Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter

Ramanathan Kadirvel, Yong-Hong Ding, Daying Dai, Issa Rezek, Debra A Lewis, David F Kallmes, Ramanathan Kadirvel, Yong-Hong Ding, Daying Dai, Issa Rezek, Debra A Lewis, David F Kallmes

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.

© RSNA, 2013.

Figures

Figure 1:
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:
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:
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).

References

    1. Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A new endoluminal, flow-disrupting device for treatment of saccular aneurysms. Stroke 2007;38(8):2346–2352.
    1. Kallmes DF, Ding YH, Dai D, Kadirvel R, Lewis DA, Cloft HJ. A second-generation, endoluminal, flow-disrupting device for treatment of saccular aneurysms. AJNR Am J Neuroradiol 2009;30(6):1153–1158.
    1. Sadasivan C, Cesar L, Seong J, et al. . An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model. Stroke 2009;40(3):952–958.
    1. Cebral JR, Castro MA, Appanaboyina S, Putman CM, Millan D, Frangi AF. Efficient pipeline for image-based patient-specific analysis of cerebral aneurysm hemodynamics: technique and sensitivity. IEEE Trans Med Imaging 2005;24(4):457–467.
    1. Altes TA, Cloft HJ, Short JG, et al. . Creation of saccular aneurysms in the rabbit: a model suitable for testing endovascular devices. AJR Am J Roentgenol 2000;174(2):349–354.
    1. Hoefer IE, Grundmann S, Schirmer S, et al. . Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion. J Am Coll Cardiol 2005;46(6):994–1001.
    1. Schlitt A, Hauroeder B, Buerke M, et al. . Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model. Thromb Res 2002;107(1-2):39–43.
    1. Joner M, Nakazawa G, Finn AV, et al. . Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol 2008;52(5):333–342.
    1. Fischer S, Vajda Z, Aguilar Perez M, et al. . Pipeline embolization device (PED) for neurovascular reconstruction: initial experience in the treatment of 101 intracranial aneurysms and dissections. Neuroradiology 2012;54(4):369–382.
    1. Lubicz B, Collignon L, Raphaeli G, De Witte O. Pipeline flow-diverter stent for endovascular treatment of intracranial aneurysms: preliminary experience in 20 patients with 27 aneurysms. World Neurosurg 2011;76(1-2):114–119.
    1. Lubicz B, Collignon L, Raphaeli G, et al. . Flow-diverter stent for the endovascular treatment of intracranial aneurysms: a prospective study in 29 patients with 34 aneurysms. Stroke 2010;41(10):2247–2253.
    1. Wong GK, Kwan MC, Ng RY, Yu SC, Poon WS. Flow diverters for treatment of intracranial aneurysms: current status and ongoing clinical trials. J Clin Neurosci 2011;18(6):737–740.
    1. Kizilkilic O, Kocer N, Metaxas GE, Babic D, Homan R, Islak C. Utility of VasoCT in the treatment of intracranial aneurysm with flow-diverter stents. J Neurosurg 2012;117(1):45–49.
    1. Sadasivan C, Lieber BB, Cesar L, Miskolczi L, Seong J, Wakhloo AK. Angiographic assessment of the performance of flow divertors to treat cerebral aneurysms. Conf Proc IEEE Eng Med Biol Soc 2006;1:3210–3213.
    1. Wang K, Huang Q, Hong B, Li Z, Fang X, Liu J. Correlation of aneurysm occlusion with actual metal coverage at neck after implantation of flow-diverting stent in rabbit models. Neuroradiology 2012;54(6):607–613.
    1. Ishihara S, Mawad ME, Ogata K, et al. . Histopathologic findings in human cerebral aneurysms embolized with platinum coils: report of two cases and review of the literature. AJNR Am J Neuroradiol 2002;23(6):970–974.
    1. Bavinzski G, Talazoglu V, Killer M, et al. . Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg 1999;91(2):284–293.
    1. Ozawa T, Tamatani S, Koike T, et al. . Histological evaluation of endothelial reactions after endovascular coil embolization for intracranial aneurysm: clinical and experimental studies and review of the literature. Interv Neuroradiol 2003;9(Suppl 1):69–82.
    1. Frosen J, Marjamaa J, Myllarniemi M, et al. . Contribution of mural and bone marrow–derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model. Neurosurgery 2006;58(5):936–944; discussion 944.
    1. Li ZF, Fang XG, Yang PF, et al. . Endothelial progenitor cells contribute to neointima formation in rabbit elastase-induced aneurysm after flow diverter treatment. CNS Neurosci Ther 2013;19(5):352–357.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe