Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant
Shiverer is an important model of central nervous system dysmyelination characterized by a deletion in the gene encoding myelin basic protein with relevance to human dysmyelinating and demyelinating diseases. Perfusion fixed brains from shiverer mutant (C3Fe.SWV Mbp^(shi)/Mbp^(shi)n = 6) and background control (C3HeB.FeJ, n = 6) mice were compared using contrast enhanced volumetric diffusion tensor magnetic resonance microscopy with a nominal isotropic spatial resolution of 80 mum. Images were accurately coregistered using non-linear warping allowing voxel-wise statistical parametric mapping of tensor invariant differences between control and shiverer groups. Highly significant differences in the tensor trace and both the axial and radial diffusivity were observed within the major white matter tracts and in the thalamus, midbrain, brainstem and cerebellar white matter, consistent with a high density of myelinated axons within these regions. The fractional anisotropy was found to be much less sensitive than the trace and eigenvalues to dysmyelination and associated microanatomic changes.
Additional Information© 2005 Elsevier Inc. Received 12 April 2005; revised 5 August 2005; accepted 23 August 2005; Available online 5 October 2005. The authors wish to thank Tim Hiltner for mouse perfusions and brain preparation, Natasha Kovacevic, Josette Chen and Mark Henkelmann for invaluable discussions regarding image coregistration and tissue fixation. This work was funded in part by the Human Brain Project (EB00232) with contributions from the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Mental Health, the NCRR (RR13625) and NIHM (MH61223).
Accepted Version - nihms241810.pdf