Comparison of noninvasive photodynamic therapy dosimetry methods using a dynamic model of ALA-PDT of human skin

A numerical model of ALA photodynamic therapy of human skin was used to calculate photosensitizer fluorescence and singlet-oxygen luminescence (SOL) observable at the skin surface during treatment. From the emissions, three practical dose metrics were calculated: the fractional fluorescence bleaching metric (FFBM) given by F(0)/F, where F is photosensitizer protoporphyrin IX (PpIX) fluorescence and F(0) is its initial value, the absolute fluorescence bleaching metric (AFBM) given by F(0)-F, and the cumulative SOL (CSOL). These three metrics can be measured during clinical PDT treatment, but their relation to actual singlet-oxygen distribution in the skin is complex and may depend on treatment parameters such as irradiance. Using the model, the three metrics were compared to the average singlet-oxygen dose in the dermis. Despite the complex dependence of (1)O(2) concentration on depth, a roughly linear correlation was found for all three dose metrics. The correlation for the FFBM was not robust when treatment parameters were varied and this metric was especially sensitive to the initial PpIX concentration and its depth dependence. The AFBM was less sensitive to treatment conditions but CSOL demonstrated the best overall performance.