MRI signature in a novel mouse model of genetically induced adult oligodendrocyte cell death

Mueggler, Thomas, Pohl, Hartmut, Baltes, Christof, Riethmacher, Dieter, Suter, Ueli and Rudin, Markus (2012) MRI signature in a novel mouse model of genetically induced adult oligodendrocyte cell death. NeuroImage, 59 (2), 1028-1036. (doi:10.1016/j.neuroimage.2011.09.001). (PMID:21945466)

Abstract

Two general pathological processes contribute to multiple sclerosis (MS: acute inflammation and degeneration. While magnetic resonance imaging (MRI) is highly sensitive in detecting abnormalities related to acute inflammation both clinically and in animal models of experimental autoimmune encephalomyelitis (EAE), the correlation of these readouts with acute and future disabilities has been found rather weak. This illustrates the need for imaging techniques addressing neurodegenerative processes associated with MS.

In the present work we evaluated the sensitivity of different MRI techniques (T2 mapping, macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)) to detect histopathological changes in a novel animal model making use of intrinsic, temporally and spatially controlled triggering of oligodendrocyte cell death. This mouse model allows studying the MRI signature associated to neurodegenerative processes of MS in the absence of adaptive inflammatory components that appear to be foremost in the EAE models. Our results revealed pronounced T2 hyperintensities in brain stem and cerebellar structures, which we attribute to structural alteration of white matter by pronounced vacuolation. Brain areas were found devoid of significant macrophage infiltration in line with the absence of a peripheral inflammatory response. The significant decrease in diffusion anisotropy derived from DTI measures in these structures is mainly caused by a pronounced decrease in diffusivity parallel to the fiber indicative of axonal damage.

Triggering of oligodendrocyte ablation did not translate into a significant increase in radial diffusivity. Only minor decreases in MT ratio have been observed, which is attributed to inefficient removal of myelin debris.

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Contributors

Author: Dieter Riethmacher

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