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PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke
Published on: June 14, 2018
The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with
Alexander Thiel1, Basia A Radlinska, Caroline Paquette
1Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada. alexander.thiel@mcgill.ca
Unlabelled:
Animal experiments suggest that 2 different types of activated microglia (AMG) cells occur in the brain after a stroke: local AMG in the area of the infarct and remote AMG, which occurs along affected fiber tracts. We used (11)C-PK11195 PET to image AMG in vivo after stroke in humans in a prospective longitudinal study to investigate the temporal dynamics of AMG and relate local and remote AMG activity to pyramidal tract (PT) damage using diffusion tensor imaging (DTI).
Methods:
Eighteen patients underwent DTI-MRI, (11)C-PK11195 PET, and behavioral testing within 2 wk and 6 mo of acute subcortical stroke. In 12 patients, the PT was affected by the stroke (PT group), and in 6 patients it was not (non-PT group). Standardized volumes of interest (VOIs) were placed along the PT at the level of the brain stem, semioval center, and infarct. Tracer uptake ratios (ipsilateral to contralateral) were calculated for each VOI and related to tract damage (measured as fractional anisotropy ratio) and clinical outcome. Six controls underwent the same protocol but only once.
Results:
In both patient groups, local AMG activity in the infarct was increased initially and significantly decreased over the follow-up period. In contrast, remote AMG was detected only in the PT group in the brain stem along the affected tract and persisted during follow-up. No AMG was observed retrograde to the lesion at any time. Remote AMG activity along the affected PT in the brain stem correlated with initial PT damage as measured by DTI in the same tract portion. Local AMG activity in the infarct correlated with anterograde PT damage only at follow-up. After controlling for PT damage, initial AMG activity in the brain stem showed a positive correlation with clinical outcome, whereas persisting AMG activity in the infarct tended to be negatively correlated.
Conclusion:
DTI-guided (11)C-PK11195 PET in acute subcortical stroke demonstrates differential temporal dynamics of local and remote AMG. Activity of both types related to anterograde PT damage as measured by DTI and might contribute differently to clinical outcome.
Insights
Activated microglia (AMG) cells in stroke brains show distinct local and remote patterns. Remote AMG along fiber tracts correlates with damage and influences patient outcomes after stroke.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Animal studies suggest two types of activated microglia (AMG) cells post-stroke: local (infarct) and remote (fiber tracts).
- Understanding the in vivo dynamics of these AMG populations in humans is crucial for stroke recovery research.
Purpose of the Study:
- To investigate the temporal dynamics of local and remote activated microglia (AMG) cells in human stroke patients.
- To correlate AMG activity with pyramidal tract (PT) damage using diffusion tensor imaging (DTI) and assess its impact on clinical outcomes.
Main Methods:
- Prospective longitudinal study using (11)C-PK11195 PET and DTI-MRI in 18 acute subcortical stroke patients and 6 controls.
- Patients were assessed within 2 weeks and 6 months post-stroke, with analysis of AMG activity and PT damage (fractional anisotropy ratio).
Main Results:
- Local AMG in the infarct decreased over time, while remote AMG in the brainstem persisted in patients with pyramidal tract (PT) damage.
- Remote AMG correlated with initial PT damage; local AMG correlated with anterograde PT damage later.
- Initial remote AMG activity positively correlated with clinical outcome, while persisting local AMG showed a negative correlation.
Conclusions:
- DTI-guided (11)C-PK11195 PET reveals distinct temporal patterns for local and remote AMG post-stroke.
- Both AMG types relate to anterograde PT damage, suggesting differential roles in stroke recovery and clinical outcomes.
