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PAW23 Voxel-based analysis of magnetisation transfer ratio as a potential biomarker in prion diseases
  1. H Hyare1,2,
  2. R Scahill1,2,
  3. J S Thornton1,2,
  4. J Collinge1,2,
  5. D Siddique1,2,
  6. C Carswell1,2,
  7. E De Vita1,2,
  8. T Yousry1,2,
  9. P Rudge1,2,
  10. S Mead1,2
  1. 1The National Prion Unit and Department of Neurodegenarative Disease, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust, London, UK
  2. 2Track-HD Investigators, University College London, London, UK
  1. Correspondence to harpreet.hyare{at}uclh.nhs.uk

Abstract

MRC Prion-1 Trial enabled investigation of longitudinal MRI and cognitive assessments as potential biomarkers for future therapeutic trials in human prion diseases. The cross-sectional data provides opportunity to examine neuroanatomical differences in patients with inherited prion diseases (IPD) and controls. Voxel-based morphometry (VBM) and voxel-based analysis of magnetisation transfer ratio (VBA-MTR) was performed on 17 symptomatic (IS) IPD patients, 6 asymptomatic (AS) mutation carriers and 13 controls (Co). An ANCOVA consisting of diagnostic grouping (Co, IS, AS) with age and total intracranial volume as covariates and a threshold of p<0.001 with false discovery rate (FDR) correction was applied. For VBM, we found significant differences in grey matter (GM) voxels between IS and Co in the basal ganglia, posterior frontal, parietal and cerebellar cortex. No significant differences were found for Co vs AS. However, for the VBA-MTR at the same threshold, more extensive reductions in MTR were observed in IS vs Co. This study reveals the regional specificity of GM volume loss in IPD corresponding to clinical symptoms of ataxia and apraxia. MTR-VBA appears more sensitive than VBM. VBA is useful for investigating structure-function relationships in human prion diseases and has relevance for therapeutic interventions targeting specific brain regions.

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