Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18...

Area of Science:

• Neuroimaging
• Immunology
• Neurology

Background:

• 18-kDa translocator protein (TSPO) PET imaging with 18F-PBR06 detects microglial activation (MA) in multiple sclerosis (MS).
• Understanding the impact of disease-modifying treatments (DMTs) on MA and its correlates is crucial for MS management.

Purpose of the Study:

• To develop individualized mapping of MA using 18F-PBR06 PET.
• To assess the efficacy of high-efficacy DMTs in reducing MA.
• To identify clinical, radiological, and serological correlates of residual MA.

Main Methods:

• 30 18F-PBR06-PET scans in 22 MS patients and 8 healthy controls (HCs).
• Calculation of logarithmically transformed glial activity load on PET (lnGALP) scores.
• Comparison of lnGALP between MS patients and HCs, and between DMT groups; correlation with clinical, biomarker, and imaging data.

Main Results:

• MS patients exhibited higher cortical gray matter (CoGM) and white matter (WM) lnGALP scores than HCs.
• High-efficacy DMTs significantly reduced lnGALP but did not normalize it compared to HCs.
• In H-DMT patients, CoGM lnGALP correlated with disability, fatigue, serum GFAP, and inversely with cortical thickness.

Conclusions:

• High-efficacy DMTs decrease but do not eliminate MA in MS patients.
• Residual MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration.
• 18F-PBR06 PET offers a feasible imaging biomarker for evaluating "smoldering" inflammation in MS.