Phenotyping in vivo chronic inflammation in multiple sclerosis by combined 11C-PBR28 MR-PET and 7T susceptibility-weighted imaging

Mult Scler. 2024 Dec;30(14):1755-1764. doi: 10.1177/13524585241284157. Epub 2024 Oct 22.

Abstract

Background: 11C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists.

Objectives: To investigate the ability of 11C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment.

Methods: Based on 11C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity.

Results: Less than half (44%) of non-PRL WM lesions were active on 11C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores.

Conclusion: 11C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume.

Keywords: 7T MRI; Multiple sclerosis; TSPO; positron emission tomography; smoldering lesions.

MeSH terms

  • Adult
  • Carbon Radioisotopes
  • Female
  • Humans
  • Inflammation / diagnostic imaging
  • Inflammation / pathology
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / pathology
  • Phenotype
  • Positron-Emission Tomography*
  • Pyrimidines
  • Receptors, GABA / metabolism
  • White Matter / diagnostic imaging
  • White Matter / pathology

Substances

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