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Tissue structure and inflammatory processes shape viscoelastic properties of the mouse brain

Millward, JM;Guo, J;Berndt, D;Braun, J;Sack, I;Infante-Duarte, C;

Magnetic resonance elastography (MRE) is an imaging method that reveals the mechanical properties of tissue, modelled as a combination of viscosity and elasticity . We recently showed reduced brain viscoelasticity in multiple sclerosis (MS) patients compared with healthy controls, and in the relapsing-remitting disease model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which these intrinsic tissue properties become altered remain unclear. This study investigates whether distinct regions in the mouse brain differ in their native viscoelastic properties, and how these properties are affected during chronic EAE in C57Bl/6 mice and in mice lacking the cytokine interferon-gamma. IFN-(-/-) mice exhibit a more severe EAE phenotype, with amplified inflammation in the cerebellum and brain stem. Brain scans were performed in the sagittal plane using a 7T animal MRI scanner, and the anterior (cerebral) and posterior (cerebellar) regions analyzed separately. MRE investigations were accompanied by contrast-enhanced MRI scans, and by histopathology and gene expression analysis ex vivo. Compared with the cerebrum, the cerebellum in healthy mice has a lower viscoelasticity, i.e. it is intrinsically softer . This was seen both in the wild-type mice and the IFN(-/-) mice. During chronic EAE, C57Bl/6 mice did not show altered brain viscoelasticity. However, as expected, the IFN(-/-) mice showed a more severe EAE phenotype, and these mice did show altered brain elasticity during the course of disease. The magnitude of the elasticity reduction correlated with F4/80 gene expression, a marker for macrophages/microglia in inflamed central nervous system tissue. Together these results demonstrate that MRE is sensitive enough to discriminate between viscoelastic properties in distinct anatomical structures in the mouse brain, and to confirm a further relationship between cellular inflammation and mechanical alterations of the brain. This study underscores the utility of MRE to monitor pathological tissue alterations in vivo.