Copolymer of 2-hydroxyethyl methacrylate for cerebral arteriovenous malformation: an experimental study

Abstract

To investigate the feasibility of using methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) to embolize cerebral arteriovenous malformations (AVM). Methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) in the ratio of 9:1 were solved in 16% alcohol so as to make a kind of copolymer (CoHEMA). 12 g glass beads 2 mm in diameter were put into a container so as to construct an in vitro model of AVM. The container was connected with a normal saline bottle via microcatheter. CoHEMA, as embolized, was injected through the microcatheter and the diffusion of CoHEMA was observed till the water flow was stopped. CoHEMA was injected through microcatheter into the pharyngeal ascending arteries near the rete mirabile (RMB) tissue, similar to the human AVM, under digital subtraction angiography until satisfactory embolization was obtained, totally 9 RMB tissues in 7 pigs. Five pigs were injected with normal saline as controls. The pigs were killed 2 days, 2 weeks, and 6 months after embolization respectively and the bilateral RMB tissues were taken out to undergo pathological examination. Nine AVM models in vitro were constructed with the copolymer dispersed symmetrically among the glass beads and stopped the fluid across the model effectively. No copolymer adhered to the wall of microcatheter. Nine RMB tissues of 6 pigs were embolized by using CoHEMA. Six of the seven pigs survived the procedure except one died of too fast injection of copolymer in the primary stage. Follow-up angiography was performed in four pigs and found that no recanalization occurred and the copolymer was diffused in the vessels 80-150 microm in diameter. In the specimens obtained 2 days after embolization, neutrophilic granulocytes scattered surrounding the copolymer, suggesting minor inflammatory reaction. In the specimens obtained 2 weeks after embolization no vessel wall damage and morphological change were found except minor inflammatory reaction inside the vessels and surrounding tissues. In the specimens obtained 2 to 6 months after embolization hyperplasia of connective tissue, minor or mediate chronic inflammatory reaction, and giant cell reaction inside the vessels and surrounding tissues. With low viscosity, better biocompatibility, and embolic instability, and easy to be injected through delivery microcatheter, CoHEMA is an excellent non-adhesive embolic material and can be used in embolic treatment of cerebral AVM.