The association between white matter chronic inflammation and degeneration in multiple sclerosis: A combined C-PBR28 PET-MRI study.

In multiple sclerosis (MS), the interplay between white matter (WM) microglia mediated inflammation and degeneration is still unclear. Using positron emission tomography and diffusion tensor imaging, we assessed the association between WM chronic inflammation and damage in different regions including periventricular, deep, and subcortical WM and their association with clinical measures. Twenty-three people with MS (PwMS) and 13 healthy subjects underwent C-PBR28 imaging on an integrated 3T MR-Positron Emission Tomography system. PwMS showed a significantly higher normalized number of pathological voxels in normal appearing (NA) WM than in lesions (t = 5.51, p < 0.001), and this number was higher in subcortical than in periventricular (t = 5.49, p < 0.001) and deep NAWM (t = 4.94, p < 0.001). Number of pathological voxels in NAWM negatively correlated with fractional anisotropy (FA) in several areas. Expanded-Disability-Status-Scale correlated positively with number of pathological voxels within NAWM (r = 0.47, p < 0.02), while Symbol-Digit-Modalities-Test correlated positively with global NAWM FA (r = 0.57, p < 0.004) and negatively with lesion load (r=-0.55, p < 0.007). In the WM of PwMS, the higher the inflammation the higher the degeneration is, with both processes contributing to clinical measures. Inflammation and degeneration do not necessarily spatially overlap, and both follow a decreasing pattern from CSF, from periventricular surfaces for FA and cortical surfaces for inflammation.