Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter

Abstract

Purpose: To characterize the progression of healing across aneurysm necks following treatment with a flow diverter in a rabbit aneurysm model.

Materials and methods: With institutional animal care and use committee approval, saccular aneurysms were created in 20 rabbits and treated with flow diverters. On days 1, 3, and 7 and weeks 4 and 8 after implantation, the aneurysm and the device-implanted vessel were harvested. En face staining of the gross specimen was performed for endothelial cells, endothelial progenitor cells, smooth muscle cells, and inflammatory cells.

Results: The parent artery segments covered by the flow diverters were completely devoid of endothelial cells at 1 and 3 days but had completely reendothelialized by 7 days. At all time points, the struts along the patent portions of the aneurysm necks harbored scattered tissue islands composed exclusively of inflammatory cells. At 4 and 8 weeks, all samples contiguous with the tissue along the parent arteries had translucent tissue present along the occluded segments of the aneurysm neck. The vast majority of endothelial cells were contiguous with the parent artery and had smooth muscle cells underlying them. Endothelial progenitor cells were not observed along the neck of any aneurysm. Aneurysm closure was noted only when complete or nearly complete endothelialization over the device struts was present.

Conclusion: The initial event following flow diversion treatment is adherence of clusters of inflammatory cells across the aneurysm neck. Endothelialization is relatively delayed and derived exclusively from cells in the adjacent parent artery.

Figure 1:

A, DSA image obtained immediately before flow diverter implantation shows patent aneurysm cavity. B, DSA image obtained 8 weeks after flow diverter implantation shows substantial aneurysm remnant. C, Gross image of aneurysm neck, viewed from parent artery, shows multiple separate tissue islands (arrows) partially covering the neck. Two open pores (red and white stars) along the aneurysm periphery are shown on C and D. D, Immunostained confocal microscopic image of distal aspect of aneurysm neck–parent artery interface (CD31 stain; original magnification, ×20). Note confluent coverage with CD31-positive endothelial cells along more peripherally located struts (solid arrow) contiguous with parent artery, with well-demarcated interface between CD31-positive and CD31-negative cells (dashed arrow) covering more centrally located struts.

Figure 2:

A, DSA image obtained immediately before flow diverter implantation shows patent aneurysm cavity. B, DSA image obtained 8 weeks after flow diverter implantation shows near-complete occlusion. C, Gross image shows scattered tissue islands over neck (arrows). D, Photomicrograph of histopathologic slice through midportion of neck (hematoxylin-eosin stain; original magnification, ×100) shows neck remnant with endothelialized organized thrombus deep to neck. Tissue seen on C covering the neck was dislodged during processing, so no tissue is present over the neck on this slice. E, Immunostained confocal microscopic image of a tissue island noted in C (CD31 stain; original magnification, ×20). Note confluent coverage with CD31-positive endothelial cells along more peripherally located struts (solid arrow) in direct contiguity with parent artery, with a well-demarcated interface between CD31-positive and CD31-negative (dashed arrow) cells covering more centrally located struts. F, Confocal microscopic image of center of neck (CD31 stain; original magnification, ×20) shows, in foreground, CD31-negative cells attached to intersections of struts and corresponding to tissue islands on C and, in background, deep to struts, confluent endothelial cells as on D.

Figure 3:

A, DSA image obtained immediately before flow diverter implantation shows aneurysm cavity. B, DSA image obtained 8 weeks after flow diverter implantation shows occlusion of aneurysm. C, Gross image of aneurysm neck, viewed from parent artery, shows confluent tissue covering the neck (arrow). D, Dual immunofluorescence–stained confocal microscopic image of aneurysm neck (SMA and CD31 stains; original magnification, ×20) shows a confluent smooth muscle cell layer (red area, yellow arrow) deep to an incomplete layer of endothelial cells (green area, white arrow).