The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging

Diffuse low-grade gliomas display preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Magnetic resonance imaging of one hundred and two low-grade gliomas patients were normalized to/and segmented in MNI space to create a probabilistic infiltration weighted gradient map. Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying high- and low grade of infiltration, (corpus callosum, cingulum, arcuate fasciculus, inferior fronto-occipital fasciculus and cortico-spinal tract), averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration frequency. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration respectively. We detected differences in the infiltration frequency of five major white matter bundles. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis. Regions with high infiltration frequency (HIF) displayed a higher fiber density, smaller fiber diameter but higher myelin thickness and lower axial diffusivity compare compared with low infiltration frequency (LIF) regions. Our results seem to indicate that the fiber diameter, myelin thickness and the possible organization of the fibers are different in HIF compared to LIF regions and may be linked to the preferential location of diffuse low-grade gliomas.