Adaptive Optimization of Vascular-Targeted Photodynamic Therapy Efficiency Based on Hyperspectral-Photoacoustic...

Objective: To enhance vascular-targeted photodynamic therapy (V-PDT) efficacy by integrating real-time dosimetric monitoring and adaptive irradiance modulation based on dynamic physiological feedback. Impact Statement: This study presents a closed-loop, dual-modality optical imaging-guided V-PDT platform that enables individualized, oxygen-informed irradiance control, improving therapeutic precision and efficiency. Introduction: While V-PDT is a promising, minimally invasive treatment for tumors and vascular abnormalities, its efficacy is often hindered by rapid oxygen depletion under high irradiance, leading to treatment-limiting hypoxia. Accurate, real-time assessment of both photosensitizer concentration and blood oxygenation is essential to guide optimized therapeutic strategies, yet such capability has remained elusive in clinical settings. Methods: We developed a dual-modality imaging system integrating hyperspectral imaging (HSI) and optical-resolution photoacoustic microscopy (OR-PAM). HSI provides real-time, quantitative mapping of blood oxygen saturation and photosensitizer concentration, and OR-PAM provides high-resolution structural imaging of vascular networks. A personalized V-PDT protocol was implemented, where light irradiance was dynamically modulated in response to real-time blood oxygen feedback. Results: Real-time imaging confirmed that dynamic irradiance modulation effectively suppressed treatment-induced hypoxia while preserving therapeutic oxygen availability. The personalized-irradiation protocol significantly improved therapeutic efficacy compared with conventional fixed-irradiance protocols under identical photosensitizer dosage conditions. PAM-based structural analysis further showed that vascular damage strongly correlated with oxygen-informed irradiance adjustments. Conclusion: By integrating real-time dosimetry monitoring and feedback-controlled illumination, this study presents a closed-loop V-PDT strategy that overcomes oxygen depletion, enabling precise and efficient therapy tailored to individual tissue responses.