TSPO-PET-measurable neuroinflammation associates with brain atrophy in multiple sclerosis

In neurodegenerative conditions, neuroaxonal damage and tissue destruction lead to central nervous system atrophy. In multiple sclerosis (MS), widespread glial activation can contribute to disease progression and nervous tissue destruction. We aimed to assess the cross-sectional association between brain atrophy and diffuse glial activation.

One-hundred-and-twenty-eight participants with MS (92 relapsing-remitting and 36 progressive MS) and 73 healthy controls (HC) underwent brain MRI and positron emission tomography (PET) using 18-kDa translocator protein (TSPO)-binding radioligand [¹¹C]-PK11195. Associations between [¹¹C]-PK11195 distribution volume ratios (DVR) and brain parenchymal fractions were examined using correlation and multivariable linear regression analyses.

In MS, higher normal-appearing white matter (NAWM) DVR correlated with smaller whole brain (ρ=-0.38, p < 0.001), NAWM (ρ=-0.43, p < 0.001), and thalamus (ρ=-0.42, p < 0.001) volumes. These correlations remained significant after adjustment for age, body mass index, sex, disease modifying treatment status, T2 lesion volume, and MRI field strength. Among HC, higher NAWM DVR values correlated with larger ventricular volume (ρ=0.26, p < 0.05), which remained significant after adjustment for potential confounders.

Increased TSPO-PET measurable glial activation represents an adverse pathological factor in both MS and HC brains and is likely to contribute to the development of brain atrophy.