Mechanisms of occlusion and recanalization in canine carotid bifurcation aneurysms embolized with platinum coils: an alternative concept

Abstract

Background and purpose: Endovascular treatment of aneurysms may result in complete or incomplete occlusions or may be followed by recurrences. The goal of the present study was to better define pathologic features associated with so-called healing or recurrences after coiling and to propose an alternative concept to the currently accepted view.

Materials and methods: Experimental canine venous pouch aneurysms were created by using a T-type (group A, N = 29) or a Y-type constructed bifurcation (group B, N = 37) between the carotid arteries. Coil embolization was performed 2 weeks later; and angiography, immediately after and at 12 weeks. Angiographic results, neointima formation at the neck, endothelialization, and organization of thrombus were compared between groups by using qualitative scores and immunohistochemistry.

Results: Angiographic results at 3 months were significantly better in group A than in group B (P = .001). Macroscopic neointimal scores were also better (P = .012). Only 10/32 aneurysms with satisfactory results at angiography were completely sealed by neointima formation. Animals with residual or recurrent aneurysms had significantly worse neointimal scores than those with completely occluded ones (P = .0003). On histologic sections, the neointima was constantly present in "healed" and in recurrent aneurysms. This neointima was a multicellular layer of alpha-actin+ cells in a collagenous matrix, covered with a single layer of nitric oxide synthetase (NOS+) endothelial cells, whether it completely occluded the neck of the aneurysm or dived into the recurring or residual space between the aneurysm wall and the coil mass embedded in organizing thrombus.

Conclusion: Complete angiographic occlusions at 3 months can be associated with incomplete neointimal closure of the neck at pathology. Thrombus organization, endothelialization, and neointima formation can occur concurrently with recurrences.

Fig 1.

Schematic illustration of T- and Y-type carotid bifurcation aneurysm models.

Fig 2.

Angiographic and macroscopic results. Angiography (A, C, E) and macroscopic photographs (B, D, F) of prototypical cases of recurrence at 3 months and poor neointimal closure (A and B), complete occlusions at 3 months with good neointimal closure of the neck (C and D), and angiographic occlusion but with poor neointimal closure of the neck (E and F). Note that the coils have been removed in D.

Fig 3.

Macroscopic and pathologic findings of aneurysm with complete angiographic occlusion at 3 months after coil embolization. A, Photograph of aneurysmal neck en face. Note complete closure of the neck by a translucent layer of membrane tissue. B, Low-magnification overview of an axial aneurysm section showing a continuous layer of smooth muscle (SM) α-actin⁺ cells completely sealing the neck of the aneurysm. At higher magnification (C and D are magnifications of the inset c,d in B), closed corner (arrows in B and C) shows aligned SM α-actin⁺ cells covered by a single layer of NOS⁺ endothelial cells. E, The same neointimal layer is continuous, isolating the aneurysm from the circulation. F, SM α-actin immunostaining of atrophied aneurysmal wall. Sections are hematoxylin-counterstained (scale bar: 1000 μm for B; 200 μm for C–F; 40 μm for insets in C and D).

Fig 4.

Macroscopic and pathologic findings of recurring aneurysm 3 months after coil embolization. A, Macroscopic photograph showing incomplete neck closure. B, Low magnification of overview of axial aneurysm section revealing a recurring lesion extending from the corner of the neck to the body of the aneurysm (arrow). These crescentic spaces are lined by smooth muscle (SM) α–actin⁺ cells (C) and covered with NOS⁺ endothelial cells (D). E, Higher magnification showing the same layer of SM α-actin⁺ cells covered with NOS⁺ endothelial cells. F, Atrophy of the aneurysmal wall in the occluded zone. G, No atrophy of the aneurysmal wall in the recurring zone. Sections are hematoxylin-counterstained (scale bar: 1000 μm for B; 200 μm for C–G; 40 μm for insets in C and D).

Fig 5.

Common findings of occluded and recurrent aneurysms. Macroscopic views with coils protruding into the lumen vessel before (A) and after coil retrieval (B). Note that all coils are re-covered with neointima, which consists of smooth muscle (SM) cells (C) embedded in a collagenous matrix surrounded by a unique layer of NOS⁺ cells (D). Note polypoid filaments (pink arrows in A and E) observed at the neck of aneurysms, with a similar neointima organization (F). Sections are hematoxylin-counterstained (scale bar: 200 μm for C, D, and F; 40 μm for insets in C, D, and F).

Fig 6.

Vascularized connective tissues are similarly organized in occluded (A and C) and recurrent (B and D) aneurysm with smooth muscle (SM) α–actin⁺ cells, presumably myofibroblast (A and B) and NOS⁺ cells for neovascularization (C and D) (scale bar: 200 μm).

Fig 7.

Tissues infiltrating the core of the coils. Immunostaining of smooth muscle (SM) α–actin (A), of NOS (B), and Movat pentachrome stain (C) shows the same structure as the vascularized tissue inside the aneurysm (scale bar: 200 μm).

Fig 8.

Schematic illustration summarizing the differences between occlusion and recanalization.