title: Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I.
abstract: Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-L-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-L-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment.
authors.affiliation: Duke University, Department of Radiology, Durham, NC, USA; Emory University, Department of Radiology, Oncology & Biomedical Engineering, Atlanta, GA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: Duke University, Department of Radiology, Durham, NC, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Chen
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA, USA.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Kan
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA, USA.
authors.forename: Steven Q
authors.initials: SQ
authors.lastname: Le
authors.affiliation: Iowa State University, Department of Animal Science, Ames, IA, USA.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Jens
authors.affiliation: Iowa State University, Department of Animal Science, Ames, IA, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Snella
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA, USA.
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Vondrak
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Yee
authors.affiliation: University of Pennsylvania School of Veterinary Medicine, Department of Clinical Studies, Philadelphia, PA, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Vite
authors.affiliation: University of California, Los Angeles, Departments of Medicine and Biostatistics, Los Angeles, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: University of California, Los Angeles, Departments of Medicine and Biostatistics, Los Angeles, CA, USA.
authors.forename: Lewei
authors.initials: L
authors.lastname: Duan
authors.affiliation: Children's Hospital Orange County, Orange, CA, USA.
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Iowa State University, Department of Animal Science, Ames, IA, USA.
authors.forename: N Matthew
authors.initials: NM
authors.lastname: Ellinwood
authors.affiliation: Saint Louis University School of Medicine, Department of Pathology, Saint Louis, MO, USA.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Guzman
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA.
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Pediatrics, Torrance, CA, USA. Electronic address: pdickson@ucla.edu.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000627:therapeutic use; D007091:Image Processing, Computer-Assisted; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000473:pathology*; D017063:Outcome Assessment, Health Care; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; D012333:RNA, Messenger; D007068:Iduronidase
keywords: Anisotropy; Brain; Diffusion tensor imaging; Enzyme replacement therapy; Hurler; Lysosomal storage disease; Neuroimaging; Scheie