Modeling Fibrin Accumulation on Flow-Diverting Devices for Intracranial Aneurysms

Abstract

The mechanisms leading to aneurysm occlusion after treatment with flow-diverting devices are not fully understood. Flow modification induces thrombus formation within the aneurysm cavity, but fibrin can simultaneously accumulate and cover the device scaffold, leading to further flow modification. However, the interplay and relative importance of these processes are not clearly understood. A computational model of fibrin accumulation and flow modification after flow diversion treatment of cerebral aneurysms has been developed under the guidance of in vitro experiments and observations. The model is based on the loose coupling of flow and transport-reaction equations that are solved separately by independent codes. Interaction or reactive terms account for thrombin production from prothrombin stimulated by thrombogenic metallic wires and inhibition by antithrombin as well as fibrin production from fibrinogen stimulated by thrombin and flow shear stress, and fibrin adhesion to device wires and already attached fibrin. The computational model was demonstrated and tested on idealized vessel and aneurysm geometries. The model was able to reproduce the salient features of fibrin accumulation after the deployment of flow-diverting devices in idealized in vitro models of cerebral aneurysms. Namely, fibrin production in regions of high shear stress, initial accumulation at the inflow zone, and progressive occlusion of the device and corresponding flow attenuation. The computational model linking flow dynamics to fibrin production, transport, and adhesion can be used to investigate and better understand the effects that lead to fibrin accumulation and the resulting aneurysm inflow reduction and intra-aneurysmal flow modulation.

Keywords: cerebral aneurysms; coupling; fibrin accumulation; flow diversion; thrombosis.

FIGURE 1

Simplified fibrin production and accumulation model. PT = prothrombin, AT = antithrombin, Th = thrombin, Fg = fibrinogen, Fn = fibrin (free), Fb = bounded fibrin.

FIGURE 2

Computational mesh adaptively refined around deployed FD device wires.

FIGURE 3

Fibrin accumulation on device cells with different pore sizes placed perpendicularly to the flow in a straight tube. From top to bottom: velocities on a horizontal cut plane, concentration of prothrombin on the cut plane, concentration of thrombin on the cut plane, and isosurfaces of bounded fibrin concentration. Results are presented at a final time of approximately 20 min.

FIGURE 4

Fibrin accumulation on FD device in the idealized 3D‐printed model. Top row, left to right: vascular model, implanted FD device, velocity field on cut‐plane, velocity isosurface (v = 2 cm/s). Middle row, left to right: accumulation of fibrin (blue isosurface) and corresponding flow modification at three different time points, and final fibrin accumulation at aneurysm neck. Bottom row, left to right: fibrin accumulated at the neck of experimental models at four different time points. Red arrows indicate flow direction.

FIGURE 5

Flow visualization before (left column) and after FD device implantation in the computational model (center column) of sidewall aneurysm. Right column: flow visualization in the experimental model at three instants of time ($t_1<t_2<t_3$) using a purple dye (yellow arrows indicate dye movement inside the aneurysm).

FIGURE 6

Visualization of progressive fibrin accumulation in glass model of stented sidewall aneurysm and a corresponding computational model showing isosurfaces of fibrin attached to the wires (orange) and corresponding flow modification. Red arrows point to white opaque regions corresponding to fibrin accumulation in the in vitro models and corresponding bounded fibrin isosurfaces in the computational model.