Anisotropic light propagation in human brain white matter.

Significance: Accurate modeling of light diffusion in the human brain is crucial for applications in optogenetics and spectroscopic diagnostic techniques. White matter tissue is composed of myelinated axon bundles, suggesting the occurrence of enhanced light diffusion along their local orientation direction, which however has never been characterized experimentally. Existing diffuse optics models assume isotropic properties, limiting their accuracy. Aim: We aim to characterize the anisotropic scattering properties of human white matter tissue by directly measuring its tensor scattering components along different directions and correlating them with the local axon fiber orientation. Approach: Using a time- and space-resolved setup, we image the transverse propagation of diffusely reflected light across two perpendicular directions in a post-mortem human brain sample. Local fiber orientation is independently determined using light sheet fluorescence microscopy and two-photon fluorescence microscopy. Results: The directional dependence of light propagation in organized myelinated axon bundles is characterized via Monte Carlo simulations accounting for a tensor scattering coefficient, revealing a weaker scattering rate parallel to the fiber orientation. The effects of white matter anisotropy are further assessed by simulating a typical time-domain near-infrared spectroscopy measurement in a four-layer human head model. Conclusions: We provide a first characterization of the anisotropic scattering properties in post-mortem human white matter, highlighting its direct correlation with axon fiber orientation, and opening the way to the realization of quantitatively accurate anisotropy-aware human head 3D meshes for diffuse optics applications.