DYE APPLICATION FOR CONFOCAL IMAGING OF CELLULAR MICROSTRUCTURE

• US 20110301438A1
• Filed: 08/04/2009
• Published: 12/08/2011
• Est. Priority Date: 08/04/2008
• Status: Active Grant

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Hitchcock, Robert, Sachse, Frank B., Bridge, John H.
• Granted Patent: US 8,620,409 B2
• Time in Patent Office: Days
• US Class Current: 600/301
• CPC Class Codes: A61B 1/0008 characterised by distal tip features
• CPC Class Codes: A61B 1/043 for fluorescence imaging
• 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 5/6852 Catheters
• CPC Class Codes: A61B 5/7285 for synchronising or triggering a physiological measurement or image acquisition with a physiological event or waveform, e.g. an ECG signal A61B6/5205, A61B6/541, A61B8/5207, A61B8/543 take precedence
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: G02B 21/0028 specially adapted for specific applications, e.g. for endoscopes, ophthalmoscopes, attachments to conventional microscopes
• CPC Class Codes: G02B 21/0032 Optical details of illumination, e.g. light-sources, pinholes, beam splitters, slits, fibers G02B21/0036 - G02B21/008; means for illumination of specimens in general G02B21/06
• CPC Class Codes: G02B 21/0076 arrangements using fluorescence or luminescence

Abstract

A system and method for confocal imaging of tissue in vivo and in situ, e.g., for minimally invasive diagnosis of patients. A catheter is provided that has a dye carrier coupled to the distal end of 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 confocal images permit the acquisition of diagnostic information on the progression of diseases at cellular/tissue level in patients. Furthermore, a system for ECG-triggered image acquisition is provided.

Claims

1. A method for imaging of tissue, comprising:

providing a fiber optic bundle having a distal end;

operatively coupling a dye carrier to the distal end of the fiber optic bundle, the dye carrier comprising at least one fluorescent dye;

positioning a portion of the dye carrier in contact against a tissue region of interest to selectively introduce at least a portion of the at least one fluorescent dye into the tissue region of interest;

generating light at a desired wavelength;

transmitting the light into the fiber optic bundle and through the dye carrier onto the tissue region of interest to excite the fluorescent dye therein the tissue.

2. The method of claim 1, further comprising receiving light emitted from the excited fluorescent dye therein the fiber optic bundle and communicating the emitted light to a confocal microscopic imaging system.

3. The method of claim 2, further comprising processing the received emitted light to form the confocal image.

4. The method of claim 1, further comprising monitoring an ECG signal taken from the subject, wherein a reference point of the ECG signal taken from the subject triggers the image acquisition.

5. The method of claim 4, wherein the step of light transmission is repeated at each sequential reference point on the ECG signal

6. The method of claim 5, further comprising receiving light emitted from the excited fluorescent dye as a result of each light transmission therein the fiber optic bundle and communicating the emitted light to a confocal microscopic imaging system.

7. The method of claim 6, further comprising processing the received emitted light to form the confocal image.

8. The method of claim 1, wherein the dye carrier comprises a light transparent matrix and the at least one fluorescent dye.

9. The method of claim 2, wherein the at least one fluorescent dye is suspended in a buffer solution.

10. The method of claim 9, wherein the at least one fluorescent dye and the buffer solution comprises at least 95% of the dye carrier.

11. The method of claim 8, wherein the at least one fluorescent dye is at a predetermined concentration.

12. The method of claim 8, wherein the dye carrier comprises at least one antibody agent.

13. The method 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, and di-8-Anepps.

14. The method of claim 1, wherein the at least one fluorescent dye has a molecular weight of 40 KDa or less.

15. The method of claim 14, wherein the at least one fluorescent dye has a molecular weight of 20 KDa or less.

16. The method of claim 1, wherein the at least one fluorescent dye has a molecular weight of between about 3 KDa and about 10 KDa.

17. The method of claim 8, wherein the light transparent matrix comprises a hydro-gel.

18. The method of claim 17, wherein the light transparent matrix extends from the distal end of the fiber optic bundle for less than 100 μ

m.

19. The method of claim 17, wherein the light transparent matrix extends from the distal end of the fiber optic bundle for less than 200 μ

m.

20. The method of claim 1, wherein the tissue of interest is cardiac tissue.

21. A catheter for developing a confocal image of a tissue of a subject in a confocal microscopic imaging system comprising a processor and a source of light energy that is configured for selective generation of light energy at a desired wavelength, comprising:

a fiber-optic bundle having a distal end and an opposed proximal end, the proximal end in operable communication with the confocal microscopic imaging system, wherein the fiber-optic bundle is in communication with the source of light energy; and

a means for positioning at least one fluorescent dye to the distal end of the fiber-optic bundle.

22. The catheter of claim 21, further comprising a means for positioning a portion of the dye carrier in contact against a tissue region of interest to selectively introduce the at least one fluorescent dye into the tissue region of interest.

23. The catheter of claim 22, wherein the processor is configured for processing received emitted light from the at least one fluorescent dye to form the confocal image.

24. The catheter of claim 23, wherein the processor is configured to trigger confocal imaging using the subject'"'"'s ECG signal.

25. The catheter of claim 22, wherein the means for positioning at least one fluorescent dye to the distal end of the fiber-optic bundle comprises a dye carrier coupled to the distal end of the fiber-optic bundle, wherein the at least one fluorescent dye is loaded therein the dye carrier, and wherein the dye carrier comprises a light transmissive matrix.

26. The catheter of claim 25, wherein the at least one fluorescent dye is suspended in a buffer solution.

27. The catheter of claim 26, wherein the at least one fluorescent dye and the buffer solution comprises at least 95% of the dye carrier.

28. The catheter of claim 25, wherein the at least one fluorescent dye is at a predetermined concentration.

29. The catheter of claim 25, wherein the dye carrier comprises at least one antibody agent.

30. The catheter of claim 21, 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, and di-8-Anepps.

31. The catheter of claim 25, further comprising a catheter sheath that is configured to selectively and at least partially enclose a distal end portion of the fiber optic bundle.

32. The catheter of claim 31, wherein the catheter sheath that is configured to selectively and at least partially enclose at least a portion of the dye carrier.

33. The catheter of claim 32, wherein the means for positioning a portion of the dye carrier in contact against a portion of a desired tissue of interest comprises a means for steering the catheter sheath within the subject to position the dye carrier against the desired tissue of interest.

34. The catheter of claim 21, wherein the source of light energy is a laser.