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

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 18FFEPPA 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. 18FFEPPA-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 18FFEPPA-SUVr and DTI measurements in WM regions commonly implicated in PSCI. 18FFEPPA-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 18FFEPPA-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. 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.