Real-time reactive oxygen species dosimetry for pleural photodynamic therapy

Photodynamic therapy (PDT) outcomes depend critically on the dynamic interactions between light, photosensitizer concentration, and tissue oxygen. While traditional dosimetry relies on prescribed light fluence, reactive oxygen species (ROS) explicit dosimetry represents the most accurate predictor of treatment efficacy. However, clinical implementation has been limited by the lack of real-time tissue oxygenation monitoring capabilities during treatment. We developed and validated an integrated real-time ROS dosimetry system that combines our previously reported 8-channel photosensitizer concentration monitoring with diffuse correlation spectroscopy (DCS) blood flow measurements to enable comprehensive ROS calculations during pleural PDT. The system utilizes isotropic detectors for simultaneous light fluence and Photofrin fluorescence measurements, while custom DCS contact probes measure tissue blood flow as a surrogate for oxygen delivery. Our preclinical validation established a conversion factor of 1.5 × 109μMs−1cm2 to correlate DCS-measured blood flow indices with tissue oxygen concentrations. The integrated system features a MATLAB-based user interface displaying instantaneous photosensitizer concentrations, blood-flow-derived oxygen levels, and cumulative ROS dose calculations across eight anatomical locations. Validation using clinical datasets from 20 patients demonstrated agreement within 10% between real-time and post-treatment analysis. This work represents the first clinical implementation of real-time ROS explicit dosimetry, providing physicians with immediate feedback on treatment efficacy for more personalized photodynamic therapy treatments.