To investigate temporal brain region specific changes in MRI measures of Theiler’s Murine Encephalomyelitis Virus (TMEV) mice model of chronic demyelination using  9.4T brain MRI imaging.

To investigate temporal brain region specific changes in MRI measures of Theiler’s Murine Encephalomyelitis Virus (TMEV) mice model of chronic demyelination using  9.4T brain MRI imaging.

Two groups of mice (TMEV (n=6) or saline (n=6) intracerebrally injected) were weekly clinically monitored for 26 weeks, starting at 10 weeks post induction (wPI) and scanned with 9.4T MRI. Atlas registration and region segmentation was used to extract MRI measures from basal ganglia, corpus callosum, cortex, and thalamus. White matter (WM) structures, medial corpus callosum (CC), internal capsules (IC), fimbria (Fr) and anterior commissure (AC), were manually labeled to extract voxel-wise mean DTI fractional anisotropy (FA) and mean diffusivity (MD) values.  Brain volume and quantitative susceptibility mapping (QSM) changes were also serially assessed.

Significant differences in DTI measures of TMEV in different WM structures were noted. Amongst all measured structures, Fr FA measures were trending low in acute phase when compared to saline brains starting at 3 wPI, leading to a significant difference at 22 wPI. Similarly, IC FA value was significantly lower at 22 wPI. After a phase of growth driven volume increase in cortex and CC, TMEV brain regions exhibited a significant volume decrease between 10 to 18 wPI. Brain atrophy was associated with an increase in clinical disability scores and abnormal changes in QSM.

Early DTI FA changes are associated with acute inflammation and early demyelination in the TMEV model of MS. Chronic demyelination and axonal loss phase of TMEV is associated with development of brain atrophy and abnormal susceptibility. Further MRI-histology studies are warranted.