Two photon fluorescence microscopy for dermatologic surgery and biopsy

Medicare reimburses over 5 million biopsies resulting in 1.5 million surgical procedures annually for nonmelanoma skin cancer (NMSC). Despite its burden on the health care system, treatment remains time- consuming and unevenly available due to inefficient histologic methods used for diagnosis and to guide therapy. As an alternative, two photon fluorescence microscopy (TPFM) combined with rapid molecular labeling can evaluate histology dramatically faster than conventional methods. We have developed high speed TPFM imaging for dermatologic surgery, protocols for rapid molecular labeling of human tissue, and conducted preliminary studies showing that TPFM can evaluate skin cancer with similar accuracy to conventional histology. Our approach addresses the limitations of current methods, which begin with diagnosis, where the delay for histology means that patients must return for a second clinic visit if biopsies are positive. Inefficiencies are compounded during therapy, where in standard excision the delay for processing means that histology is evaluated postoperatively, and a second surgery may be required to complete therapy. Alternatively, in Mohs surgery, intraoperative frozen sections may be used, resulting in a substantial increase in procedure time and reduced clinic capacity. As a result, costs are increased and access to care is subject to regional variations, with patients in rural areas more likely to receive substandard care that puts them at risk for disfigurement or tumor recurrence. The goal of this research program is to advance two photon imaging technology for surgical applications, and then conduct clinical trials testing the use of TPFM in both diagnostic biopsy procedures and in surgical treatment of NMSC. The aims for this proposal are: Aim 1 will develop improved TPFM that incorporates recent advances in detector and laser technology to reduce cost, shrink size, and enhance contrast, providing an efficient new tool for diagnosing and treating NMSC. Concurrently, studies will examine the accuracy of TPFM for a less common type of skin cancer. Aim 2 will study patients undergoing dermatologic biopsy, testing the hypothesis that patients can be immediately diagnosed using TPFM, enabling same visit treatment for common skin cancers. Finally, Aim 3 proposes interventional surgical trials. Aim 3, Task 1 will integrate TPFM into Mohs surgery, testing the hypothesis that faster histological imaging can accelerate treatment. Aim 3, Task 2 will introduce TPFM for margin evaluation into standard (non-Mohs) excision of skin cancer, testing the hypothesis that TPFM can be used in a scenario for which no intraoperative imaging is currently practical. Collectively, these aims will test more efficient methods of diagnosing and excising skin cancer, accelerating treatment, reducing costs and morbidity while expanding access to care. Successful completion of this project would demonstrate powerful new tools for general surgical pathology and validate them for use in dermatologic surgery.