Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

Abstract

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development.

High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields

“…The visual appearance of T 2 B maps of the rat brain at 11.7T (Fig. 2) is in agreement with this finding, as slightly higher T 2 B values are observed in WM regions comprising fiber tracts that are known (Figini et al, 2015; Jugé et al, 2016) to run approximately parallel to the direction of the main magnetic field vector (rostral-caudal direction in Fig. 2).…”

Soft tissue rheology and its implications for elastography: Challenges and opportunities

“…However, in the brains of rodents with induced hydrocephalus, oedema appeared to offset increases in brain stiffness as a result of compression from enlarging ventricles, 28 suggesting that high water content softened brain tissue, consistent with observations in rabbits. 29 A complete rheological understanding of the effects of water content on tissue mechanics remains to be elucidated.…”

“…It is likely that multimodal imaging approaches which combine other modalities that measure fluid content of the tissue (e.g. diffusion‐weighted imaging) with elastography will assist in such cases …”

Modulation of Oligodendrocyte Differentiation by Mechanotransduction

“…The maintenance of the progenitor state of rat OPCs was favored by substrates with stiffness similar to rat brain tissues (~6.5 kPa; Juge et al, 2016) functionalized with fibronectin—an ECM protein known to favor the progenitor state of OLs (Colognato et al, 2004). OPC differentiation was improved when cultured on substrates with the same stiffness, but functionalized with laminin-2/merosin (described as promoter of OPC differentiation (Buttery and ffrench-Constant, 1999)), when compared with cells maintained on 6.5 kPa substrates functionalized with poly-D-lysine alone or kept on softer (2.5 kPa) or stiffer (10 kPa or GPa range) substrates.…”