Influence of the extracellular matrix on water mobility in subcortical gray matter

Abstract

Purpose Water mobility in tissues is related to the microstructure that modulates diffusion and spin relaxation. Previous work has shown that the extracellular matrix (ECM) impacts water diffusion in cartilage. To investigate if similar contributions to image contrast exist for brain, which is characterized by a substantially lower ECM content, diffusion and relaxation were studied in fixed samples from goat and human thalamus before and after enzymatic digestion of ECM compounds. Selected experiments in human corpus callosum were included for comparing subcortical gray matter and white matter. Methods Digestion of matrix components was achieved by treatment with hyaluronidase. Nonlocalized pulsed field gradient measurements were performed with b values between 0.6 and 18,000 s/mm2 at 3T and temperatures between 0°C and 20°C, in addition to T1 and T2 relaxation measurements. The data were fitted to multiexponential models to account for different water compartments. After the measurements, the samples were sliced and stained for ECM‐sensitive markers to verify efficient digestion. Results Microstructural alterations associated with hyaluronan digestion did not lead to measurable effects on water diffusion or T2. However, T1 of the main relaxographic component, attributed to intra‐/extracellular water, decreased by 7%. Conclusion Investigations with very strong gradients did not reveal a detectable effect on water diffusion or T2 after hyaluronan removal, indicating that the brain ECM content is too low to produce a detectable effect. The subtle alteration of T1 upon hyaluronidase treatment might reflect a modulation of intercompartmental water exchange properties.

High-Resolution Magnetization-Transfer Imaging of Post-Mortem Marmoset Brain: Comparisons with Relaxometry and Histology

“…This includes both GM [ e.g ., (Horton & Hocking, 1997)] and WM [ e.g ., (Kozlowski et al ., 2008)] as well as a reduced power of resolving fibers in myelin-dense areas with MBP staining in comparison to Gallyas’ method (Pistorio et al ., 2006). We note that MBP is located in the myelin main period and that low-molecular mass dyes ( e.g ., antibodies to the MBP antigen) do not penetrate the membranes in compact myelin but have to diffuse circumferentially to reach the central laminae of the sheath (Georgi et al ., 2019; Labadie et al ., 2014). An apparently reduced IOD observed with anti-MBP immunostaining in WM regions of known high myelination might, therefore, reflect diffusion-limited access of the antibodies with less efficient staining of central laminae during the staining procedure due to later arrival times.…”

High Angular Resolution Susceptibility Imaging and Estimation of Fiber Orientation Distribution Functions in Primate Brain

“…Interestingly, a closer qualitative voxel-wise comparison of estimated fiber densities suggests—in several instances—that HARSI-based results indicate separated lobes of similar size in two main directions, whereas HARDI-based ODFs appear to point more towards a main direction, with smaller sized lobes existing towards other directions. It is well documented that the water diffusion coefficient (at ambient temperature) is reduced to 30–50% of the in-vivo value (at body temperature) after in-situ perfusion fixation (Sun et al, 2003), with further alterations occurring during the post-mortem interval (i.e., the interval between death and fixation) (D’Arceuil & de Crespigny, 2007; Miller et al, 2011) and during fixation (Georgi et al, 2019; Yong-Hing et al, 2005). Diffusion anisotropy reductions in WM have also been observed (D’Arceuil & de Crespigny, 2007; Miller et al, 2011), which may be related to increased membrane permeability (Shepherd et al, 2009).…”