Testing Stenting and Flow Diversion Using a Surgical Elastase-Induced Complex Fusiform Aneurysm Model

Abstract

Background and purpose: Rabbit elastase-induced saccular aneurysms have been commonly used for preclinical testing of endovascular devices, including flow diverters. However, all tested devices have been shown to be capable of aneurysm occlusion with this model. We aimed to create a more challenging model to test and discriminate among neurovascular devices of varying efficacies.

Materials and methods: With a surgical approach that included elastase infusion and balloon dilation, we attempted the creation of complex fusiform aneurysms in 16 rabbits, with standard saccular carotid aneurysms created in 15 other animals. Aneurysms were randomly allocated to one of the following treatments: flow diversion (n = 8), high-porosity stent (n = 6), double high-porosity stent (n = 5), and control (n = 6). Angiographic assessment and pathologic analyses were performed at 3 months.

Results: Creation of complex fusiform and standard saccular aneurysms was successful in 12/16 and 13/15 attempts, respectively. All saccular (n = 4) or complex fusiform (n = 4) aneurysms treated with flow diverters were successfully occluded. Three of 3 saccular compared with 0/2 complex fusiform aneurysms were occluded by double high-porosity stents. One of 3 saccular and 0/3 complex fusiform aneurysms were occluded by a single high-porosity stent. Both aneurysm types shared the same pathologic findings when untreated: The aneurysm wall lacked an elastic layer and smooth muscle cells, while the lumen was lined with neointima of varying thickness. Neointimal coverage of the devices was complete when aneurysms were occluded, while leaks were always associated with aneurysm remnants.

Conclusions: Challenging fusiform aneurysms can be created in rabbits by using a surgical modification of the elastase method.

Fig 1.

Surgical elastase-induced aneurysm creation. A, The right common carotid (black arrow), subclavian (white arrow), and brachiocephalic arteries are encircled with ligatures. B, Under temporary clip occlusion, elastase is injected into the lumen and adventitia of the carotid (both models) and subclavian arteries (fusiform model only). C, A 3F Fogarty balloon catheter is introduced into the carotid artery for angioplasty. D, The distal right carotid artery is occluded, and clips are removed.

Fig 2.

Treatment results (complex fusiform aneurysms). Preimplantation (A1, B1, C1) and 3-month follow-up angiography (A2, B2, C2) and microscopic photography (A3, B3, C3) of complex fusiform aneurysms treated with a single HPS (A), double overlapping HPSs (B), and flow diversion (C) (2 FDs were required). Note angiographic cure after flow diversion, with complete neointimal coverage of the FD. For reference, the diameter of the device wire measures 53 μm.

Fig 3.

Treatment results (saccular aneurysms). Preimplantation (A1, B1, C1) and 3-month follow-up angiography (A2, B2, C2) and microscopic photography (A3, B3, C3) of saccular aneurysms treated with a single HPS (A), double overlapping HPSs (B), and flow diversion (C). Note complete aneurysm occlusion after double HPS placement and flow diversion. For reference, the diameter of the device wire measures 53 μm.

Fig 4.

Pathology of untreated, stented, and flow-diverted fusiform aneurysms. The standard saccular model shows a subclavian of normal diameter with a continuous elastic lamina and no neointima formation (A). In comparison, the complex fusiform aneurysm is composed of a dilated thinned wall with a discontinuous media (black arrow) and neointima formation (double arrow). In case of treatment failure with HPS (C), the stent struts were covered with a thin, discontinuous neointima with leaks responsible for the residual aneurysm (partially shown, black asterisk). Successful occlusion of fusiform aneurysms by an FD (D) was associated with thick and complete neointimal coverage of the FD. (Movat staining, original magnification ×50.)

Fig 5.

Pathology of untreated, stented, and flow-diverted saccular aneurysms. The saccular aneurysm has an organized thrombus in its dome (white asterisk in A), with a thin wall with interruption of the elastic lamina at the neck (A, magnified view in B, black arrow). In case of treatment failure, the neck was wide open with a persistent aneurysmal cavity (black asterisk), which was only partially filled with unorganized thrombus (C), whereas in case of treatment success, the stent struts were covered with a thick and continuous neointima and the aneurysm cavity was filled with organized thrombus containing areas of hemosiderin (D) (Movat staining, original magnification ×50).