Increased PK11195 PET binding in the cortex of patients with MS correlates with disability

Marios Politis1, Paolo Giannetti, Paul Su

  • 1Centre for Neuroscience, Hammersmith Hospital, Imperial College London, London. marios.politis@imperial.ac.uk

Neurology
|July 6, 2012
PubMed
Abstract

Insights

Microglial activation in multiple sclerosis (MS) cortical gray matter is measurable in vivo. This activation correlates with patient disability, particularly in secondary progressive MS (SPMS).

Area of Science:

  • Neuroscience
  • Immunology
  • Radiology

Background:

  • Activated microglia are implicated in cortical gray matter demyelination in multiple sclerosis (MS).
  • Assessing microglial activation in vivo is crucial for understanding MS pathology.
  • Cortical gray matter involvement in MS is increasingly recognized.

Purpose of the Study:

  • To evaluate microglial activation in the cortical gray matter of MS patients using Positron Emission Tomography (PET).
  • To explore the relationship between microglial activation and clinical disability measures in MS.
  • To differentiate microglial activation patterns in relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS).

Main Methods:

  • Utilized PET imaging with (11)C-PK11195 (PK11195) tracer to assess microglial activation.
  • Employed optimized modeling and segmentation for quantitative analysis of PK11195 binding.
  • Assessed patient disability using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).

Main Results:

  • MS patients exhibited increased cortical gray matter PK11195 binding compared to controls.
  • PK11195 binding was multifocal, with highest levels in specific cortical regions.
  • Total cortical gray matter PK11195 binding correlated with EDSS scores, especially in SPMS patients.
  • SPMS patients showed additional PK11195 binding increases in distinct gyri.
  • No correlation between PK11195 binding and disability was observed in white matter.

Conclusions:

  • In vivo assessment of microglial activation in MS cortical gray matter is feasible using PET.
  • Microglial activation in MS is heterogeneously distributed within the cortex.
  • Cortical microglial activation is significantly related to clinical disability in MS patients.
  • Findings support the role of enhanced microglial activation in SPMS cortical pathology.