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Background TRACK-HD is an international multi-site study of premanifest and early Huntington's disease (HD) which aims to investigate a range of biomarkers for use in future therapeutic trials. Detecting subtle brain changes in slowly progressive heterogeneous diseases such as HD is a challenge. Manual techniques, the current ‘gold standard’, are time consuming, reliant on the rater skill and impractical for large scale use. Linear registration of serial MRI has successfully been used to detect whole brain and caudate atrophy in HD using the boundary shift integral (BSI). However, it is less robust when applied to structures without brain–CSF boundaries. Non-linear (fluid) registration allows assessment of within subject change across the entire brain so may be applicable to a wider array of structures, thus providing more regionally specific information. Aims To develop and apply a fully automated technique sensitive to 1 year global and regional volumetric changes in premanifest and early HD subjects using fluid registration of serial MRI. Methods/techniques T1 weighted 3T MR images were acquired at baseline and 1 year from 303 subjects (97 controls; 110 premanifest; 96 early HD) in the TRACK-HD study. Regions of interest (ROI) were generated on the baseline scans using the automated FSL software. Fluid registration was used to model within subject voxel level change over the scanning interval and the 1 year volume change was quantified by summing voxel change within each ROI. Results/outcome Preliminary fluid derived results (whole brain and caudate) show good group discrimination, consistent with BSI findings. We will present fluid derived regional and global atrophy rates, group differences and a comparison of our data with BSI results where appropriate. Conclusions We describe a technique which has the potential to provide fully automated global and regional measures of atrophy using multi site data. This may have utility as an outcome measure for future therapeutic trials in HD. [ABSTRACT FROM PUBLISHER]

Background/aims TRACK-HD is a multinational prospective, observational study of Huntington's disease (HD) that aims to examine longitudinal change in premanifest carriers of the mutant HTT gene and subjects with early stage disease (Tabrizi 2009). New data from the first follow-up assessment are reported here, and build on previous findings from baseline 3T MRI and novel clinical, cognitive, quantitative motor, oculomotor and neuropsychiatric assessments. Of 366 subjects enrolled at baseline, 345 (115 controls, 116 premanifest (preHD) and 114 early HD) completed 12 months of follow-up. Statistical analysis was performed to assess annualised change in all modalities. Methods/techniques Annualised rates of global and regional atrophy were higher in both the pre- and early HD groups than in controls (p≤0.007). Whole brain atrophy rates were 0.3%, 0.5% and 0.9%, and caudate atrophy rates 0.6%, 2.0% and 3.5%, in controls, pre and early HD, respectively, over 1 year. Whole brain image analysis techniques also revealed striking cortical and subcortical grey and white matter atrophy over just 1 year even in subjects furthest from predicted disease onset. Quantitative imaging showed significant associations with disease burden and total functional capacity, a widely used clinical measure of disease severity. Cognitive deterioration was detectable in both HD groups. However, rates of decline in cognitive, quantitative motor and oculomotor tasks were greater after onset of motor signs. Results/outcome HD is characterised by a long premanifest state, slow progression and a disease course of around 20 years. After 1 year, we have identified robust change in a range of measures across modalities in both premanifest and early stage HD. Quantitative imaging showed the greatest differentiation across the spectrum of the disease and a number of functional measures of decline were sensitive in early HD with cognitive impairment also detectable in the pre-HD group. Conclusions TRACK-HD is the first multi-site study to report whole brain, regional and subcortical atrophy in premanifest subjects many years from predicted disease onset using 3T MR imaging; and demonstrates the feasibility of obtaining quantifiable endpoints which show robust change over just 1 year thus showing potential as endpoints for future therapeutic trials. [ABSTRACT FROM PUBLISHER]