Evolving biopsy strategies for molecular profiling of brain arteriovenous malformations

Abstract

Brain arteriovenous malformations (BAVMs) are increasingly recognized as dynamic vascular diseases driven by endothelial genetic alterations and dysregulated signaling pathways, rather than as static structural anomalies. Accumulating evidence from both hereditary and sporadic forms of BAVMs has established endothelial signaling dysfunction as a central pathogenic mechanism underlying aberrant angiogenesis, progressive lesion remodeling, and vascular instability that predisposes to hemorrhage. These insights have fundamentally shifted the conceptual framework of BAVMs toward a pathway-driven disease model. Despite this progress, direct access to biologically informative molecular material from living AVM lesions remains limited, posing a major barrier to detailed mechanistic interrogation and the translation of molecular insights into clinical decision-making. Historically, molecular characterization of AVMs has relied almost exclusively on surgically resected tissue, restricting analyses to selected patient populations and frequently reflecting late-stage disease biology. Such approaches provide limited insight into disease initiation, temporal evolution, or treatment-induced molecular changes. Recent advances in minimally invasive biopsy strategies, particularly those leveraging endovascular access, have begun to overcome these limitations by enabling molecular interrogation of AVMs in vivo. In this mini review, we summarize emerging approaches for molecular profiling of AVMs, with a primary focus on BAVMs, while also drawing on relevant studies in extracranial and other arteriovenous malformations that share common endovascular access routes, technical principles, and translational implications.