CAREER: Functional Optical Coherence Tomography for Neural Imaging

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0347747BoppartOptical coherence tomography (OCT) is an emerging high-resolution biomedical imaging modality with potential applications in a wide range of medical and biological specialties. Studies to date have used OCT primarily to non-invasively image morphology. Doppler and polarization-sensitive OCT have been used to assess functional properties of tissue, but most commonly in blood flow and tissue injury, respectively. The capabilities of OCT, however, extend far beyond microanatomical imaging. Just as functional magnetic resonance imaging has had a significant impact on our understanding of cognitive processes in the brain, functional OCT (fOCT) techniques have the potential for investigating neural activity and communication patterns at the cellular and molecular level. For this CAREER Development Award, fOCT methods will be developed to visualize not only anatomical microstructure but also physiological function in neurons and in neural tissue. Novel optical methods will be developed to non-invasively characterize electrical and molecular function. To investigate and demonstrate the capabilities of these imaging methods, fOCT will be used in three representative cell culture and small animal models. Functional OCT detecting scattering and birefringence changes will be used to non-invasively detect electrical neural activity in cultured neuron populations without the addition of exogenous fluorophores and without the need for multiple electrode arrays and electronics. In the abdominal ganglion of Pleurobranchaea (sea slug), neural pathways will be mapped out using real-time fOCT imaging and compared to known networks. Differences in functional molecules (oxygen, acetylcholine, Fragile X mental retardation protein [FMRP]) in the brains of normal and Fragile X mouse models will be characterized using spectroscopic and nonlinear OCT methods. This project will develop novel fOCT methods that comprise an integrated imaging system. This system will establish fOCT and these methods as powerful neural imaging tools for a wide-range of investigations.The research will be integrated with educational plans to engage K-12, undergraduate and graduate students and post-doctoral fellows of highly diverse backgrounds. Two exhibits will be designed and constructed for the local Science Museum targeted toward the K-12 audience, one on "Biophotonics" and the other on "Nature's Optics." Research results will be integrated into existing undergraduate courses in Optical Imaging and Biomedical Instrumentation and efforts will intensify to develop an optics track and initiate a new course in Biophotonics. An international graduate student exchange with colleagues' laboratory will be arranged and a graduate-level seminar series on Biophotonics will be initiated.