Nerve trauma is a major cause of morbidity associated with surgery and can lead to loss of sensation, chronic postsurgical pain, and erectile dysfunction. Although human nerve anatomy is known, precisely locating tissue- embedded nerves is challenging during surgery due to individual anatomical variation, intricacy, and size. De- spite the use of nerve sparing techniques, the risk of iatrogenic nerve damage remains high in a wide array of prominent open and minimally invasive surgeries, ranging from radical prostatectomy (prostate cancer), coro- nary artery bypass graft (cardiovascular disease), lymph node dissection (breast cancer), and spine surgery. The team proposes to improve intra operative detection of nerves through two complimentary technologies: (1) near infrared fluorescent contrast agents targeting nerves, and (2) dedicated compact and minimally invasive surgical instruments to simultaneously image nerve fluorescence and anatomy in real-time. The ability of these molecular imaging agents and surgical instruments to visualize nerves will be validated in preclinical models. The long-term goal of this study is to provide tools for surgeons to minimize iatrogenic nerve damage, expedite surgical procedures, enhance surgical efficiency, and improve patient outcomes. PUBLIC HEALTH RELEVANCE: Nerve damage during surgery can have a significant deleterious effect on patient quality of life. Unintentional damage to nerves can lead to chronic pain, loss of sensation, and erectile dysfunction. A method to better visualize nerves during surgery would improve patient outcome by reducing the risk of nerve damage.