Histopathologic study for healing of aneurysm after flow diverter stenting in canine model

Abstract

Flow diverters (FDs) have been used widely for the treatment of intracranial aneurysms, showing good clinical results even in large and giant aneurysms. However, the exact healing mechanism associated with FDs remains poorly understood. The purpose of this study is to describe the healing process of aneurysms treated using a flow diverter by demonstrating the histopathologic progression in a canine aneurysm model. With institutional animal care and use committee approval, 24 side wall aneurysms were created in the common carotid artery of 8 dogs. All of 24 aneurysms were remained patently, and 21 of 24 aneurysms were used for FD deployment. Aneurysms were treated with two different flow diverters, 48- and 32-strand. Angiographic follow-up was performed immediately after placement of the device and at 4- and 12-weeks post treatment. At last follow-up, the aneurysm and the device-implanted parent artery were harvested. Angiographic findings revealed that the 48-strand flow diverter achieved a higher occlusion rate compared to the 32-strand flow diverter. Histopathologic examination of aneurysms with complete and near-complete occlusion at 4 weeks follow-up showed the development of intra-aneurysm thrombus formation in a laminating fashion, and neointimal thickening at the mid-segment of the aneurysm. The degree of thrombus formation and organization was variable, and the size of the aneurysmal sac also varied. At 12 weeks, examinations showed markedly shrunken aneurysmal sacs filled with organized connective tissue with a thin neointima. In aneurysms with incomplete occlusion at 4 weeks, aneurysmal sacs were most commonly filled with a multi-staged thrombus composed primarily of fresh blood clot with or without an empty space with neointimal thickening at the mid-segment of the aneurysm. At 12 weeks, examination showed a small amount of organized thrombus around the fringe neck and a large empty space with thick neointimal formation. Neointimal thickness was not significantly different between the two treatment groups or between the two follow-up periods. Among aneurysms showing the same angiographic outcomes at a specific follow-up period, various degrees and patterns of intra-aneurysmal thrombus formation with different sized aneurysm sacs were found. In conclusion, angiographic outcome could not represent a degree of aneurysm healing after FD deployment. Neointimal formation could occur along the struts of the FD independently of intra-aneurysmal thrombus formation. However, neointima formation could not solely lead to complete aneurysm healing. Intra-aneurysmal thrombus formation and organization seems to be an important factor for the complete occlusion of aneurysms treated using the FD.