Development and characterization of a combined fluorescence and spatial frequency domain imaging system for real-time dosimetry of photodynamic therapy.

Significance: Current methods of measuring dosimetry for photodynamic therapy (PDT) have proven to be inadequate in their inability to provide accurate, real-time, and spatially resolved monitoring without interrupting the PDT treatment.

Aim: Our goal was to develop and validate a combined treatment and dosimetry system capable of monitoring implicit and explicit dosimetry in real time during non-contact PDT.

Approach: By employing both fluorescence imaging and spatial frequency domain imaging (SFDI), designed with low-cost, off-the-shelf components, the combined imaging system would be able to provide information on the spatial distributions of photosensitizer concentrations, tissue oxygenation, and delivered light dose, all while monitoring the photobleaching dynamics of the photosensitizer. Although the concept behind the combined system is not specific to any one photosensitizer, we focused on designing the system for the endogenous PDT of Gram-positive bacteria which utilizes coproporphyrin III as the photosensitizer.

Results: The overall performance of the system was assessed, with the accuracy, precision, and resolution of the SFDI-derived optical property maps being determined to fall within comparable ranges to other systems, despite the $1.0{\mathrm{mm}}^{-1}$ spatial frequency utilized for the shorter wavelengths. After validating the ability of the system to correct for tissue-like optical properties, and thus produce accurate quantitative fluorescence images, a preliminary assessment of antimicrobial PDT photobleaching dosimetry was performed, and high correlations were found between the fluorescence and PDT outcomes.

Conclusions: Overall, the developed imaging system showcases the potential to enable a more thorough analysis of PDT dosimetry and the impact of different variables on treatment outcomes.