title: Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.
abstract: BACKGROUND
  Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two.
  
  
  METHODS
  40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others.
  
  
  RESULTS
  Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05).
  
  
  CONCLUSIONS
  The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects.
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Nicola Z
authors.initials: NZ
authors.lastname: Hobbs
authors.forename: James H
authors.initials: JH
authors.lastname: Cole
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Farmer
authors.forename: Elin M
authors.initials: EM
authors.lastname: Rees
authors.forename: Helen E
authors.initials: HE
authors.lastname: Crawford
authors.forename: Ian B
authors.initials: IB
authors.lastname: Malone
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.forename: Reiner
authors.initials: R
authors.lastname: Sprengelmeyer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Bernhard
authors.initials: B
authors.lastname: Landwehrmeyer
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: Chris
authors.initials: C
authors.lastname: Frost
keywords: Diffusion; Huntington's disease; MRI; Volumetric