Devices and systems for fluorescence imaging of tissue

• US 10,154,785 B2
• Filed: 01/18/2013
• Issued: 12/18/2018
• Est. Priority Date: 01/18/2012
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Sachse, Frank B., Hitchcock, Robert, Huang, Chao, Kaza, Aditya K.
• Primary Examiner(s): Park, Patricia
• Assistant Examiner(s): Sunwoo, Nate S
• Application Number:
  US14/373,014
• Publication Number:
  US 20150119708A1
• Time in Patent Office: 2,160 Days
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2576/023 for the heart
• CPC Class Codes: A61B 5/0044 for the heart
• CPC Class Codes: A61B 5/0068 Confocal scanning
• 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: A61B 5/02028 Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• CPC Class Codes: A61B 5/4887 Locating particular structures in or on the body
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0073 semi-solid, gel, hydrogel, ointment
• CPC Class Codes: A61M 5/007 for contrast media
• CPC Class Codes: G01N 2021/6423 Spectral mapping, video display
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging

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.

Claims

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 identify conductive tissue within the selected tissue.

23. The system of claim 19, further comprising packaging for the dye carrier, wherein the packaging defines:

a chamber configured to receive the dye carrier for storage; and

a removal feature positioned vertically above the chamber, wherein after lateral insertion of the dye carrier into the chamber using the probe, the removal feature is configured to engage the dye carrier and promote detachment of the dye carrier from the probe as the probe is vertically withdrawn from the packaging.

24. A method of fluorescence imaging of selected tissue of a subject, comprising:

using a fluorescence imaging 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, 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;

a fiber optic bundle positioned therein the central bore of the probe and positioned in 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 of the probe and the objective lens of the probe to permit direct transmission of light between the objective lens of the probe and the selected tissue;

selectively contacting the selected tissue of the subject with the bottom surface of the dye carrier to diffuse the at least one fluorescent dye through the bottom surface of the dye carrier and into the selected tissue of the subject;

following diffusion of the at least one fluorescent dye into the selected tissue, using the fiber optic bundle and the objective lens to transmit light to the selected tissue and to receive emitted light from the selected tissue; and

using a processor coupled to the fiber optic bundle, processing received emitted light from the selected tissue to form a fluorescence image.

25. The method of claim 24, further comprising using the processor to characterize the micro-structure of tissue within the fluorescence image, wherein the characterization of the micro-structure of the tissue comprises identifying conductive tissue within the tissue.