Vasa vasorum plexus formation in intracranial aneurysm associates with microcalcification and wall thickening

Intracranial aneurysms (IAs) affect about 3% of the population, often leading to catastrophic outcomes upon rupture. Vasa vasorum, microvessels supplying arterial walls, are conjectured to induce inflammation and leakage in IAs that drive adverse remodeling. Using scanning immunofluorescent multiphoton imaging and micro-computed tomography to visualize intact IA specimens, we identified an extensive vasa vasorum plexus in the IA wall. Our quantitative analyses show significant colocalization of vasa vasorum with calcifications, a strong correlation with increased wall thickness (R² = 0.96, P < 0.001), and associations with well-defined multiaxially oriented collagen fibers. These findings highlight a more nuanced role for vasa vasorum, suggesting both adverse and protective remodeling influences, which may critically affect IA rupture risk. Contrary to the prevailing view of vasa vasorum as solely adverse, this study underscores the contribution to IA wall stability and the need to elucidate their functional impact on IA pathophysiology. Hence, these microvessels warrant further investigation for therapeutic targeting.