Integrated angiographic hemodynamics, serum inflammatory factors, and untargeted metabolomics characterize a rupture-associated multi-system phenotype in intracranial aneurysms: a cross-sectional study

Intracranial aneurysm rupture is associated with alterations in local hemodynamics, inflammatory activity, and systemic metabolism, yet these processes have largely been investigated separately. We therefore integrated quantitative digital subtraction angiography (QDSA), circulating inflammatory markers, and untargeted serum metabolomics to characterize the multi-system phenotype associated with established unruptured and ruptured intracranial aneurysm states. This single-center retrospective cross-sectional study included 100 patients with a single saccular intracranial aneurysm, comprising 50 patients with unruptured intracranial aneurysms (UIAs) and 50 with ruptured intracranial aneurysms (RIAs). Aneurysm-specific QDSA parameters, serum IL-6, MMP-9, and sTWEAK, and untargeted serum metabolomic profiles were analyzed within the same individuals. Domain-specific scores were constructed and integrated using an equal-weight multi-system score. Primary analyses adjusted for age, sex, bifurcation status, and anterior versus posterior circulation, with robustness assessed using weighting, sensitivity analyses, and strict cross-fitting. RIA was associated with higher aneurysm-specific full width at half maximum, mean transit time, and stasis, together with lower washout, defining a QDSA contrast retention–washout phenotype. The adjusted standardized difference was 1.634 (95% CI, 1.127–2.140) for the QDSA score, 0.980 (95% CI, 0.391–1.569) for the inflammatory score, and 1.592 (95% CI, 1.187–1.996) for the nine-metabolite score. The equal-weight multi-system score showed the largest adjusted group difference (β = 1.956; 95% CI, 1.551–2.361). The inflammation–metabolism relationship also differed between UIA and RIA (adjusted interaction β = −0.606; 95% CI, − 0.996 to − 0.217; P = 0.002). The main associations remained stable across overlap weighting, geometry-related sensitivity analyses, and strict cross-fitting. RIA status was associated with an aneurysm-specific QDSA phenotype characterized by prolonged contrast retention and impaired washout, together with concurrent differences in circulating inflammatory markers and endogenous serum metabolites. Integration of these three domains characterized a broader multi-system pattern and differences in cross-system organization between the established UIA and RIA states.