Monte Carlo simulation of polarization‐sensitive second‐harmonic generation and propagation in biological tissue

Polarization‐sensitive second harmonic generation (p‐SHG) is a nonlinear optical microscopy technique that has shown great promise in biomedicine, such as in detecting changes in the collagen ultrastructure of the tumor microenvironment. However, the complex nature of light‐tissue interactions and the heterogeneity of biological samples pose challenges in creating an analytical and experimental quantification platform for tissue characterization via p‐SHG. We present a Monte Carlo (MC) p‐SHG simulation model based on double Stokes‐Mueller polarimetry for the investigation of nonlinear light‐tissue interaction. The MC model predictions are compared with experimental measurements of second‐order nonlinear susceptibility component ratio and degree of polarization (DOP) in rat‐tail collagen. The observed trends in the behavior of these parameters as a function of tissue thickness, as well as the overall extent of agreement between MC and experimental results, are discussed. High sensitivities of the susceptibility ratio and DOP are observed for the varying tissue thickness on the incoming fundamental light propagation pathway. Polarization‐sensitive second harmonic generation (p‐SHG) is a nonlinear optical microscopy technique that has shown great promise in biomedicine. However, the complex nature of light‐tissue interactions and the heterogeneity of biological samples pose challenges in creating an analytical and experimental quantification platform for tissue characterization via p‐SHG. We present and validate a Monte Carlo p‐SHG simulation model based on double Stokes‐Mueller polarimetry for the investigation of nonlinear light‐tissue interaction.