Association of white matter injury and neuroinflammation in the post-acute phase after ischemic stroke using [18F]FEPPA-PET/MRI

Abstract

Background: Cerebral white matter (WM) injury after ischemic stroke is associated with post-stroke cognitive impairment (PSCI), however, the interaction between sustained neuroinflammation and post-stroke WM injury is not well understood. Hybrid PET/MRI can provide insight into pathophysiological mechanisms linking chronic neuroinflammation, ischemic WM injury, and PSCI. Using PET/MRI, this study investigated the relationship between [18F]FEPPA standardized uptake value ratio (SUVr) measurements of glial activation and diffusion tensor imaging (DTI) measurements of microstructure integrity in brain WM regions in the chronic phase at 6-months after acute ischemic stroke. Results: [18F]FEPPA-PET, DTI, and T2-weighted FLAIR were acquired at 6-months post-stroke in 19 elderly humans (seven females; mean age = 76 ± 5 years) with confirmed first-ever acute ischemic stroke using hybrid PET/3T-MRI. Index infarcts, chronic (incidental, covert) infarcts, and WM hyperintensities were manually segmented on FLAIR and excluded from the imaging analysis. Pearson correlation was conducted to assess the association between [18F]FEPPA-SUVr and DTI measurements in WM regions commonly implicated in PSCI. [18F]FEPPA-SUVr was elevated in brain regions ipsilateral to the index infarct at 6-months post-stroke, and these increases correlated with decreases in fractional anisotropy in several WM pathways linked to PSCI, including right superior longitudinal fasciculus (SLF) III (r = -0.82, p < 0.0001), right anterior thalamic radiation (r = -0.61, p = 0.006), and right arcuate fasciculus (r = -0.56, p = 0.01). Elevated [18F]FEPPA-SUVr was also associated with increased mean diffusivity (r = 0.69, p < 0.001), axial diffusivity (r = 0.55, p = 0.02), and radial diffusivity (r = 0.74, p < 0.001) in right SLF III. Conclusions: This study found an association between elevated post-acute glial activation (neuroinflammation) and reduced microstructure integrity in brain WM pathways ipsilateral to ischemic infarcts and remote from WM lesions at 6-months post-stroke. Hybrid PET/MRI is promising to be a valuable tool for probing post-acute neuroinflammation and associated changes in cerebral WM pathways following ischemic stroke.