The ideal neuroimaging technique would provide exquisite structural detail and also provide functional information, with high spatial and temporal resolution. Optical coherence tomography (OCT) is an optical imaging technique in which light from a low coherent source illuminates tissue and reflectivity of internal microstructures at different depths is measured by an interferometer. OCT is capable of micrometer-spatial and millisecond-temporal resolutions, without the use of exogenous contrast agents (hence label-free). The objective in this application is to develop and validate OCT for mammalian brain functional imaging; correlate OCT images with cellular electrophysiology assessed by multielectrode array (MEA); and provide proof-of- principle for OCT-based detection of neural activity.
Two specific aims will be pursued: (1) Validate detection of multi-unit activity (MUA) by optical coherence tomography (OCT) in hippocampal slices. Our previous data demonstrate that OCT can detect synchronous cellular firing associated with both generalized and focal seizure activity. However, the sensitivity of OCT to physiological events such as multiunit activity (MUA) has not yet been determined. In this Aim, MUA induced by 4-aminopyridine (4-AP) and high K+ will be correlated to OCT. (2) Validate detection of local stimulation-induced synaptic activation by OCT. To allow more precise control of local stimulation site and intensity, in this Aim we will use local stimulation of a defined synaptic pathway in the hippocampal slice combined with OCT-based detection. Stimulation of the Schaffer collateral pathway from CA3 to CA1 will be performed by (1) electrical stimulation and (2) optogenetic stimulation to trigger MUA in CA1 that will be then detected by MEA and correlated to the changes in the optical signal by OCT. Our approach is innovative in adapting OCT for brain functional imaging. The proposed research is significant because it will lead to the validation of OCT as a neuroimaging tool for research in neuroscience.

Public Health Relevance

The proposed research is relevant to public health because brain imaging with optical coherence tomography will help to develop tools for label-free optical detection of neural activity. An entirely novel system for OCT brain imaging and detection of brain activity will be developed, integrating principles from a diversity of technical and biomedical fields and with the support of a multidisciplinary team. Thus, the proposed research is relevant to the part of NIH's mission that pertains to providing new basic understandings, novel products, and innovative technologies that improve basic knowledge, human health, and quality of life.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY026441-02
Application #
9145711
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Wujek, Jerome R
Project Start
2015-09-30
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
2
Fiscal Year
2016
Total Cost
$232,500
Indirect Cost
$82,500
Name
University of California Riverside
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Tong, Minh Q; Hasan, Md Monirul; Lee, Sang Soo et al. (2017) OCT intensity and phase fluctuations correlated with activity-dependent neuronal calcium dynamics in theDrosophilaCNS [Invited]. Biomed Opt Express 8:726-735