Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington’s Disease

Article type: Research Article

Authors: Gregory, Sarah^{a; 1; *} | Cole, James H.^{b; c; 1} | Farmer, Ruth E.^d | Rees, Elin M.^b | Roos, Raymund A.C.^e | Sprengelmeyer, Reiner^f | Durr, Alexandra^g | Landwehrmeyer, Bernhard^f | Zhang, Hui^h | Scahill, Rachael I.^b | Tabrizi, Sarah J.^b | Frost, Chris^d | Hobbs, Nicola Z.^{b; i}

Affiliations: [a] Wellcome Trust Centre for Neuroimaging, UCL, London, WC1N 3BG, UK | [b] UCL Institute of Neurology, University College London, UK | [c] Computational, Cognitive & Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK | [d] Department of Medical Statistics, London School of Hygiene & Tropical Medicine London, UK | [e] Department of Neurology, Leiden University Medical Centre, 2300RC Leiden, The Netherlands | [f] Department of Neurology, Ulm University, Ulm, Germany | [g] Department of Genetics and Cytogenetics, INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France | [h] Centre for Medical Image Computing, University College London, UK | [i] IXICO Plc., London, UK

Correspondence: [*] Correspondence to: Sarah Gregory, Wellcome Trust Centre for Neuroimaging at University College London, 12 Queen Square, London, WC1N 3BG, UK. Tel.: +44 020 3448 4366; E-mail: [email protected].

Note: [1] Equal first author.

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.

Keywords: Huntington’s disease, diffusion tensor imaging, longitudinal, symptomatic

DOI: 10.3233/JHD-150173

Journal: Journal of Huntington's Disease, vol. 4, no. 4, pp. 333-346, 2015