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MR elastography-based assessment of matrix remodeling at lesion sites associated with clinical severity in a model of multiple sclerosis

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Item Type:Article
Title:MR elastography-based assessment of matrix remodeling at lesion sites associated with clinical severity in a model of multiple sclerosis
Creators Name:Wang, S. and Millward, J.M. and Hanke-Vela, L. and Malla, B. and Pilch, K. and Gil-Infante, A. and Waiczies, S. and Mueller, S. and Boehm-Sturm, P. and Guo, J. and Sack, I. and Infante-Duarte, C.
Abstract:Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.
Keywords:Magnetic Resonance Elastography, Experimental Autoimmune Encephalomyelitis, Extracellular Matrix, Fibronectin, Gadolinium-Based Contrast Agent, Multiple Sclerosis, Animals, Mice
Source:Frontiers in Neurology
ISSN:1664-2295
Publisher:Frontiers Media SA
Volume:10
Page Range:1382
Date:13 January 2020
Official Publication:https://doi.org/10.3389/fneur.2019.01382
PubMed:View item in PubMed

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