Cortical morphometric similarity alterations and molecular correlates in acute ischemic stroke

Ischemic stroke is associated with distributed cortical structural alterations, but the molecular context of acute-stage morphometric similarity (MS) changes remains unclear. This study aimed to characterize MS alterations in acute ischemic stroke (AIS) and examine their spatial transcriptomic correlates using the Allen Human Brain Atlas.

In this cross-sectional case-control study, 36 patients with first-ever AIS involving the unilateral basal ganglia and/or corona radiata and 36 healthy controls (HCs) were included. Patients were enrolled within 7 days after symptom onset, and magnetic resonance imaging (MRI) was performed in the acute stage. Whole-brain MS networks were derived from multiple cortical morphometric features. Group differences in regional MS were assessed with adjustment for age, sex, education, and infarction volume. Spatial associations between MS alterations and gene expression were examined using partial least squares regression with post-mortem transcriptomic data from the Allen Human Brain Atlas (AHBA). Correlations between regional MS values and plasma metal concentrations were examined in patients with AIS.

AIS patients exhibited regionally heterogeneous MS alterations, with increased MS mainly in the lateral occipital, lingual, postcentral, and pericalcarine cortices, and decreased MS mainly in the superior frontal, precuneus, and superior temporal regions. Imaging-transcriptomic integration showed that these spatial MS changes were associated with gene expression profiles related to neuronal viability, transcriptional co-regulation, and cellular stress-related pathways. After permutation testing and false discovery rate (FDR) correction, significant associations were identified between right precuneus MS and plasma lead (Pb) and cesium (Cs) levels.

These findings identify region-specific MS alterations in AIS and provide spatial transcriptomic context for early post-stroke structural changes.