With the recent introduction of full-face transplantation, it is more important than ever to ensure survival of a transplanted graft. However, flap viability is currently assessed using only subjective clinical criteria or biopsy. Similarly, the field of head and neck reconstructive surgery is struggling to reduce a total flap loss rate as high as 14%. In addition to overt failures, complication rates range from 21% to 43%, leaving patients with a prolonged stay in the ICU, decreased quality of life, and additional healthcare costs. Every year, over 87,000 patients in the US undergo some type of head and neck reconstruction, and new technology that permits objective, noninvasive assessment of flap viability intraoperatively and postoperatively is desperately needed. The hypothesis guiding this study is that near-infrared (NIR) light interacts deeply with living tissue constituents, namely oxyhemoglobin, deoxyhemoglobin, lipids, and water, providing quantitative measurement of physiological parameters, such as oxygenation, metabolism, and hydration. Such information can be used to monitor facial flap transplant viability intraoperatively and postoperatively, in a noninvasive manner and in real time. State-of-the-art NIR endogenous imaging consists of multispectral spatial frequency domain imaging (SFDI) that can accurately provide quantitative images of tissue constituents over large fields of view. The technology we propose to develop is analogous to pulse oximetry. But, rather than sample a single point of the body with NIR light, it provides a complete image of tissue oxygenation and perfusion over the skin surface, and can even separate the contributions of oxyhemoglobin and deoxyhemoglobin to oxygen saturation. To test whether NIR optical imaging has the potential to monitor facial flap viability, we have assembled a multi-institutional team of experts from image-guided surgery, clinical translation, SFDI, and reconstructive surgery. Dr. Bruce Tromberg at UC Irvine is an international leader in biomedical optics whose laboratory first developed the SFDI technique. Dr. Bernard Lee is an active, board-certified plastic and reconstructive surgeon at BIDMC. Our own team at BIDMC has a long and productive track record in intraoperative NIR imaging, with a particular focus on plastic and reconstructive surgery. By leveraging this strong collaboration of experts, our study aims to solve a longstanding problem in facial reconstructive surgery, namely the noninvasive monitoring of tissue transplants intraoperatively and postoperatively using NIR light. Specific aims include optimization of the SFDI technology to permit real-time imaging (< 1 frame per second) of facial transplants, including correction for the complex geometry of the face, the development of a quantitative optical metric of the transplant status, and validation of the optimized method on large animals approaching the size of humans. Completion of these aims has the potential to revolutionize head and neck surgery, especially facial transplants, by providing critical feedback to surgeons, thus permitting them to identify tissue compromise and prevent complications before they occur.