Direct visualization of tissue physiology and anatomy provides important information to the physician for the diagnosis and management of disease. High spatial resolution noninvasive techniques for imaging in vivo tissue structure and blood flow dynamics are currently not available as a diagnostic tool in clinical medicine. Such techniques could have a significant impact for biomedical research and patient treatment. The objective of the proposed research is to develop a high speed noninvasive optical technique, optical coherence tomography (OCT) and optical Doppler tomography (ODT), for imaging in vivo tissue structure and blood flow with high spatial resolution (2-10mum) in biological tissues. Preliminary results obtained in our laboratory have demonstrated the potential of this technology for a number of clinical applications where imaging tissue structure and monitoring hemodynamics are important. However, there are four limitations in our current OCT/ODT system: speed, resolution, penetration depth and speckle noise. The proposed research is directed toward the development of a high speed, high resolution, phase resolved OCT/ODT system for imaging tissue structure and microcirculation that overcomes these limitations. The specific aims of this proposal are to: (1) design and develop a high speed high resolution phase resolved OCT/ODT system for tomographic imaging of in vivo tissue structure and blood flow dynamics in highly scattering biological tissues; (2) develop signal processing and image reconstruction software and hardware for phase resolved OCT/ODT; (3) image blood flow in vitro using reconstituted canine blood and in vivo using the chick chorioallantoic membrane (CAM) model to verify and optimize OCT/ODT system operation and spatial resolution; and (4) demonstrate in animal models and clinical studies how OCT/ODT can assist in diagnosis and treatment of skin tumors and port wine stain birthmarks where imaging tissue structure and monitoring blood flow are important.