title: Demyelination increases radial diffusivity in corpus callosum of mouse brain.
abstract: Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating diseases, impairs axonal conduction and can also be associated with axonal degeneration. Accurate assessments of these conditions may be highly beneficial in evaluating and selecting therapeutic strategies for patient management. Recently, an analytical approach examining diffusion tensor imaging (DTI) derived parameters has been proposed to assess the extent of axonal damage, demyelination, or both. The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability of DTI parameters to detect the progression of myelin degeneration and regeneration. Our results demonstrate that the extent of increased radial diffusivity reflects the severity of demyelination in corpus callosum of mouse brain affected by cuprizone treatment. Subsequently, radial diffusivity decreases with the progression of remyelination. Furthermore, radial diffusivity changes were specific to the time course of changes in myelin integrity as distinct from axonal injury, which was detected by betaAPP immunostaining and shown to be most extensive prior to demyelination. Radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage.
authors.affiliation: Department of Radiology, Biomedical MR Laboratory, Washington University School of Medicine, St. Louis, MO 63110, USA. ssong@wustl.edu
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.forename: Tuan Q
authors.initials: TQ
authors.lastname: Le
authors.forename: Shiow-Jiuan
authors.initials: SJ
authors.lastname: Lin
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Sun
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.forename: Regina C
authors.initials: RC
authors.lastname: Armstrong
mesh_terms: D000465:Algorithms; D000578:Amidines; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002614:Chelating Agents; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology*; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D006651:Histocytochemistry; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000473:pathology; D010503:Periodic Acid-Schiff Reaction; D016707:Tissue Fixation
chemical_list: D000578:Amidines; D016229:Amyloid beta-Peptides; D002614:Chelating Agents; C031455:diamidino compound 253-50; D003471:Cuprizone