Realistic Numerical and Analytical Modeling of Light Scattering in Brain Tissue for Optogenetic Applications123

In recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka-Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings. Here, we introduce and study two modified approaches for modeling the distributions of light emanating from a multimode fiber and scattering through tissue, using both realistic numerical Monte Carlo simulations and an analytical approach based on the beam-spread function approach. We demonstrate a good agreement of the new methods' predictions both with recently published data, and with new measurements in mouse brain cortical slices, where our results yield a new cortical scattering length estimate of ∼47 µm at λ = 473 nm, significantly shorter than ordinarily assumed in optogenetic applications.