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Background: 11 C-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 11 C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment., Methods: Based on 11 C-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 11 C-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 11 C-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: 11 C-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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.A.T. has received research support from Genentech; E.H. has received research support from the NMSS (FG-1507-05459, TA-1905-34039); J.A.S. has consulted for Novartis, Biogen, Celgene, and Genentech; T.G. is a recipient of the Grant for Multiple Sclerosis Innovation, funded by Merck; C.M. has received research support from Genentech. The remaining authors have nothing to disclose.