This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Task 1: Device Design and Development Under this Task, Science &Engineering Associates (SEA) and its subcontractors and consultants, will develop a novel imaging/light projection system that will mitigate many of the issues associated with photodynamic therapy (PDT). The device will incorporate a Modulating Imaging technique (MI), developed at the Beckman Laser Institute, that spatially maps the native tissue optical properties of the patient at the lesion site and the uptake of photosensitizer. The system will then be able to use this baseline information with SEA projector technology to customize the laser treatment for the patient so that the optimum dose is provided. For this Task, the requirements for these processes will be identified, the system designed, fabricated and provided to the team for test, evaluation and eventual deployment in the clinic for testing on patients. Task 2: Modulated Imaging &PDT Treatment Development Under this task, the team will develop the suite of pre-treatment tissue characterization tests and photosensitizer tests that will be used to develop a customized laser treatment profile during PDT. The MI sequences will be tested on representative phantoms to help verify and improve performance. Visualization tools for the tissue property maps will be developed and implemented. The process by which the tissue optical properties are used to enable the quantitative evaluation of photosensitizer concentration will be developed and tested. After initiation of the clinical testing, the team will evaluate all of the data tissue spectroscopy and photosensitizer maps to develop and improve the methods to produce a treatment plan for optimum laser dose delivery. A primary objective of the program is to develop real-time dosimetry while the PDT treatment is being conducted to provide feedback to the laser projection system. The timeframe to collect data and feedback to the laser projector will be limited, so under this task, we will investigate the most effective tests that can be conducted during the treatment to improve PDT effectiveness. In addition, we will evaluate the use of this data for margin detection for surgical guidance. Task 3: Clinical Evaluation of Device Under this task the team will develop the clinical protocol and obtain approval of the UC Irvine IRB and HRPO. Upon approval the device will be tested on 60 patients that have biopsy-confirmed basal cell carcinoma (BCC). For the first round of testing, we will use the device developed to measure tissue optical properties that effect the PDT treatment process, such as spectral absorption and reduced scattering coefficients, oxy- and deoxyhemoglobin, water and melanin. The second round will add testing to monitor the photosensitizer uptake into the lesion and normal skin via fluorescence analysis, and the last round will focus on the implementation of customized treatment for the patient based upon their individual skin and lesion characteristics. For the last round of testing, the performance of the system will be evaluated by performing surgery one month after PDT.