title: Tissue structure and inflammatory processes shape viscoelastic properties of the mouse brain.
abstract: 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-γ(-/-) 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 7 T 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 IFNγ(-/-) mice. During chronic EAE, C57Bl/6 mice did not show altered brain viscoelasticity. However, as expected, the IFNγ(-/-) 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.
authors.affiliation: Institute for Medical Immunology, Charité - Universitätmedizin Berlin, Germany.|Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Millward
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute for Medical Immunology, Charité - Universitätmedizin Berlin, Germany.|Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Dominique
authors.initials: D
authors.lastname: Berndt
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Braun
authors.affiliation: Department of Radiology, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Sack
authors.affiliation: Institute for Medical Immunology, Charité - Universitätmedizin Berlin, Germany.|Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Infante-Duarte
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D055119:Elastic Modulus; D054459:Elasticity Imaging Techniques / Q000379:methods*; D004660:Encephalitis / Q000473:pathology* / Q000503:physiopathology*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical; D014783:Viscosity
keywords: brain; experimental autoimmune encephalomyelitis; inflammation; magnetic resonance elastography; multiple sclerosis