Local pressure as a dominant hemodynamic driver of wall enhancement in anterior communicating artery aneurysms: a facet-level computational fluid dynamics and vessel wall imaging analysis.

Background: Size-based risk stratification often overlooks small but unstable intracranial aneurysms (IAs). Aneurysm wall enhancement (AWE) on vessel wall imaging (VWI) is a validated marker of wall instability, yet the local hemodynamic drivers of this pathology, particularly in complex anterior communicating artery (ACoA) aneurysms, remain incompletely characterized. This study leverages a combined computational fluid dynamics (CFD)-VWI approach to characterize the mechanobiological coupling between local hemodynamics and quantitative wall remodeling in ACoA aneurysms. Methods: We retrospectively analyzed 24 patients harboring 25 ACoA aneurysms. A Vector-Integrated Surface Parametrization (VISP) pipeline achieved sub-voxel sampling density [through adaptive interpolation rather than imaging resolution beyond the native 0.6 mm magnetic resonance imaging (MRI) voxel] for co-registration of CFD and 3T-VWI, with wall enhancement defined at a contrast ratio (CR) ≥0.6. To identify hemodynamic drivers of enhanced wall thickness (EWT) while explicitly accounting for within-patient hierarchical clustering, four complementary analytical frameworks were applied in parallel: (I) intra-patient paired bootstrap tests (2,000 resamples) comparing enhanced and non-enhanced wall segments within each of the 13 AWE-positive patients; (II) a multivariate linear mixed model (LMM) with patient-level random intercepts for EWT severity (n=12,473 enhanced segments); (III) generalized estimating equations (GEEs) with cluster-robust variance for AWE presence (n=157,284 segments); and (IV) ensemble machine-learning models (Random Forest and XGBoost) interpreted via Shapley Additive exPlanations (SHAP) values across segment-level, patient-centered, and patient-level GroupKFold cross-validation (CV). Cross-patient generalization of EWT prediction was disclosed separately as an out-of-sample analysis. Results: Focal AWE was identified in 14 of 25 aneurysms (13 patients), spatially coinciding with hemodynamic stagnation zones. Enhanced segments exhibited significantly lower local Pressure Conclusions: We present a facet-level CFD-VWI pipeline that achieves sub-voxel sampling density for spatially mapping local hemodynamics onto quantitative wall remodeling in ACoA aneurysms on a clinical 3T platform. Across four independent hierarchical analyses, local Pressure