MRI detects therapeutic effects in weanling Niemann-Pick type C mice

To noninvasively evaluate the early effects of Niemann-Pick type C (NPC) disease, diffusion tensor imaging (DTI) was carried out in the brains of very young (23-day-old) mice. The diffusion of water in white matter tracts of Npc1^-/- mice at this young age was already abnormal, exhibiting decreased anisotropy, as quantified by fractional anisotropy (FA), compared with their wild-type littermates, the controls. Postmortem histological staining revealed myelin de.ciencies in Npc1^{-/ -} mice, consistent with the reduction in FA measured vivo. Beneficial effects of treatment with allopregnanolone and/ or 2 hydroxypropyl-beta-cyclodextrin was also detectable at this age by FA, which correlated with increased myelination as seen by histology. This is the earliest detection of a therapeutic effect in Npc1^-/- mice.