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 ...

In MR elastography (MRE), periodic tissue motion is phase encoded using motion-encoding gradients synchronized to an externally applied periodic mechanical excitation. Conventional methods result in extended scan time for quality phase images, thus limiting the broad application of MRE in the clinic. For practical scan times, researchers have been relying on one-dimensional or two-dimensional motion-encoding, low-phase sampling and a limited number of slices, and artifact-prone, single-shot, echo planar imaging (EPI) readout. Here, we introduce a rapid multislice pulse sequence capable of three-dimensional motion encoding that is also suitable for simultaneously encoding motion with multiple frequency components. This sequence is based on a gradient-recalled echo (GRE) sequence and exploits the principles of fractional encoding. This GRE MRE pulse sequence was validated as capable of acquiring full three-dimensional motion encoding of isotropic voxels in a large volume within less than a minute. This sequence is suitable for monofrequency and multifrequency MRE experiments. In homogeneous paraffin phantoms, the eXpresso sequence yielded similar storage modulus values as those obtained with conventional methods, although with markedly reduced variances (7.11 ± 0.26 kPa for GRE MRE versus 7.16 ± 1.33 kPa for the conventional spin-echo EPI sequence). The GRE MRE sequence obtained better phase-to-noise ratios than the equivalent spin-echo EPI sequence (matched for identical acquisition time) in both paraffin phantoms and in vivo data in the liver (59.62 ± 11.89 versus 27.86 ± 3.81, 61.49 ± 14.16 versus 24.78 ± 2.48 and 58.23 ± 10.39 versus 23.48 ± 2.91 in the X, Y and Z components, respectively, in the case of liver experiments). Phase-to-noise ratios were similar between GRE MRE used in monofrequency or multifrequency experiments (75.39 ± 14.93 versus 86.13 ± 18.25 at 28 Hz, 71.52 ± 24.74 versus 86.96 ± 30.53 at 56 Hz and 95.60 ± 36.96 versus 61.35 ± 26.25 at 84Hz, respectively).