J Am Heart Assoc. 2026 Feb 3:e046619. doi: 10.1161/JAHA.125.046619. Online ahead of print.
ABSTRACT
BACKGROUND: Radiomic and transcriptomic analyses have independently identified features linked to mechanical thrombectomy (MT) outcomes. Here, we integrated paired radiomics/transcriptomics of stroke clots to identify neutrophil extracellular trap (NET) enrichment as a predictor of first-pass MT success, assessing the potential to noninvasively detect NET enrichment using prethrombectomy computed tomography imaging.
METHODS: We performed radiomic/transcriptomic analyses of 32 stroke clots retrieved by MT. Clots were segmented from pre-MT computed tomography angiography and noncontrast computed tomography scans, and radiomic features (RFs) were extracted using PyRadiomics. Differentially expressed genes were identified between modified first-pass effect (mFPE) success and failure using the criteria of log(fold-change) ≥1.5 and q <0.05. RFs significantly different between mFPE outcomes were identified. A NET enrichment score was computed from expression data, and RFs that differed significantly between low- and high-NET-enriched clots were selected to construct an RF signature predictive of NET enrichment. Immunofluorescence was completed on clots to provide ground truth NET labeling.
RESULTS: A total of 44 differentially expressed genes were identified between mFPE outcomes. NET formation, neutrophil degranulation, and the NET signaling pathway were among the most enriched gene ontologies in the mFPE failure group, with related genes downregulated in the mFPE success group. Forty RFs were significantly different between mFPE outcomes. Of these, 4 were found to be predictive of clot NET enrichment. Immunofluorescence validated that transcriptomic NET signatures accurately reflected NET presence within clot tissues.
CONCLUSIONS: NET enrichment in clots is associated with reduced mFPE success. With further validation, RFs extracted from prethrombectomy computed tomography imaging may serve as noninvasive biomarkers of clot NET content to aid in preprocedural MT decision-making.
PMID:41631768 | DOI:10.1161/JAHA.125.046619