Myelin deficiencies visualized in vivo: Visually evoked potentials and T2-weighted magnetic resonance images of shiverer mutant and wild-type mice

Abstract

Visually evoked potentials (VEPs) and micromagnetic resonance imaging (μMRI) are widely used as noninvasive techniques for diagnosis of central nervous system (CNS) diseases, especially myelin diseases, such as multiple sclerosis. Here we use these techniques in tandem to validate the in vivo data in mouse models. We used the shiverer mutant mouse, which has little or no CNS myelin, as a test model. These data show that shiverer (MBP^(shi)/MBP^(shi)) has a VEP latency that is 30% longer than that of its wild-type sibling. Surprisingly, the heterozygous (MBP^(shi)/+) mouse, with apparently normal myelin, nevertheless has a 7% increase in its VEP latency vs. wild type. The μMRIs of the same animals show that myelinated white matter is hypointense compared with gray matter as a result of the shorter T2 in myelinated regions of the CNS. T2-weighted images of wild-type and heterozygous shiverer mice show regions of hypointensity corresponding to the major myelinated tracts, including the optic nerve and the optic tract of the CNS, whereas shiverer mice have no regions of low intensity and therefore no detectable myelinated areas. In shiverer mice, μMRI can discern hypomyelination throughout the brain, including the optic tract, and these changes correlate with longer VEP latencies. In addition, VEPs can also detect changes in the molecular make up of myelin that are not discernible with histology or μMR. These data show the potential of using μMRI in combination with VEPs to follow changes in both the quality and the quantity of myelin in vivo. These combined methods would be useful for longitudinal studies and therapy testing.