TSPO-PET reveals higher inflammation in white matter disrupted by paramagnetic rim lesions in multiple sclerosis

Identifying the role of compartmentalized inflammation within the central nervous system (CNS) and its association with chronic active lesions is essential for advancing our overall understanding of disease progression in multiple sclerosis (MS). In this study, we explore whether the inflammatory activity is higher in white matter (WM) tracts disrupted by paramagnetic rim lesions (PRLs) and if inflammation in PRL-disrupted WM tracts is associated with disability in people with MS. Forty-four MS patients and 11 healthy controls were included. 18 kDa-translocator protein positron emission tomography (TSPO-PET) with the ¹¹C-PK11195 radioligand was used to measure the neuroinflammatory activity. The Network Modification Tool was used to identify WM tracts disrupted by PRLs and non-PRLs that were delineated on MRI. The Expanded Disability Status Scale was used to measure disability. MS patients had higher inflammatory activity in whole-brain WM compared to healthy controls (p = 0.001). Compared to patients without PRLs, patients with PRLs exhibited higher levels of inflammatory activity in the WM tracts disrupted by any type of lesions (p = 0.02) or PRLs (p = 0.004). In patients with at least one PRL, inflammatory activity was higher in WM tracts highly disrupted by PRLs compared to WM tracts highly disrupted by non-PRLs (p = 0.009). Elevated inflammatory activity in highly disrupted WM tracts was associated with increased disability in patients with PRL (p = 0.03), but not in patients without PRL (p = 0.2). This study suggests that patients with PRLs may exhibit more diffuse WM inflammation in addition to higher inflammation along WM tracts disrupted by PRLs compared to non-PRLs, which could contribute to larger lesion volumes and faster disability progression. Imaging PRLs may serve to identify patients with both focal and diffuse inflammation, guiding therapeutic interventions aimed at reducing inflammation and preventing progressive disability in MS.