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

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Title: Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis
Author(s): Datta, G
Colasanti, A
Rabiner, EA
Gunn, RN
Malik, O
Ciccarelli, O
Nicholas, R
Van Vlierberghe, E
Van Hecke, W
Searle, G
Santos-Ribeiro, A
Matthews, PM
Item Type: Journal Article
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.
Publication Date: 23-Sep-2017
Date of Acceptance: 17-Jul-2017
URI: http://hdl.handle.net/10044/1/55998
DOI: https://dx.doi.org/10.1093/brain/awx228
ISSN: 1460-2156
Publisher: Oxford University Press (OUP)
Start Page: 2927
End Page: 2938
Journal / Book Title: Brain
Volume: 140
Copyright Statement: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Brain following peer review. The version of record Gourab Datta, Alessandro Colasanti, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Eline Van Vlierberghe, Wim Van Hecke, Graham Searle, Andre Santos-Ribeiro, Paul M Matthews; Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis, Brain, Volume 140, Issue 11, 1 November 2017, Pages 2927–2938 is available online at: https://dx.doi.org/10.1093/brain/awx228
Sponsor/Funder: GlaxoSmithKline Services Unlimited
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: COL011953
RD317 -79560
Copyright Statement: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Brain following peer review. The version of record Gourab Datta, Alessandro Colasanti, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Eline Van Vlierberghe, Wim Van Hecke, Graham Searle, Andre Santos-Ribeiro, Paul M Matthews; Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis, Brain, Volume 140, Issue 11, 1 November 2017, Pages 2927–2938 is available online at: https://dx.doi.org/10.1093/brain/awx228
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
multiple sclerosis
microglia
atrophy
translocator protein
positron emission tomography
POSITRON-EMISSION-TOMOGRAPHY
IN-VIVO
CORTICAL DEMYELINATION
TRANSLOCATOR PROTEIN
PET
DISABILITY
INFLAMMATION
PATHOLOGY
ATROPHY
BINDING
atrophy
microglia
multiple sclerosis
positron emission tomography
translocator protein
Acetamides
Adult
Atrophy
Brain
Carbon Radioisotopes
Female
Humans
Image Processing, Computer-Assisted
Inflammation
Magnetic Resonance Imaging
Male
Microglia
Middle Aged
Multiple Sclerosis, Chronic Progressive
Multiple Sclerosis, Relapsing-Remitting
Organ Size
Positron-Emission Tomography
Pyridines
Receptors, GABA
White Matter
Young Adult
Brain
Microglia
Humans
Multiple Sclerosis, Chronic Progressive
Multiple Sclerosis, Relapsing-Remitting
Atrophy
Inflammation
Carbon Radioisotopes
Acetamides
Pyridines
Receptors, GABA
Positron-Emission Tomography
Magnetic Resonance Imaging
Organ Size
Image Processing, Computer-Assisted
Adult
Middle Aged
Female
Male
Young Adult
White Matter
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
multiple sclerosis
microglia
atrophy
translocator protein
positron emission tomography
POSITRON-EMISSION-TOMOGRAPHY
IN-VIVO
CORTICAL DEMYELINATION
TRANSLOCATOR PROTEIN
PET
DISABILITY
INFLAMMATION
PATHOLOGY
ATROPHY
BINDING
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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