UCLA

There exists a pressing medical need for non-invasive optical tools to help surgeons intraoperatively identify tissue and determine precise tumor margins. The primary curative treatment for Head and Neck Cancer often includes complete surgical resection of the tumor, which may lead to severe loss of function, disfigurement, and poor quality of life for these patients. The goal of this dissertation is to form the foundation for successful clinical translation of Dynamic Optical Contrast Imaging (DOCI) as a label-free technique that can produce contrast from relative measurement of time-resolved tissue autofluorescence. The tool generates contrast through relative measurements of autofluorescence decay (lifetime) from tissue and thus does not require dye or injection of contrast agents. Furthermore, as opposed to intensity based approaches, these measurements depend on the intrinsic properties of tissue and provide a robust signal insensitive to inhomogeneous illumination and irregular tissue contours.

Results include the first clinical use of DOCI to produce relative lifetime tissue maps at an unprecedented six-by-six cm field of view revealing unique spectral features for individual states of disease before tissue biopsy. Through pilot study, a new clinical application for Mohs micrographic surgery is presented. Clinical obstacles were addressed and a new system was tested with ex vivo specimens and validated with histopathology. An improved method for imaging is presented enabling up to a 40% increase in signal-to-noise and a 100% increase in system dynamic range. In addition, a method and system is presented for spectral control of intraoperative illumination that may circumvent the need to turn off the lights during optical imaging. Finally, system measurements were validated and standardized with two-photon microscopy and reference dye for future multi-site clinical trial.

Although currently DOCI values are only an approximation to the complex nature of heterogenous fluorescence lifetime decay, the method permits generation of meaningful contrast between neoplastic and surrounding normal tissue that may aid clinicians and lead to improved patient outcomes. The results regarding clinical performance of Dynamic Optical Contrast Imaging should be considered as preliminary and not be used for medical diagnosis or treatment before appropriate regulatory and medical approval.