Vascular wall structural heterogeneity and hemorrhagic complications during endovascular therapy for brain...

Hemorrhagic complications (HCs) during endovascular therapy (EVT) for brain arteriovenous malformations (bAVM) remain serious adverse events. Although hemodynamic alterations induced by EVT are considered central, the contribution of intrinsic vessel wall architecture is not fully understood. This study characterized vascular structural phenotypes in resected bAVM specimens following EVT and evaluated their association with EVT-related HCs.

Fifty-one patients who underwent surgical resection after EVT were retrospectively included. Digitized hematoxylin-eosin sections were analyzed to extract quantitative vessel-level histomorphological features. After principal component analysis, unsupervised clustering identified structural phenotypes. Phenotype distribution and morphological indices were compared between patients with and without EVT-related HCs. Linear mixed-effects models were used to assess vessel-level differences, and additional exploratory analyses were performed to evaluate the potential influence of clinical factors.

Five vascular phenotypes (Types A-E) were identified. Type B, characterized by increased textural variability and structural heterogeneity, was enriched in the HCs group (FDR-adjusted p = 0.027). Compared with the more homogeneous Type C, Type B showed a lower thickness-to-radius ratio, higher wall thickness coefficient of variation, and smaller minimum wall thickness (all p < 0.001). At the patient-level, wall thickness variability was greater in the HCs group (p = 0.033, Cohen's d = 0.667), whereas Shannon entropy did not differ between groups. Exploratory analyses showed that Type B proportion was not significantly associated with age or treatment intent and remained elevated among patients with HCs within the curative embolization subgroup. Although the association was attenuated after adjustment for age and treatment intent, the effect direction remained unchanged.

Substantial microvascular structural heterogeneity exists within bAVM lesions. The enrichment of a structurally heterogeneous phenotype in patients with HCs suggests that intrinsic vessel wall architecture may be associated with hemorrhagic vulnerability in addition to hemodynamic factors. Further studies are needed to validate these findings and clarify their biological basis.