Longitudinal MEMRI analysis of brain phenotypes in a mouse model of Niemann-Pick Type C disease

Abstract

Niemann-Pick Type C (NPC) is a rare genetic disorder characterized by progressive cell death in various tissues, particularly in the cerebellar Purkinje cells, with no known cure. Mouse models for human NPC have been generated and characterized histologically, behaviorally, and using longitudinal magnetic resonance imaging (MRI). Previous imaging studies revealed significant brain volume differences between mutant and wild-type animals, but stopped short of making volumetric comparisons of the cerebellar sub-regions. In this study, we present longitudinal manganese-enhanced MRI (MEMRI) data from cohorts of wild-type, heterozygote carrier, and homozygote mutant NPC mice, as well as deformation-based morphometry (DBM) driven brain volume comparisons across genotypes, including the cerebellar cortex, white matter, and nuclei. We also present the first comparisons of MEMRI signal intensities, reflecting brain and cerebellum sub-regional Mn2+-uptake over time and across genotypes.