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.
Tyszka
J Michael
JM
Biological Imaging Center, Division of Biology, California Institute of Technology, 2Q Broad 114-96, 1200 E California Blvd., Pasadena, CA 91125, USA. jmt@caltech.edu
Readhead
Carol
C
Bearer
Elaine L
EL
Pautler
Robia G
RG
Jacobs
Russell E
RE
D000818:Animals; D016880:Anisotropy; D015982:Bias; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics / Q000473:pathology*; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008809:Mice, Inbred C3H; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors