title: Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis.
abstract: 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 [11C]PBR28 in MS over a range of brain inflammatory burden.
  
  
  METHODS
  A total of 23 patients were studied. TSPO PET imaging with [11C]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
  [11C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [11C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [11C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [11C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures.
  
  
  CONCLUSIONS
  MRS [ myo-inositol] and PET [11C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [11C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Gourab
authors.initials: G
authors.lastname: Datta
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Ines R
authors.initials: IR
authors.lastname: Violante
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Gregory
authors.initials: G
authors.lastname: Scott
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Zimmerman
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Andre
authors.initials: A
authors.lastname: Santos-Ribeiro
authors.affiliation: Imanova Ltd, Imperial College London, London, UK/Centre for Neuroimaging Sciences, King's College London, London, UK.
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK/manova Ltd, Imperial College London, London, UK.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Malik
authors.affiliation: Queen Square Multiple Sclerosis Centre, Institute of Neurology, University College London, London, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*; D055815:Young Adult
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human; D007294:Inositol
keywords: MRI; Multiple sclerosis; biomarkers; glia