Neuroinflammation and neurodegeneration coexist in multiple sclerosis (MS), although their inter-relation and specific contribution to disability have not been fully elucidated yet. Inflammation mediated by activated microglia and macrophages may persist beyond the acute phase of MS and is associated with disability progression. Magnetic resonance imaging (MRI) allows to evaluate neurodegeneration in MS, as assessed by grey (GM) and white matter (WM) atrophy and specific WM tracts microstructural alterations. On the other hand, 18kDa translocator protein (TSPO) PET imaging with C-11PBR28 can detect chronic innate immune cell activation.
We hypothesize that MR measures of neurodegeneration and PET measures of chronic neuroinflammation are related in MS, that their relation is specific for brain compartments, and that both impact physical and cognitive disability, although at a different extent.
In this international collaborative study, we will analyze MRI and PET images already acquired at Massachusetts General Hospital (Boston) on 50 MS patients and 25 healthy subjects. This novel multimodal imaging approach combines ultra-high field 7T MRI and simultaneous 11C-PBR28 PET-3T MRI brain acquisition. Anonymized images, demographic and clinical data will be transferred to our laboratory. By using advanced methods of data analysis, T13D and diffusion images will be processed to calculate atrophy in both WM and cortical GM, as well as microstructural damage of WM bundles. PET images will be used to assess areas of increased uptake in both cortical and subcortical GM and WM, including WM tracts. Lastly, multivariate analysis will be performed to model the impact of brain structural damage and chronic neuroinflammation on both physical and cognitive disability. Innovative procedures of tractography and PET uptake analysis will provide novel information on the impact of neuroinflammation and neurodegeneration in different brain compartments on disability in MS.
