Two-stage diffuse fluorescence tomography for monitoring of drug distribution in photodynamic therapy of tumors

Significance: The spatial distribution of the photosensitizing drug concentration is an important parameter for predicting the photodynamic therapy (PDT) outcome. Current diffuse fluorescence tomography methods lack accuracy in quantifying drug concentration. The development of accurate methods for monitoring the temporal evolution of the drug distribution in tissue can advance the real-time light dosimetry in PDT of tumors, leading to better treatment outcomes. Aim: We develop diffuse optical tomography methods based on interstitial fluorescence measurements to accurately reconstruct the spatial distribution of fluorescent photosensitizing drugs in real-time. Approach: A two-stage reconstruction algorithm is proposed. The capabilities and limitations of this method are studied in various simulated scenarios. For the first time, experimental validation is conducted using the clinical system for interstitial PDT of prostate cancer on prostate tissue-mimicking phantoms with the photosensitizer verteporfin. Results: The average relative error of the reconstructed fluorophore absorption was less than 10%, whereas the fluorescent inclusion reconstructed volume relative error was less than 35%. Conclusions: The proposed method can be used to monitor the temporal evolution of the photosensitizing drug concentration in tumor tissue during photodynamic therapy. This is an important step forward in the development of the next generation of real-time light dosimetry algorithms for photodynamic therapy.