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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
Objective:
Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.
Methods:
Using PET and optimized modeling and segmentation procedures, we investigated cortical (11)C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).
Results:
Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS.
Conclusions:
Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM.
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.
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