Dual-threshold adaptive irradiation strategy for vascular-targeted photodynamic therapy based on hyperspectral-photoacoustic dual-modality imaging

Conventional vascular-targeted photodynamic therapy (V-PDT) typically relies on empirically chosen fixed irradiance and exposure times, without accounting for substantial inter-subject variability in photosensitizer kinetics and oxygen supply. As a result, treatment often proceeds under severe hypoxia, where additional light delivery mainly contributes to inefficient overdosing rather than productive photochemistry. To address this limitation, we established a hyperspectral-photoacoustic dual-modality imaging platform. Hyperspectral imaging simultaneously acquires diffuse reflectance and fluorescence spectra, enabling real-time quantitative monitoring of in vivo photosensitizer photobleaching dynamics and blood oxygen saturation, while photoacoustic microscopy provides micrometer-scale visualization of vascular architecture and V-PDT-induced damage. Building on this capability, we propose a physiology-guided, dual-threshold adaptive light-dosing strategy for individualized light delivery. Instead of adhering to a single preset protocol, the system uses both a tissue oxygenation threshold and an in vivo photosensitizer bleaching plateau as biologically meaningful criteria for real-time light modulation and treatment termination. In preclinical studies, this closed-loop, imaging-guided control scheme improved the balance between V-PDT efficacy and treatment time and provided a technical foundation for future patient-specific dose optimization in V-PDT.