Anisotropic light propagation in human brain white matter

Year: 2025

Authors: Pini E., Di Meo D., Costantini I., Sorelli M., Bradley S., Wiersma D.S., Pavone F.S., Pattelli L.

Autors Affiliation: Ist Nazl Ric Metrolog, Turin, Italy; European Lab Nonlinear Spect, Sesto Fiorentino, Italy; Univ Florence, Dept Biol, Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, Sesto Fiorentino, Italy; CNR, Natl Inst Opt, Sesto Fiorentino, Italy.

Abstract: 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.

Journal/Review: NEUROPHOTONICS

Volume: 12 (4)      Pages from:   to:

More Information: This work was partially funded by the European Union’s NextGenerationEU Programme with the I-PHOQS Research Infrastructure [Grant Nos. IR0000016, ID D2B8D520, and CUP B53C22001750006] Integrated infrastructure initiative in Photonic and Quantum Sciences. E.P. acknowledges financial support from Sony Europe B.V. L.P. acknowledges the CINECA award under the ISCRA initiative, for the availability of high-performance computing resources and support (ISCRA-C ARTTESC2). This project received funding from the General Hospital Corporation Center of the National Institutes of Health under award number U01 MH117023 and BRAIN CONNECTS (award number U01 NS132181). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, USA. From the European Union’s Horizon 2020 research and innovation Framework Programme (Grant No. 654148, Laserlab-Europe), from HORIZON-INFRA-2022-SERV-B-01 EBRAINS 2.0: A Research Infrastructure to Advance Neuroscience and Brain Health Horizon Europe – Framework Programme for Research and Innovation (2021-2027). This research has also been supported by the Italian Ministry for University and Research in the framework of the Advanced Light Microscopy Italian Node of Euro-Bioimaging ERIC and by the European Union – Next Generation EU, Mission 4 Component 1, CUP B53C22001810006, Project IR0000023 SeeLife Strengthening the Italian Infrastructure of Euro-Bioimaging. This work was also supported by Fondazione Cassa di Risparmio di Firenze (project Human Brain Optical Mapping), by RICTD2025-2026 – CUP B97G24000240005, and by LENS and CNR for the technical and scientific support to the Italian National Node FOE 2022 – CUP B53C24004790001 and from the University of Florence (D.R. n. 464 del 02/04/2024) with the project Smart hydrogels with enhanced toughness to enable human brain tissue clearing (SMART-brain), CUP B97G24000240005. The authors further thank Fabrizio Martelli and Alwin Kienle for fruitful discussions, and Ch ristophe Destrieux from the Universite de Tours for providing the human brain specimen analyzed in this study. We express our gratitude to the donor involved in the body donation program of the Association des dons du corps du Centre Ouest, Tours, who made this study possible by generously donating their body to science.
KeyWords: multiple scattering; time-resolved measurements; anisotropic diffusion; scattering tensor; neurophotonics; Monte Carlo simulations
DOI: 10.1117/1.NPh.12.4.045003