Modeling Photobleaching and Absorption in Skin Tissue Using Nonlinear Optics: Applications in Laser Techniques and Dosimetry for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) efficacy arises from the interplay of photosensitizer photobleaching, evolving tissue optics, and nonlinear light–tissue interactions. Conventional dosimetry assumes exponential decay and constant optical properties, overlooking depth-dependent bleaching and scattering drift. Here, we present a nonlinear dosimetry framework that integrates first-order bleaching kinetics with Monte Carlo (MC) photon transport, extending the optical penetration depth through a nonlinear expansion. A new metric, the Fluorescence Curvature Index (FCI), classifies regimes as bleaching-dominated (FCI > 0) or surface-confined, multiphoton-dominated (FCI < 0). Using high-resolution MC simulations (10⁶ photons, 0.005 mm steps), bleaching constants ( ), nonlinear coefficients (C, Q), and multiphoton orders ( ), with dose–response sweeps across 10–300 J/cm² ensuring reproducibility. were extracted, including thermal scattering drift terms. Results identified three characteristic regimes: 405 nm and 630 nm with bleaching-dominated clearing, 595 nm with inversion-prone vascular confinement, and multiphoton-driven confinement at high fluence. The consolidated protocol table links penetration depth, bleaching thresholds, and disease targets, providing quantitative guidance for wavelength-specific PDT optimization.