Healing of Aneurysm after Treatment Using Flow Diverter Stent : Histopathological Study in Experimental Canine Carotid Side Wall Aneurysm

Abstract

Objective: Despite widespread use of flow diverters (FDs) to treat aneurysms, the exact healing mechanism associated with FDs remains poorly understood. We aim to describe the healing process of aneurysms treated using FDs by demonstrating the histopathologic progression in a canine aneurysm model.

Methods: Twenty-one side wall aneurysms were created in common carotid artery of eight dogs and treated with two different FDs. Angiographic follow-ups were done immediately after placement of the device, 4 weeks and 12 weeks. At last follow-up, the aneurysm and the device-implanted parent artery were harvested.

Results: Histopathologic findings of aneurysms at 4 weeks follow-up showed intra-aneurysm thrombus formation in laminating fashion, and neointimal thickening at the mid-segment of aneurysm. However, there are inhomogenous findings in aneurysms treated with the same type of FD showing same angiographic outcomes. At 12 weeks, aneurysms of complete and near-complete occlusion revealed markedly shrunken aneurysm filled with organized connective tissues with thin neointima. Aneurysms of incomplete occlusion at 12 weeks showed small amount of organized thrombus around fringe neck and large empty space with thick neointmal formation. Neointimal thickness and diameter stenosis was not significantly different between the groups of FD specification and follow-up period.

Conclusion: Intra-aneurysmal thrombus formation and organization seem to be an important factor for the complete occlusion of aneurysms treated using the FD. Neointimal formation could occur along the struts of the FD independently of intra-aneurysmal thrombus formation. However, neointimal formation could not solely lead to complete aneurysm healing.

Keywords: Aneurysm; Canine; Diversion; Flow; Histology; Stents.

Fig. 1.

Schematic diagram (A) and image (B) of the flow diverter configuration. This stent (B) contains 32 nitinol wires, 4 of which are equipped with platinum wire to enhance overall visibility. Mid segment of the stent has tight braiding distance.

Fig. 2.

A : Pre-procedural common carotid arteriogram shows a large, wide-necked side wall aneurysm (aneurysm 5) B : Four weeks FU angiograph of aneurysm 5 shows complete occlusion of aneurysm. C-E : Photomicrographs of aneurysm 5. Proximal (C), mid (D), and distal (E) segment of coronal sections shows multi-staged thrombus formation in concentrically laminated fashion (C-E : H-E stain, ×40). F : Midline longitudinal section of aneurysm 19 shows the thrombi revealed as irregular, ill-defined laminations which are mainly composed with organized thrombus (H-E stain, ×40). G : Midline longitudinal section of aneurysm 15 shows a significantly shrunken aneurysmal sac, and small area of organized thrombus and attenuated cellular matrix with neointimal hyperplasia around an aneurysmal neck (H-E stain, ×40). Neointimal hyperplasia was shown in the mid-segment of aneurysm, and it contained organized blood clot (arrowheads in D and F). FU : follow-up.

Fig. 3.

A : Four weeks FU angiograph of aneurysm 20 shows near complete occlusion of aneurysm (grade III). B : Midline longitudinal section of aneurysm 20 shows that aneurysmal sac was filled with laminated thrombus various stages of organization (H-E stain, ×40). C : Four weeks FU angiograph of aneurysm 18 shows near complete occlusion of aneurysm (grade III). D : Midline longitudinal section of aneurysm 18 shows that it was shrunken in its size, and fresh blood clot surrounded by organized thrombus was shown. Distant between stent struts was relatively wide at the segment proximity to the fresh blood clot (arrowheads in D) compared with other segments. E : Four weeks FU angiograph of aneurysm 9 shows incomplete occlusion of aneurysm (grade II). F and G : Photomicrographs of aneurysm 9. Mid (F) and distal (G) segment of coronal sections shows that the aneurysmal sac was filled with multi-staged thrombus mainly composed of fresh blood clot (arrows in G) with small empty space (arrows in F) (G and F : H-E stain, ×40). H : Four weeks FU angiograph of aneurysm 16 shows incomplete occlusion of aneurysm (grade II). I : Midline longitudinal section of Aneurysm 16 shows small amount of organized thrombus along the stent strut with intimal defect (arrow in I) (H-E stain, ×40). Small amount of fresh blood clot was show adjacent to the intimal defect with large empty space of the aneurysmal sac. Neointimal hyperplasia was shown in the midsegment of aneurysm, and it contained organized blood clot (arrowheads in F and I). FU : follow-up.

Fig. 4.

A : Gross inspection of completely occluded aneurysm 13 (grade IV). It is significantly shrunken in its size. B : Photomicrographs of mid-segment of coronal sections (aneurysm 13) (H-E stain, ×40). Aneurysmal sac was significantly shrunken, and histopathology shows small area of organized thrombus and attenuated cellular matrix with thin neointima. C : Native plane radiograph of aneurysm 14 obtained immediately after 12-week follow-up angiography. It shows small amount of contrast stagnation at the aneurysmal neck (grade III). D : Photomicrographs of aneurysm 14. Mid-segment of coronal section shows significantly shrunken aneurysmal sac, and small area of sharp, crescentic fresh blood clot and attenuated cellular matrix with thin neointima (H-E stain, ×40). E : Pre-procedural common carotid arteriogram shows a large, wide-necked side wall aneurysm (aneurysm 4). F : Twelve-weeks follow-up angiograph of aneurysm 4 shows incomplete occlusion of the aneurysm, and neointimal formation with intimal defect at the distal segment of aneurysmal neck. G and H : Photomicrographs of aneurysm 4. Proximal (G) and mid (H) segment of coronal sections shows empty sac with small amount of variably organized thrombus formation at the fringe neck formed between aneurysmal wall and stent struts with intimal hyperplasia at proximal segment of aneurysm (G and F : H-E stain, ×40).