Optical analysis system and approach therefor

• US 9,839,361 B2
• Filed: 10/06/2015
• Issued: 12/12/2017
• Est. Priority Date: 01/24/2005
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Schnitzer, Mark Jacob, Jung, Juergen Claus
• Primary Examiner(s): Le, Long V
• Assistant Examiner(s): HOFFA, ANGELA MARIE
• Application Number:
  US14/876,620
• Publication Number:
  US 20160022148A1
• Time in Patent Office: 798 Days
• CPC Class Codes: A61B 1/00009 of image signals during a use of endoscope
• CPC Class Codes: A61B 1/00165 with light-conductive means, e.g. fibre optics A61B1/07 takes precedence
• CPC Class Codes: A61B 1/04 combined with photographic or television appliances
• CPC Class Codes: A61B 1/043 for fluorescence imaging
• CPC Class Codes: A61B 1/06 with illuminating arrangements
• CPC Class Codes: A61B 1/07 using light-conductive means, e.g. optical fibres
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 5/0042 for the brain
• 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 5/0062 Arrangements for 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 5/24 Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence

Abstract

Imaging, testing and/or analysis of subjects are facilitated with a capillary-access approach. According to an example embodiment, a capillary is implanted into a specimen and adapted to accept an optical probe to facilitate optical access into the specimen. In some applications, the capillary is implanted for use over time, with one or more different probes being inserted into the capillary at different times, while the capillary is implanted. Certain applications involve capillary implantation over weeks, months or longer. Other applications are directed to the passage of fluid to and/or from a sample via the capillary. Still other applications are directed to the passage of electrical information between the sample and an external arrangement, via an implanted capillary.

Claims

1. A method of repeatedly generating in vivo, cellular resolution images from a target region in a subject in iterative imaging sessions, comprising:

providing an imaging system, the imaging system including (a) a light conduit, (b) a housing (1) affixed to the subject and (2) configured and arranged to repeatedly accept, and provide stable optical access to the target region for the light conduit, and (c) a detector configured to (1) generate a signal from light collected by the light conduit, and (2) pass said signal to an image processor used to generate structural cellular resolution images;

enabling the optical access, with the aid of the imaging system, into the target region for a time period lasting from a first iterative imaging session to a subsequent iterative imaging session; and

conducting iterative cellular resolution imaging sessions with the aid of the imaging system, each imaging session including

(i) directing light to the target region with aid of the light conduit, thereby inducing response light from the target region, and

(ii) generating structural cellular resolution in vivo images from the response light with the aid of the light conduit and the detector,

wherein the step of conducting iterative cellular resolution imaging sessions comprises (1) removing the light conduit from the housing after the first iterative imaging session, (2) re-inserting the light conduit into the housing to perform the subsequent imaging session, and (3) keeping the housing affixed to the subject between the first iterative imaging session and the subsequent imaging session.

2. The method of claim 1, wherein the light conduit comprises one or more of a single conduit, two or more light conduits, a fiber optic conduit, a microendoscope probe, or a bundle of optical fibers.

3. The method of claim 1, further comprising allowing the subject to engage in freely ranging behavior after removing the light conduit from the housing after the first iterative session and before the subsequent imaging session.

4. The method of claim 3, wherein the subject engages in the free ranging behavior during a time period between the first iterative imaging session and the subsequent imaging session, during which light conduit is removed from the housing.

5. The method of claim 1, wherein the step of conducting iterative cellular resolution imaging sessions further comprises focusing light to a selected depth to access the target region within a tissue sample.

6. The method of claim 1, wherein the imaging system comprises one or more optical elements configured to pass light between the target region and the detector.

7. The method of claim 6, wherein the one or more optical elements comprise a beamsplitter.

8. The method of claim 1, further comprising resolving, during the cellular imaging session, structures with a dimension of dendritic spines, stereocilia, or mitochondria.

9. The method of claim 1, wherein the target region comprises a subcutaneous tissue sample.

10. The method of claim 1, wherein a time period between the first iterative imaging session and the subsequent imaging session during which the light conduit is removed from the housing is 24 hours or more.

11. The method of claim 1, wherein the subject is a live rodent.

12. The method of claim 11, wherein the target region is a brain of the live rodent.

13. The method of claim 1, further comprising monitoring electrophysiological responses of the target region in vivo.

14. The method of claim 1, wherein the image processor is a computer configured to reconstruct and display the cellular resolution images.

15. The method of claim 1, wherein the light collected by the light conduit is a response light from the target region.

16. The method of claim 15, wherein the light from the light sources passes through a beamsplitter before being collected by the light conduit.