3D Reactive Oxygen Species Dosimetry in Pleural Photodynamic Therapy: Integration of Macroscopic Kinetic Modeling and Deformable Registration

Photodynamic therapy (PDT) is a promising treatment for pleural malignancies, yet accurate dosimetry remains challenging due to complex cavity geometries and the need to protect surrounding critical structures. The reactive oxygen species ([ROS]rx) generated during treatment serve as a direct predictor of therapeutic efficacy. We developed a finite element model using COMSOL Multiphysics to simulate macroscopic photophysical kinetics, using clinical data inputs, including light fluence derived from a navigation system and patient-specific photosensitizer concentrations. Crucially, we integrated a deformable image registration framework to align intra-operative navigation data with pre-treatment CT scans, enabling the calculation of [ROS]rx dose accumulation in critical Organs at Risk (OARs), such as the lung, heart, and esophagus. The model successfully reconstructed 3D [ROS]rx distributions for multiple clinical cases. Point-to-point comparison at 32 detector locations across ten patients showed strong agreement between COMSOL-simulated and clinically calculated [ROS]rx (mean percentage difference 0.6 ± 5.8%), while volume-averaged values differed by −6.0%, reflecting the enhanced spatial coverage of the 3D model relative to discrete sampling. The two-stage deformable registration improved CT-to-navigation surface alignment from HD95 = 4.08 mm to 1.78 mm (56.4% reduction) and MSD = 1.77 mm to 0.68 mm (61.5% reduction), enabling the first patient-specific mapping of [ROS]rx onto OAR structures. This study demonstrates the feasibility of a comprehensive 3D dosimetry system for pleural PDT. By integrating kinetic modeling with deformable registration, we provide a robust platform for evaluating treatment efficacy and ensuring OAR safety, paving the way for eventual integration into treatment planning and real-time feedback.