Abstract Brain arteriovenous malformations are potentially life-threatening vascular anomalies that pose significant clinical challenges due to their heterogeneous anatomy and unpredictable natural history. Existing risk stratification models largely rely on isolated imaging markers and fail to account for the dynamic spatial-temporal complexity of arteriovenous malformations. Building on our prior work, demonstrating how ontogenesis dictates clinical outcomes of neuroepithelial tumors, we hypothesize that arteriovenous malformations are similarly influenced by developmental processes that define their spatial distribution, vascular architecture, and susceptibility to complications. Here, we present the protocol and pilot data of our multicenter, retrospective and prospective observational study, which introduces a multidimensional approach integrating precise anatomical phenotyping with ontogenetic mapping and the analysis of dynamic structural changes over time. By leveraging unsupervised non-negative matrix factorization, we identified six biologically plausible meta-topologies in our single-center pilot dataset of 416 patients, supporting the feasibility of this approach. We now seek to expand the study into a multicenter effort with both retrospective and prospective enrollment, aiming for a total sample size of approximately 1,000 patients. This expansion is essential to enhance the granularity, reproducibility, and clinical utility of the meta-topologies. Ultimately, the objective of this integrative framework is to facilitate the development of a robust biologically informed risk-stratifying staging system, enhancing personalized treatment strategies and optimizing patient outcomes.
Beyersdorf et al. (Fri,) studied this question.