Microglial activation, white matter tract damage, and disability in MS

Area of Science:

• Neuroimaging
• Neuroinflammation
• Multiple Sclerosis Pathophysiology

Background:

• Microglial activation is implicated in multiple sclerosis (MS) pathogenesis.
• Quantifying in vivo microglial activation in MS remains a challenge.
• Understanding the relationship between microglial activity and disease progression is crucial.

Purpose of the Study:

• To investigate the relationship between in vivo microglial activation and clinical/MRI parameters in MS.
• To assess microglial activation using PET and [11C](R)-PK11195.
• To correlate microglial activation with disease severity and white matter integrity.

Main Methods:

• Studied patients with secondary progressive MS (SPMS), relapsing-remitting MS (RRMS), and healthy controls.
• Measured microglial activation via PET with [11C](R)-PK11195.
• Performed clinical assessments and advanced MRI including diffusion tensor imaging (DTI).

Main Results:

• Significantly higher [11C](R)-PK11195 binding in normal-appearing white matter (NAWM) in SPMS vs. RRMS and controls.
• Higher NAWM binding correlated with increased clinical disability and reduced white matter integrity (lower FA, higher MD, increased lesion load).
• Age contributed to higher microglial activation in MS patients' NAWM.

Conclusions:

• PET imaging can quantify microglial activation in MS.
• Increased microglial activity in NAWM is associated with MS progression and impaired white matter integrity.
• This provides a pathological correlate for DTI findings in MS.