Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis
| Autor: | Paul M. Matthews, Graham E. Searle, Gourab Datta, Richard Nicholas, Olga Ciccarelli, Wim Van Hecke, Roger N. Gunn, Eline Van Vlierberghe, Alessandro Colasanti, Eugenii A. Rabiner, Andre Santos-Ribeiro, Omar Malik |
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| Přispěvatelé: | GlaxoSmithKline Services Unlimited, Imperial College Healthcare NHS Trust- BRC Funding |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology positron emission tomography Pyridines microglia multiple sclerosis 0302 clinical medicine BINDING Acetamides Image Processing Computer-Assisted Carbon Radioisotopes IN-VIVO medicine.diagnostic_test Brain Organ Size 11 Medical And Health Sciences Middle Aged Multiple Sclerosis Chronic Progressive Magnetic Resonance Imaging White Matter medicine.anatomical_structure Positron emission tomography Female medicine.symptom Life Sciences & Biomedicine Adult medicine.medical_specialty Clinical Neurology ATROPHY White matter Lesion 17 Psychology And Cognitive Sciences 03 medical and health sciences Young Adult Atrophy POSITRON-EMISSION-TOMOGRAPHY Multiple Sclerosis Relapsing-Remitting INFLAMMATION Receptors GABA medicine Brain positron emission tomography Humans CORTICAL DEMYELINATION Science & Technology Neurology & Neurosurgery business.industry translocator protein Multiple sclerosis DISABILITY Neurosciences Magnetic resonance imaging medicine.disease Hyperintensity PATHOLOGY 030104 developmental biology PET Positron-Emission Tomography Neurology (clinical) Neurosciences & Neurology Nuclear medicine business 030217 neurology & neurosurgery |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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