title: Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water.
abstract: Myelin loss and axonal damage are both observed in white matter injuries. Each may have significant impact on the long-term disability of patients. Currently, there does not exist a noninvasive biological marker that enables differentiation between myelin and axonal injury. We describe herein the use of magnetic resonance diffusion tensor imaging (DTI) to quantify the effect of dysmyelination on water directional diffusivities in brains of shiverer mice in vivo. The principal diffusion eigenvalues of eight axonal fiber tracts that can be identified with certainty on DTI maps were measured. The water diffusivity perpendicular to axonal fiber tracts, lambda(perpendicular), was significantly higher in shiverer mice compared with age-matched controls, reflecting the lack of myelin and the increased freedom of cross-fiber diffusion in white matter. The water diffusivity parallel to axonal fiber tracts, lambda(parallel), was not different, which is consistent with the presence of intact axons. It is clear that dysmyelination alone does not impact lambda(parallel). The presence of intact axons in the setting of incomplete myelination was confirmed by electron microscopy. Although further validation is still needed, our finding suggests that changes in lambda(perpendicular) and lambda(parallel) may potentially be used to differentiate myelin loss versus axonal injury.
authors.affiliation: Department of Chemistry, Washington University, St. Louis, Missouri 63110, USA. victor@wuchem.wustl.edu
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Sun
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ramsbottom
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
authors.forename: John
authors.initials: J
authors.lastname: Russell
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000175:diagnosis* / Q000473:pathology; D003937:Diagnosis, Differential; D020833:Diffuse Axonal Injury / Q000175:diagnosis / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009413:Nerve Fibers, Myelinated / Q000473:pathology*