The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with 11C-PK11195 in acute subcortical stroke

Abstract

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.