A1 Refereed original research article in a scientific journal

Microglia positron emission tomography and progression in multiple sclerosis: thalamus on fire




AuthorsZeydan, Burcu; Neyal, Nur; Son, Jiye; Schwarz, Christopher G; Kendall, Thomas June C; Morrison, Holly A; Bush, Melissa L; Reid, Robert I; Przybelski, Scott A; Fought, Angela J; Jack, Clifford R; Petersen, Ronald C; Kantarci, Kejal; Lowe, Val J; Airas, Laura; Kantarci, Orhun H

PublisherOxford University Press (OUP)

Publishing placeOXFORD

Publication year2025

JournalBrain Communications

Journal name in sourceBrain Communications

Journal acronymBRAIN COMMUN

Article numberfcaf141

Volume7

Issue3

Number of pages14

eISSN2632-1297

DOIhttps://doi.org/10.1093/braincomms/fcaf141

Web address https://doi.org/10.1093/braincomms/fcaf141

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/498590117


Abstract
Increased innate immune activity promotes neurodegeneration and contributes to progression in multiple sclerosis. This prospective case-control study aims to investigate thalamic microglia density on 18kDa translocator protein PET in patients with multiple sclerosis using a third-generation radioligand, C-11-ER176, and investigate the associations of C-11-ER176 PET uptake with imaging and clinical measures of progression in multiple sclerosis. Patients with multiple sclerosis (n = 50) and controls (n = 55) were prospectively enrolled and they underwent C-11-ER176 PET and MRI including diffusion MRI with neurite orientation dispersion and density imaging. Disease characteristics, expanded disability status scale and multiple sclerosis functional composite scores were obtained in patients with multiple sclerosis. Age at imaging (mean +/- standard deviation: patients = 49.6 +/- 12.9 years, controls = 48.2 +/- 15.4 years, P = 0.63) and sex (female ratio; patients = 72%, controls = 65%, P = 0.47) were not different between the groups. Thalamus C-11-ER176 PET uptake was highest in patients with progressive multiple sclerosis (1.272 +/- 0.072 standardized uptake value ratio), followed by patients with relapsing multiple sclerosis (1.209 +/- 0.074 standardized uptake value ratio) and lowest in controls (1.162 +/- 0.067 standardized uptake value ratio, P < 0.001). Patients with thalamic lesions had higher thalamus C-11-ER176 PET uptake than those without thalamic lesions in both relapsing multiple sclerosis and progressive multiple sclerosis (P < 0.001). In patients with multiple sclerosis, higher thalamus C-11-ER176 PET uptake correlated with lower thalamic volume (r = -0.45, P = 0.001), higher mean diffusivity (r = 0.56, P < 0.001), lower neurite density index (r = -0.43, P = 0.002), lower orientation dispersion index (r = -0.40, P = 0.005) and higher free water fraction (r = 0.42, P = 0.003) in the thalamus. In patients with multiple sclerosis, higher thalamus C-11-ER176 PET uptake also correlated with higher mean diffusivity (r = 0.47, P < 0.001) and lower neurite density index (r = -0.36, P = 0.012) in the corpus callosum. In patients with multiple sclerosis, higher thalamus C-11-ER176 PET uptake correlated with worse expanded disability status scale scores (r = 0.33, P = 0.02), paced auditory serial addition test scores (r = -0.43, P = 0.003) and multiple sclerosis functional composite z-scores (r = -0.46, P = 0.001). Microglia density in the thalamus is highest in patients with progressive multiple sclerosis and is associated with imaging biomarkers of neurodegeneration and clinical disease severity. As a signature imaging biomarker of progression in multiple sclerosis, effectively reflecting the global disease burden, C-11-ER176 PET may aid development and efficacy evaluation of therapeutics targeting microglia.

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Funding information in the publication
This study was funded by the National Institutes of Health [K12 AR084222, P50 AG016574, U01 AG006786], Mayo Clinic Radiology Research Pilot Program, and the Eugene and Marcia Applebaum Award. The funding sources had no role in the study design, collection, analysis, interpretation, or decision to submit this paper.


Last updated on 2025-25-06 at 10:42