This thesis aims to shed light on the biomechanical knowledge of the brain, in particular of its white matter (WM). An extensive, multidisciplinary and bottom-up research has been carried out to understand its micromechanical response focusing on three areas: Corpus Callosum, Corona Radiata and Fornix. Axons and the surrounding matrix with its accessory cells, the two main components of the tissue, have been analysed via Focused Ion Beam Scanning Electron Microscopy (FIB-SEM). Tissue
volumes have been sampled, stained, embedded and imaged to finally be 3D-reconstructed, appearing as unidirectional composite materials. They have been geometrically characterised, creating a location-specific database of: cross-sectional area, diameter, ellipticity and tortuosity of the axons, together with the volume fraction of the volumes. The AFM-enabled nanoindentations investigated the mechanical response of WM. Stress-relaxation experiments have been performed on samples with axons running either parallel or perpendicular to the testing plane. The tissue showed linear viscoelasticity and slight anisotropy at the investigated level. The perpendicular samples showed a higher initial stiffness than parallel samples while the relative change in stiffness after relaxation was higher for the parallel samples than for the perpendicular ones. Finally, micromechanical modelling of the areas was performed. Location-speci c Representative Volume Elements have been created with the geometrical info obtained via FIB-SEM. Via an inverse-modelling approach, using the AFM data, material parameters of the axons and the matrix, the tissue components, have been obtained. The predicted stress-relaxation curves simulated by the finite element analysis showed good agreement with the experimental curves.
The acquired knowledge of the microenvironment is fundamental for a comprehensive microscopical
characterisation of the white matter. It provides important information to reduce
axonal damage during neurosurgery, by predicting the local mechanical response and planning accordingly, and to improve the efficacy and therapeutic reach of Convection Enhanced Delivery, by exploiting the cytoarchitecture, leading to minimal side effects and maximal efficacy of
the treatments.