Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis

Mult Scler. 2017 Oct;23(11):1469-1478. doi: 10.1177/1352458516681504. Epub 2016 Dec 7.

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.

Conclusion: 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.

Keywords: MRI; Multiple sclerosis; biomarkers; glia.

MeSH terms

  • Adult
  • Aged
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Female
  • Humans
  • Inositol / metabolism*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Multiple Sclerosis / metabolism*
  • Neuroglia / metabolism*
  • Positron-Emission Tomography / methods*
  • Pyrimidines / metabolism*
  • Receptors, GABA / metabolism*
  • Young Adult

Substances

  • (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
  • Pyrimidines
  • Receptors, GABA
  • TSPO protein, human
  • Inositol