The overall goal of this project is to improve the care of diabetic patients undergoing surgery for treatment of osteomyelitis. This improvement will be attained by providing immediate intraoperative imaging feedback to podiatrists and surgeons as to whether surgical margins are clear of involvement, and whether remaining tissues are healthy. Often, patients reside in hospital beds while pathological assessment of tissue specimens is pending, adding to overall care costs and exposing patients to potential nosocomial infection. A rapid and reliable method of assessing surgical margins intraoperatively could potentially reduce hospital stays. Providing additional confidence might allow surgeons and podiatrists to be more conservative in their resections, thereby improving patients'quality of life. The commercial market for diabetic osteomyelitis care has been estimated at $10 billion annually, with a similar amount for non- bone wound care. The project takes advantage of recent innovations in miniaturized fluorescence microscopes, and applies lessons learned in oncology imaging, towards the goal of rapid identification of surgical margins for osteomyelitis patients. Follow-on applications for the technology to be developed in this project include decubitus ulcer debridement, and other wound care challenges. Unlike prior imaging approaches that employed exogenous contrast materials (e.g., tetracycline, labeled radiotracers) we propose to use endogenous optically-active markers (e.g., mitochondrial NADH) to rapidly assess tissue viability in this important clinical application. The project is distinguished by a cross-cutting academic-industrial collaboration including experts in medical imaging, wound care, and sensor engineering and physics. Since the original application, and in response to the suggestions of the reviewers, our group has conducted preliminary experiments validating the basic physiological assumptions that the project is based on. The results of these pilot studies are included in the revised application. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to improve the care of diabetes patients undergoing surgery for treatment of osteomyelitis. This improvement will be attained by providing immediate intraoperative imaging feedback to podiatrists and surgeons as to whether surgical margins are clear of involvement, and whether remaining tissues are healthy. Often, patients reside in hospital beds while pathological assessment of tissue specimens is pending, adding to overall care costs and exposing patients to potential hospital-acquired infections. A rapid and reliable intraoperative method of assessing surgical margins could potentially reduce hospital stays. Providing additional confidence might allow surgeons and podiatrists to be more conservative in their resections, thereby improving patients'quality of life.