An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model

Abstract

Background and purpose: The potential for successful treatment of intracranial aneurysms by flow diversion is gradually being recognized in the clinical setting; however, the devices currently available (stents) are not designed for flow diversion. We evaluate the long-term response of an appropriately designed flow diversion device in producing thrombotic occlusion of experimental aneurysms.

Methods: Three different configurations of an original flow diversion device were implanted across thirty elastase-induced aneurysm models in rabbits. Ten animals per device configuration were followed-up for 3 weeks (n=3), 3 months (n=3), or 6 months (n=4), and tissue explanted postsacrifice was sent for histology. The temporal variation in angiographic contrast intensity within each aneurysm was fitted with a mathematical model to quantify the alteration in local hemodynamics caused by the implanted device. A predictive index, called the washout coefficient, was constructed to estimate long-term aneurysm occlusion probabilities immediately after treatment with any flow diversion device.

Results: The device with a porosity of 70% and pore density of 18 pores/mm(2) performed better at occluding aneurysms than devices with 70% porosity, 12 pores/mm(2) and 65% porosity, 14 pores/mm(2). A value of the washout coefficient less than 30 predicted greater than 97% angiographic aneurysm occlusion over a period of 6 months with a sensitivity of 73% and specificity of 82%.

Conclusions: The flow diversion devices effected successful and stable aneurysm occlusion. Pore density, rather than porosity, may be the critical factor modulating efficacy of such devices.

Figure 1

Image of one of the flow diversion device configurations (right) in comparison to a coronary stent (Wallstent, left).

Figure 2

Angiograms from one animal treated with device III showing the aneurysm (a) before device implantation, (b) immediately after device implantation, and (c) at 180 days follow-up.

Figure 3

(a) Mean percentage angiographic occlusion of the aneurysm at different follow-up time points for the 3 devices. (b) Mean thickness of the neointima formed on the luminal surface of the devices at different follow-up time points. * indicates significance (p<0.05) with respect to the other 2 devices at corresponding follow-up time; error bars represent one standard deviation.

Figure 4

(a) to (c): histological sections of the aneurysm from 3 animals treated with device III and followed-up at 21, 90 and 180 days post-treatment, respectively. Mature thrombus shows as a lighter shade as compared to acute thrombus with the staining method employed.

Figure 5

Scanning electron microscope images (a) Endothelial cells covering one of the device struts; the entire luminal surface of the devices was observed to have an endothelial lining; arrow shows flow direction in the parent artery (b) Patent vertebral artery ostium; arrow shows flow direction into the vertebral artery. The longitudinal axis of the vertebral is at an angle to the cut section of the subclavian. Both images of tissue obtained 180 days post-treatment.

Figure 6

(a) Aneurysmal washout curves for one case obtained before device III implantation (solid line) and immediately after device implantation (dashed line); after device implantation the amplitude of the curve is reduced to approximately 40% of the value before device implantation. Mathematical model-fits to the normalized washout curves obtained (b) pre-implantation and (c) immediately post-implantation quantify the increase in diffusive flow exchange produced by the device. Washout curves (dotted lines); model-fits (solid lines); convective components (dashed lines); diffusive components (dash-dot lines); after device implantation the amplitude and the time constant of the diffusive component are increased to 1.45 and 70 times the respective values before device implantation. (d) The receiver operating characteristic curve for the washout coefficient (W) data grouped based on angiographic aneurysm occlusion at follow-up (FU) of greater or less than 97%. Inset shows the contingency table based on the threshold value of 30.