Microglial activation, white matter tract damage and disability in multiple sclerosis

Objective: To investigate the relationship of in vivo microglial activation to clinical and MRI parameters in multiple sclerosis.

Methods: Secondary progressive (n = 10) or relapsing (n = 10) multiple sclerosis patients, and age matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and [¹¹C](R)-PK11195 radioligand. Clinical assessment, and structural and quantitative MRI including diffusion tensor imaging were performed for comparison.

Results: [¹¹C](R)-PK11195 binding was significantly higher in the normal appearing white matter of secondary progressive vs. relapsing multiple sclerosis patients and healthy controls, in the thalami of secondary progressive patients vs. controls, and in the perilesional area among the progressive compared to relapsing patients. Higher binding in the normal appearing white matter was associated with higher clinical disability and with reduced white matter structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity and with increased white matter lesion load. Increasing age contributed to higher microglial activation in the normal appearing white matter among multiple sclerosis patients, but not in healthy controls.

Conclusions: PET can be used to quantitate microglial activation, which associates with multiple sclerosis progression. This study demonstrates that increased microglial activity in the normal appearing white matter correlates closely with impaired white matter structural integrity, and thus offers one rational pathological correlate to diffusion tensor imaging parameters.