title: Detecting the effects of Fabry disease in the adult human brain with diffusion tensor imaging and fast bound-pool fraction imaging.
abstract: BACKGROUND
  To identify quantitative MRI parameters associated with diffusion tensor imaging (DTI) and fast bound-pool fraction imaging (FBFI) that may detect alterations in gray matter and/or white matter in adults with Fabry disease, a lysosomal storage disorder.
  
  
  METHODS
  Twelve healthy controls (mean age ± standard deviation: 48.0 ± 12.4 years) and 10 participants with Fabry disease (46.7 ± 12.9 years) were imaged at 3.0 Tesla. Whole-brain parametric maps of diffusion tensor metrics (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) and the bound-pool fraction (f) were acquired. Mean voxel values of parametric maps from regions-of-interest within gray and white matter structures were compared between cases and controls using the independent t-test. Spearman's rho was used to identify associations between parametric maps and age.
  
  
  RESULTS
  Compared with controls, the left thalamus of Fabry participants had an increase in FA (0.29 ± 0.02 versus 0.33 ± 0.05, respectively; P = 0.030) and a trend toward an increase in ADC (0.73 ± 00.02 versus 0.76 ± 0.03 μm(2) /s, respectively; P = 0.082). The left posterior white matter demonstrated a reduction in f (10.45 ± 0.37 versus 9.00 ± 1.84%, respectively; P = 0.035), an increase in ADC (0.78 ± 0.04 versus 0.94 ± 0.19 μm(2) /s, respectively; P = 0.024), and a trend toward a reduction in FA (0.42 ± 0.07 versus 0.36 ± 0.08, respectively; P = 0.052). Among all parameters, only f measured in the left posterior white matter was significantly associated with age in Fabry participants (rho = -0.71; P = 0.022).
  
  
  CONCLUSIONS
  Parameters derived from DTI and FBFI detect Fabry-related changes in the adult human brain, particularly in the posterior white matter where reductions in myelin density as measured by FBFI appear age related.
authors.affiliation: Departments of Neurological Surgery and Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.|Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Hunter R
authors.initials: HR
authors.lastname: Underhill
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Golden-Grant
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Lauren T
authors.initials: LT
authors.lastname: Garrett
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Uhrich
authors.affiliation: Departments of Pediatrics and Neurology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Zielinski
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Scott
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D000795:Fabry Disease / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D049690:History, Ancient; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology*
keywords: Fabry disease; bound-pool fraction; diffusion tensor imaging; magnetization transfer; quantitative MRI; white matter disease