title: Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington's Disease.
abstract: BACKGROUND
  Huntington's disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease's characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum.
  
  
  OBJECTIVE
  To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period.
  
  
  METHODS
  In 48 early-stage HD patients and 36 controls from the multi-site PADDINGTON project, diffusion tensor imaging (DTI) was employed to measure changes in fractional anisotropy (FA) and axial (AD) and radial diffusivity (RD) in 24 white matter regions-of-interest (ROIs).
  
  
  RESULTS
  Cross-sectional analysis indicated widespread baseline between-group differences, with significantly decreased FA and increased AD and RD found in HD patients across multiple ROIs. Longitudinal rates of change differed significantly between HD patients and controls in the genu and body of corpus callosum, corona radiata and anterior limb of internal capsule. Change in RD in the body of the corpus callosum was significantly associated with baseline disease burden, but other clinical associations were not significant.
  
  
  CONCLUSIONS
  We detected subtle longitudinal white matter changes in early HD patients. Progressive white matter abnormalities in HD may not be uniform throughout the brain, with some areas remaining static in the early symptomatic phase. Longer assessment periods across disease stages will help map this progressive trajectory.
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL, London, WC1N 3BG, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gregory
authors.affiliation: UCL Institute of Neurology, University College London, UK.|Computational, Cognitive & Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: Cole
authors.affiliation: Department of Medical Statistics, London School of Hygiene & Tropical Medicine London, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Farmer
authors.affiliation: UCL Institute of Neurology, University College London, UK.
authors.forename: Elin M
authors.initials: EM
authors.lastname: Rees
authors.affiliation: Department of Neurology, Leiden University Medical Centre, 2300RC Leiden, The Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Sprengelmeyer
authors.affiliation: Department of Genetics and Cytogenetics, INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Landwehrmeyer
authors.affiliation: Centre for Medical Image Computing, University College London, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: UCL Institute of Neurology, University College London, UK.
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.affiliation: UCL Institute of Neurology, University College London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.affiliation: Department of Medical Statistics, London School of Hygiene & Tropical Medicine London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Frost
authors.affiliation: UCL Institute of Neurology, University College London, UK.|IXICO Plc., London, UK.
authors.forename: Nicola Z
authors.initials: NZ
authors.lastname: Hobbs
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology
keywords: Huntington’s disease; diffusion tensor imaging; longitudinal; symptomatic