Project Abstract Oral and Head and neck squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. The primary management of OSCC relies on complete surgical resection of the tumor. However, the establishment of margin-free resection is often difficult given the devastating side effects of aggressive surgery and the anatomic proximity to vital structures such as the carotid artery and the spinal cord. Positive margin status is associated with significantly decreased survival. Currently, it is the surgeon's fingers that determine where the tumor cuts are made, by palpating the edges of the tumor. Accuracy varies widely based on the experience of the surgeon and the location and type of tumor. Efficacy is further confounded by the risk of damage to adjacent vital structures, which limit resection margins. The goal of this proposal is to evaluate a novel, non-invasive, imaging system based on Dynamic Optical Contrast Imaging (DOCI) that has been developed to differentiate between cancerous and normal tissue intraoperatively using OSCC as the model. The imaging system is based on a novel realization of temporally dependent measurements of tissue autofluorescence that allow the acquisition of specific tissue properties over a large field of view. This system is optimized such that it can be used by surgeons at the time of cancer resection surgery to gather quantitative information on margins of malignancies and has been extensively validated in ex vivo OSCC samples. Companion histology has verified the sensitivity and specificity of the technique. In the proposed work we will reconfigure the imaging system for a large field of view (FOV), then pursue an intraoperative trial where tumors will be imaged prior to resection and wounds beds will be mapped to detect potential residual dysplastic tissue. Companion visible imagery and histology will be analyzed at all stages of the work ensuring statistical diagnostic power of the technique. We hypothesize that the accuracy and efficiency of tumor resection, margin determination and frozen sections will improve significantly when aided by our optical imaging technology. This intraoperative instrument would be the first of its kind, giving us the potential to significantly improve the sensitivity and accuracy of determining true OSCC margins thus enabling the surgeon to save healthy tissue and improve patient outcomes.