Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 23, Issue 11, Pages 1469-1478Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458516681504
Keywords
Multiple sclerosis; glia; biomarkers; MRI
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Funding
- GSK of the Imperial Wellcome-GSK Trust Training Fellowship in Translational Medicine and Therapeutics
- Medical Research Council [MR/N026934/1, MC_PC_17114] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10022] Funding Source: researchfish
- MRC [MC_PC_17114, MR/N026934/1] Funding Source: UKRI
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Background: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. Objective: To explore the in vivo relationships between MRS and PET [C-11]PBR28 in MS over a range of brain inflammatory burden. Methods: A total of 23 patients were studied. TSPO PET imaging with [C-11]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). Results: [C-11]PBR28 uptake and [myo-inositol] were not associated. When the whole cohort was stratified by higher [C-11]PBR28 inflammatory burden, [myo-inositol] was positively correlated to [C-11]PBR28 uptake (Spearman's =0.685, p=0.014). Moderate correlations were found between [C-11]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (=0.535, p=0.009). There were no associations between other imaging or clinical measures. Conclusion: MRS [myo-inositol] and PET [C-11]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [C-11]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
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