Durable thrombosis in a rat model of arteriovenous malformation treated with radiosurgery and vascular targeting

Abstract

Radiosurgical treatment of brain arteriovenous malformations (AVMs) has the significant shortcomings of being limited to lesions smaller than 3 cm in diameter and of a latency-to-cure time of up to 3 years. A possible method of overcoming these limitations is stimulation of thrombosis by using vascular targeting. Using an animal model of AVM, the authors examined the durability of the thrombosis induced by the vascular-targeting agents lipopolysaccharide and soluble tissue factor conjugate (LPS/sTF). Stereotactic radiosurgery or sham radiation was administered to 32 male Sprague-Dawley rats serving as an animal model of AVM; 24 hours after this intervention, the rats received an intravenous injection of LPS/sTF or normal saline. The animals were killed at 1, 7, 30, or 90 days after treatment. Immediately beforehand, angiography was performed, and model AVM tissue was harvested for histological analysis to assess rates of vessel thrombosis. Among rats that received radiosurgery and LPS/sTF, induced thrombosis occurred in 58% of small AVM vessels; among those that received radiosurgery and saline, thrombosis occurred in 12% of small AVM vessels (diameter < 200 μm); and among those that received LPS/sTF but no radiosurgery, thrombosis occurred at an intermediate rate of 43%. No systemic toxicity or intravascular thrombosis remote from the target region was detected in any of the animals. Vascular targeting can increase intravascular thrombosis after radiosurgery, and the vessel occlusion is durable. Further work is needed to refine this approach to AVM treatment, which shows promise as a way to overcome the limitations of radiosurgery.