The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual "palpation" of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination. magnetic resonance imaging | elasticity imaging | tissue integrity P alpation of the brain, a hands-on experience long exclusive to neurosurgeons and pathologists detecting brain pathology, has recently become a domain for physicists and radiologists: Using magnetic resonance elastography (MRE), it is possible today to noninvasively assess the biomechanical properties of brain parenchyma in vivo. In MRE, viscoelasticity describes the tendency of tissue to resist deformation, thus translating the subjective tactile information gained from palpation into a quantifiable objective measure. These properties can be acquired by analyzing the propagation of low-frequency shear waves, which are mechanically elicited in an organ of interest (1, 2).Recent preliminary studies described distinct viscoelastic characteristics of the brain parenchyma in healthy subjects as well as changes by aging and brain pathology, underlining the applicability and relevance of cerebral MRE (3, 4). During physiological aging, there was evidence for a brain parenchymal "liquification" reflected in the decrease of solid-fluid behavior of the tissue (5). In patients suffering from multiple sclerosis (MS), a significant decrease of cerebral viscoelasticity was noted already in early disease stages compared with healthy controls (6).However, despite a rising collection of in vivo viscoelasticity data, no study has yet directly correlated viscoelastic parameters assessed via MRE with histopathological analyses. Thus, the question on how in vivo mechanical properties translate into cellular and molecular conditions has remained open.Magnetic resonance imaging (MRI) has emerged as most important paraclinical tool for the diagnosis and monitoring of neuroinflammatory diseases like MS, as reflected by current diagnostic ...

The value of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in deriving novel diagnostic and therapeutic input has been subject to recent debate. This study is the first to report a disseminated distribution of plaques including cranial nerves, prior to or at early stages of disease in murine adoptive transfer EAE, irrespective of the development of clinical symptoms. We induced EAE by adoptive proteolipid protein-specific T-cell transfer in 26 female SJL/J mice, and applied high-field-strength magnetic resonance imaging (MRI) scans longitudinally, assessing blood-brain barrier (BBB) disruption by gadopentate dimeglumine enhancement. We visualized inflammatory nerve injury by gadofluorine M accumulation, and phagocytic cells in inflamed tissue by very small anionic iron oxide particles (VSOP-C184). MRI was correlated with immunohistological sections. In this study, we discovered very early BBB breakdown of white and grey brain matter in 25 mice; one mouse developed exclusively spinal cord inflammation. Widely disseminated contrast-enhancing lesions preceded the onset of disease in 10 animals. Such lesions were present despite the absence of any clinical disease formation in four mice, and coincided with the first detectable symptoms in others. Cranial nerves, predominantly the optic and trigeminal nerves, showed signal intensity changes in nuclei and fascicles of 14 mice. At all sites of MRI lesions we detected cellular infiltrates on corresponding histological sections. The discrepancy between the disease burden visualized by MRI and the extent of disability indeed mimics the human clinico-radiological paradox. MRI should therefore be implemented into evaluational in vivo routines of future therapeutic EAE studies.

Here we present a method for the simultaneous segmentation of white matter lesions and normal-appearing neuroanatomical structures from multi-contrast brain MRI scans of multiple sclerosis patients. The method integrates a novel model for white matter lesions into a previously validated generative model for whole-brain segmentation. By using separate models for the shape of anatomical structures and their appearance in MRI, the algorithm can adapt to data acquired with different scanners and imaging protocols without retraining. We validate the method using four disparate datasets, showing robust performance in white matter lesion segmentation while simultaneously segmenting dozens of other brain structures. We further demonstrate that the contrast-adaptive method can also be safely applied to MRI scans of healthy controls, and replicate previously documented atrophy patterns in deep gray matter structures in MS. The algorithm is publicly available as part of the open-source neuroimaging package FreeSurfer.