UCSF Pediatric Stroke Research Center

Brain arteriovenous malformations (bAVMs) are dynamic vascular lesions with potential for de novo formation, growth, and recurrence after complete surgical resection and documented angiographic cure – the latter occurring predominantly in the pediatric population. Inflammation and angiogenesis play important roles; yet, the biological and clinical factors mediating bAVM activity and progression to intracranial hemorrhage are not well understood. Prospective imaging studies and development of biomarkers that are sensitive to therapeutic treatment effects and track with disease course are critically needed for optimal management and surveillance of pediatric patients for hemorrhagic stroke prevention. Project 1 aims to identify imaging and biological factors associated with bAVM growth, recurrence, and development of high-risk features in children diagnosed with bAVM. Our study capitalizes on existing infrastructure, and expands on the expertise of our strong multidisciplinary team and the longitudinal cohort of bAVM patients with detailed clinical, genetic, and angioarchitectural data collected as part of the UCSF Brain AVM Project. We will prospectively enroll and follow children diagnosed with bAVM annually at UCSF with timed imaging, blood, and tissue collection to accomplish the proposed aims.  Aim 1 will investigate novel imaging predictors, such as flow and vessel wall enhancement, using quantitative color-coded digital subtraction angiography, 4DFlow phase contrast MRI, and vessel wall imaging. These newer imaging techniques promise improved anatomic characterization and quantification of flow and inflammation that will be correlated with bAVM growth, recurrence, or development of high-risk features, such as venous outflow stenosis, feeding artery or nidal aneurysms, or silent microhemorrhages. Aim 2 will investigate whether changes in bAVM characteristics and high-risk features are associated with inflammatory and angiogenesis protein biomarkers, presence of KRAS somatic mutations in tissue, or differences in gene expression profiles in endothelial cells collected using a novel endovascular sampling method. Our studies will expand knowledge on the biological mechanisms involved in bAVM and high-risk features, and develop highly sensitive imaging modalities for surveillance monitoring that will inform bAVM management in children.