Optogenetic magnetic resonance imaging

Patent metadata

Field	Value
Publication number	US-9271674-B2
Application number	US-201414298413-A
Country	US
Kind code	B2
Filing date	Jun 6, 2014
Priority date	Nov 22, 2010
Publication date	Mar 1, 2016
Grant date	Mar 1, 2016

Abstract

Disclosed herein are systems and methods involving the use of magnetic resonance imaging and optogenetic neural stimulation. Aspects of the disclosure include modifying a target neural cell population in a first region of a brain to express light-responsive molecules. Using a light pulse, the light-responsive molecules in the target neural cell population are stimulated. Multiple regions of the brain are scanned via magnetic resonance imaging. The scans allow for observation of a neural reaction in response to the stimulation in at least one of the multiple regions of the brain.

First claim

What is claimed is:

1. A method comprising:
modifying a target neural cell population in a first region of a brain to express a light-responsive opsin polypeptide;
stimulating, using a light pulse, the light-responsive opsin polypeptide in the target neural cell population;
scanning multiple regions of the brain via functional magnetic resonance imaging to observe a neural reaction in response to the stimulation in at least one of the multiple regions of the brain and, in response, determine whether neural projections in a second region of the brain are connected to at least some of the modified target cell population in the first region of the brain.

2. The method of claim 1 , further including stimulating the light-responsive polypeptide at a first light pulse rate and a second light pulse rate.

3. The method of claim 1 , wherein the first region of the brain is in the motor cortex.

4. The method of claim 1 , further including calibrating the stimulation of the light- responsive opsin polypeptide to provide a response in the second region within a desired range of responses.

5. The method of claim 1 , wherein the observed neural reactions are used to determine a treatment plan for a disease effecting at least one of the first or second regions of the brain.

6. The method of claim 1 , further comprising introducing a drug into the brain, and repeating the steps of stimulating the light-responsive opsin polypeptide, and scanning multiple regions of the brain; and determining the effectiveness of the drug based on a comparison of the observed neural reactions in the scan before the introduction of the drug and the observed neural reactions in the scan after the introduction of the drug.

7. The method of claim 1 , further including:
modifying a second target neural population in the first region of the brain to express a second type of light-responsive opsin polypeptide;
stimulating the second type of light-responsive opsin polypeptide in the second target neural population;
scanning multiple regions of the brain via functional magnetic resonance imaging to observe a neural reaction in response to the stimulation of the second neural population in at least one of the multiple regions of the brain and determine therefrom whether neural paths in the second region of the brain are neurally connected to at least some of the modified second target neural populations in the first region of the brain.

8. The method of claim 2 , wherein the results of the observation of first stimulation and the second stimulation are combined, and providing a functional map of the brain including at least the results of the first observation and the second observation.

9. A method comprising:
modifying a target neural cell population to express a light-responsive opsin polypeptide in a first region of a brain, wherein the light-responsive opsin polypeptide modulates an activity of the target cell population in response to light;
stimulating the light-responsive opsin polypeptide in the target neural cell population using light pulses;
scanning at least the first region of the brain via functional magnetic resonance imaging (fMRI);
stimulating the target neural cell population using an electric pulse;
performing fMRI scans and observing a blood oxygenation level-dependent (BOLD) signal response to excitation of the target cell population using electronic stimulation; and
based at least in part on the BOLD signal responses in the target cell population due to light stimulation and electronic stimulation, assessing the BOLD fMRI scan.

10. The method of claim 1 , wherein the light-responsive opsin polypeptide is a channelrhodopsin.

11. The method of claim 10 , wherein the light-responsive opsin polypeptide is a ChR2 or a VChR1 channelrhodopsin.

12. The method of claim 1 , wherein the light-responsive opsin polypeptide is an NpHR ion pump.

13. The method of claim 1 , wherein the light-responsive opsin polypeptide is encoded by a nucleotide sequence that is operably linked to a neuron-specific promoter.

14. The method of claim 13 , wherein the neuron-specific promoter is a CaMKIIα promoter.

15. The method of claim 1 , wherein the first region of the brain is in the thalamus.

16. The method of claim 1 , wherein the light is delivered by an optical fiber.

17. The method of claim 1 , wherein target neural cell population is modified using a recombinant expression vector encoding the light-responsive opsin polypeptide.

18. The method of claim 17 , wherein the recombinant expression vector is delivered to the target neural cell population via a cannula.

Assignees

• Univ Leland Stanford Junior

Inventors

• Deisseroth Karl
• Lee Jin Hyung

Classifications

• G16H30/40

  for processing medical images, e.g. editing · CPC title

• A61N5/0622

  Optical stimulation for exciting neural tissue · CPC title

• A61B5/055

  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging · CPC title

• G01R33/4806 Primary

  Functional imaging of brain activation · CPC title

• G16H30/20

  for handling medical images, e.g. DICOM, HL7 or PACS · CPC title