[unreadable] This K99/R00 proposal on the development of optical methods for imaging transient structural changes associated with neural activity integrates rigorous physics, biomedical, and neuroscience research, close career mentoring, and tailored coursework to establish Dr. B. Hyle Park as an independent investigator. Having completed his graduate research in physics, Dr. Park is now continuing his research at the Wellman Center for Photomedicine as a research fellow and is making the transition to research independence. He has focused on biomedical imaging, particularly in the development and clinical application of polarization- sensitive optical coherence tomography. Dr. Park now seeks to complement this grounding in biomedical optics with mentored research in the application of these optical techniques to neuroscience. His research proposal addresses the need for non-contact detection of neural structure and activity. Current techniques for detection of action potential propagation involve direct contact with electrodes or introduction of chemical markers, such as Ca++ dyes. In this K99/R00, he focuses on optical detection of transient structural changes that accompany spike propagation in neurons using phase-sensitive interferometry. Successful completion of the proposed research will enable optical detection of the structure and activity of nerves and neuronal ensembles in vitro, and lay the groundwork for in vivo application as well as providing the preliminary results necessary for a successful R01 application. This work not only has potential application as a complement to electrophysiology, but would be of use in clinically important regions, such as the retina, that are largely inaccessible with current techniques. Co-mentor Dr. Johannes F. de Boer has an established track record in the development of optical imaging methods and has successfully translated emerging research to ophthalmological and clinical use. Co-mentor Dr. Christopher L. Passaglia has experienced similar success in the study of how visual information is represented in the eye's input to the brain and how that changes as diseases, like glaucoma, inflict damage upon the retina. In addition to their supervision, Dr. Park will have access to coursework in neuroscience, and the ethical conduct of research at Harvard Medical School. The opportunities provided by this career award will allow Dr. Park to combine expertise in physics and biomedical optics with neuroscience, substantially adding to his capabilities as an independent researcher. [unreadable] [unreadable] [unreadable] [unreadable]