title: Apparent diffusion coefficient reveals gray and white matter disease, and T2 mapping detects white matter disease in the brain in feline alpha-mannosidosis.
abstract: OBJECTIVE
  Methods to locate and identify brain pathology are critical for monitoring disease progression and for evaluating the efficacy of therapeutic intervention. The purpose of this study was to detect cell swelling, abnormal myelin, and astrogliosis in the feline model of the lysosomal storage disease alpha-mannosidosis (AMD) by using diffusion and T2 mapping.
  
  
  METHODS
  Average apparent diffusion coefficient (ADC(av)) and T2 were measured by imaging the brains of five 16-week-old cats with feline AMD on a 4.7T magnet. ADC(av) and T2 data from affected cats were compared with data from age-matched normal cats. Brains were collected from both affected and normal cats following imaging, and histology was compared with quantitative imaging data.
  
  
  RESULTS
  Gray matter from AMD cats demonstrated a 13%-15% decrease in ADC(av) compared with that in normal cats. White matter from AMD cats exhibited an 11%-16% decrease in ADC(av) and a 5%-12% increase in T2 values compared with those in normal control cats. Histologic evidence of neuronal and glial swelling, abnormal myelin, and astrogliosis was consistent with changes in ADC(av) and T2.
  
  
  CONCLUSIONS
  ADC(av) and T2 data can be used to quantify differences in the gray and white matter in the feline AMD brain and may serve as surrogate markers of neuronal swelling, abnormal myelin, and astrogliosis associated with this disease. These studies may be helpful in assessing the efficacy of experimental therapies for central nervous system disease associated with lysosomal storage diseases.
authors.affiliation: W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19105, USA. vite@vet.upenn.edu
authors.forename: C H
authors.initials: CH
authors.lastname: Vite
authors.forename: S
authors.initials: S
authors.lastname: Magnitsky
authors.forename: D
authors.initials: D
authors.lastname: Aleman
authors.forename: P
authors.initials: P
authors.lastname: O'Donnell
authors.forename: K
authors.initials: K
authors.lastname: Cullen
authors.forename: W
authors.initials: W
authors.lastname: Ding
authors.forename: S
authors.initials: S
authors.lastname: Pickup
authors.forename: J H
authors.initials: JH
authors.lastname: Wolfe
authors.forename: H
authors.initials: H
authors.lastname: Poptani
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002371:Cat Diseases / Q000175:diagnosis*; D002415:Cats; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000662:veterinary*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D008363:alpha-Mannosidosis / Q000175:diagnosis* / Q000662:veterinary*