includes the bottom surface of the dye carrier.

16. The fluorescence imaging device of claim 1 , wherein the image transmission means of the probe comprises a fiber-optic bundle, and wherein the objective lens and the fiber-optic bundle have a common longitudinal axis parallel to the longitudinal axis of the probe.

17. The fluorescence imaging device of claim 15 , wherein the casing comprises an attachment means configured for engagement with the probe.

18. The fluorescence imaging device of claim 1 , wherein the foam of the dye carrier comprises polyurethane foam.

19. A system for fluorescence imaging of tissue, comprising:
a processor;
a light source; and
a fluorescence imaging device that is operatively coupled to the processor and comprises:
a probe defining a central bore, the probe having an outer surface, a distal end, an opposed proximal end, and a longitudinal axis extending between the distal end and the proximal end of the probe, the distal end defining a distal tip configured to contact a selected tissue of a subject, the outer surface of the probe extending away from the distal tip in a proximal direction and defining an outer diameter of the probe along a longitudinal length of the probe, the probe comprising:
an image transmission means positioned therein the central bore of the probe and placed in communication with the light source and the processor; and
an objective lens positioned therein the central bore of the probe proximate the distal tip of the probe; and

an annular dye carrier comprising an open-cell polymer foam filled at least partially with a hydrogel, the dye carrier being loaded with at least one fluorescent dye, the dye carrier having a bottom surface, the dye carrier being detachably coupled thereto at least a portion of the outer surface of the distal end of the probe such that the entire bottom surface of the dye carrier is radially spaced from the longitudinal axis and the objective lens of the probe to permit direct transmission of light between the objective lens of the probe and the selected tissue, wherein the bottom surface of the dye carrier is configured to selectively contact the selected tissue of the subject to diffuse the at least one fluorescent dye through the bottom surface of the dye carrier and into the selected tissue of the subject,

wherein, following diffusion of the at least one fluorescent dye into the selected tissue, the image transmission means and the objective lens are configured to transmit light to the selected tissue and to receive emitted light from the selected tissue.

20. The system of claim 19 , wherein the processor is configured to process received emitted light from the at least one fluorescent dye to form a fluorescence image.

21. The system of claim 20 , wherein the processor is configured to characterize the micro-structure of tissue within the fluorescence image.

22. The system of claim 21 , wherein the processor is further configured to ide

Assignees

• Univ Utah Res Found

Inventors

• Sachse Frank B
• Hitchcock Robert
• Huang Chao
• Kaza Aditya K

Classifications

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G01N2021/6463

  Optics · CPC title

• G01N21/6456

  Spatial resolved fluorescence measurements; Imaging · CPC title

• A61B5/0068

  Confocal scanning · CPC title

• A61M5/007

  for contrast media · CPC title