Abstract 1122‐000064: Modern Brain Arteriovenous Malformation Models

Introduction : Research of William Hunter’s hypothesized (then discovered) arteriovenous varix (now arteriovenous malformation/AVM) has developed exponentially over the previous quarter‐millennium. 1 Virchow and Luschka’s subsequent contributions (nearly 100 years later) by identifying an AVM of the brain and its congenital nature were two of the first significant developments made in the field. 2,3 AVMs present as an erroneous connection (known as a fistula) between an artery and a vein that bypasses the capillary circulation. 4 The arteries and arterioles contributing to the malformation are known as feeders which connect to the draining veins via a plexiform vascular network known as a nidus. Prior to the design of a synthetic anastomosis coupled with vessel ligation by Spetzler et al, animal models were largely based on embolization or study of the normal anatomy. The animal and early genetic models have been reported on at length and numerous times across the literature, but novel developments spanning the previous decade have ushered in a technological revolution of vascular modeling that warrants discussion and analysis. Methods : Parameterization of a PubMed query to include all literature including the words “brain,” “arteriovenous malformation,” and “model,” yielded 489 articles. Results : After extraction of relevant literature and full‐text screening, 41 articles were chosen for detailed review. Conclusions : While centuries of treatment efforts have progressed from reliance on surgical resection to endovascular approaches (E.g. glue embolization or coiling) and stereotactic radiosurgery (SRS), it was only 43 years ago that the pathology was first modeled in the laboratory. 6 AVM modeling began with an outgrowth of highly specialized, yet not standardized, simulations of feline, canine, murine, primate, swine, ovine, and even leporine origin. These models were motivated by advancements in microsurgical techniques that permitted their creation, development of new technologies to investigate within them, and theories that these AVM representations could support or refute. The first functional model of AVM by anastomosis of the left rostral CCA and caudal JV was developed to study normal perfusion pressure breakthrough theory: its configuration is still employed by animal AVM models in the modern day (though largely in sheep and pigs). The elegance of the CCA‐JV fistula became a component of the now oft‐used RM AVM model which relies on retrograde flow through the RMs via CCA‐JV anastomosis. Similarly, the use of this functional AVM animal model has informed the molecular underpinnings of such lesions as well. Technological innovations outside of neurosurgery have greatly impacted the development of novel AVM models in the form of three‐dimensional flow models printed into silicon models and combined with advanced imaging technology such as 4D flow MRI. Technological developments in preservation solutions, catheterization tools, and imaging technologies have also allowed for advent of the cerebrovascular placental model for testing of treatments such as radiosurgery, glue embolization, coiling, as well as histological assessment of tissue directly after intervention.