PROJECT SUMMARY We propose to develop a novel non-contact, label-free multimodality imager that provides real-time intraoperative identification of nerves within the surgical field-of-view to facilitate the prevention of unintended nerve damage (termed iatrogenic nerve injury) during surgical procedures, as they are a major source of postsurgical complications, e.g., chronic pain. In the United States chronic pain management is a major putative contributing factor in the current opioid-related drug overdose epidemic. Annually, over 45 million surgical procedures are performed in the United States and an estimated 10% to 50% of them result in patient chronic postoperative pain outcomes. Though not all the at least 4.5 million are definitively ascribable to iatrogenic nerve injury, it nonetheless represents a significant recurring annual healthcare problem. Relatedly, analysis of large-scale nerve lesion treatment studies reveals that 25%, 60% and 94% respectively of sciatic, femoral and accessory nerve lesions addressed are caused by iatrogenic nerve injury. Additionally, iatrogenic nerve injury features prominently in post-surgical quality of life issues that range from loss of sensation and motor function to the aforementioned chronic pain, and morbidity. Reportedly, 2-3 years post radical prostatectomy ~60% of men are still impotent as a result of damaged cavernous nerves. Likewise, 20% - 60% of mastectomy breast cancer treatment survivors suffer chronic post-surgical pain that significantly reduces their quality of life, and injury to the intercostobrachial nerve is the primary cause. Even in surgeries with minimal neural damage risk like acoustic neuroma removal (<1%), spinal scoliosis surgery (<0.6%), and thyroidectomy (<2-3.8%) the consequences of nerve damage can be severe: leading to deafness, paraplegia, and even death respectively. The associated financial implications of iatrogenic nerve damage are significant. There are direct financial costs to the individual due to loss of employment and/or income, and to the healthcare industry as nerve damage is a common source of litigation with compensation being awarded in 82% of cases of spinal accessory nerve injury, for an example. The exposure of healthcare personnel and providers to medicolegal liability is extensive as Iatrogenic nerve injuries are commonly reported on the laryngeal nerve during thyroid operations, trigeminal nerve and inferior alveolar nerve during facial and oral surgeries, intercostal nerves during thoracic surgeries, and on the spinal accessory nerves, common peroneal nerve, superficial radial nerve, and genitofemoral nerve branches during various other surgeries. Consequently, as of 2022, medicolegal litigation risk was a primary driver for a $1.5 billion global market for intraoperative nerve monitoring projected to grow at 5.1% annually through 2030. Our proposed solution targets filling both the deficiencies of currently available options and the growing demand by introducing an effective, commercially viable product.

PROJECT NARRATIVE Unintended nerve damage during surgical procedures is a significant and costly public healthcare delivery problem and current methods for injury prevention via intraoperative nerve monitoring leave substantial room for improvement. The ramifications of increased healthcare costs due to associated medical-liability issues and the significant reductions in quality-of-life issues, including the burgeoning chronic pain management related opioid- related drug overdose epidemic, make addressing this very impactful to society. The proposed development will yield an effective, commercially viable, non-contact multimodality imager that provides realtime intraoperative identification of nerves within the surgical field-of-view to facilitate the prevention of unintended nerve damage during surgical procedures.