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Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

Authors
  • Datta, Gourab1
  • Colasanti, Alessandro1, 2
  • Rabiner, Eugenii A3, 4
  • Gunn, Roger N1, 3
  • Malik, Omar1
  • Ciccarelli, Olga5, 6
  • Nicholas, Richard1
  • Van Vlierberghe, Eline7
  • Van Hecke, Wim7
  • Searle, Graham1, 3
  • Santos-Ribeiro, Andre1
  • Matthews, Paul M1, 8
  • 1 Division of Brain Sciences, Imperial College London, UK.
  • 2 Department of Neuroscience, Brighton and Sussex Medical School, UK.
  • 3 Imanova Ltd, London, UK.
  • 4 Centre for Neuroimaging Sciences, King's College, London, UK.
  • 5 Queen Square Multiple Sclerosis Centre, University College London, Institute of Neurology, London, UK.
  • 6 NIHR University College London Hospitals Biomedical Research Centre, London, UK.
  • 7 Icometrix, Boston, USA.
  • 8 UK Dementia Research Institute, The Medical Research Council, One Kemble Street, London WC2B 4AN, UK.
Type
Published Article
Journal
Brain
Publisher
Oxford University Press
Publication Date
Nov 01, 2017
Volume
140
Issue
11
Pages
2927–2938
Identifiers
DOI: 10.1093/brain/awx228
PMID: 29053775
Source
Medline
Keywords
License
Unknown

Abstract

Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnetization transfer ratio for all of the patients combined explained over 90% of the variance in enlarging lesion volume over the subsequent 1 year. Glial activation in white matter assessed by translocator protein PET significantly improves predictions of white matter lesion enlargement in relapsing remitting patients and is associated with greater brain atrophy in secondary progressive disease over a period of short term follow-up.

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