In Vitro Evaluation of Intra-Aneurysmal,Flow-Diverter-Induced Thrombus Formation: A Feasibility Study

BACKGROUND AND PURPOSE:Intracranial aneurysm treatment by flow diverters aims at triggering intra-aneurysmal thrombosis. By combining in vitro blood experiments with particle imaging velocimetry measurements, we investigated the time-resolved thrombus formation triggered by flow diverters.MATERIALS AND METHODS:Two test setups were built, 1 for particle imaging velocimetry and 1 for blood experiments, both generating the same pulsatile flow and including a silicone aneurysm model. Tests without flow diverters and with 2 different flow-diverter sizes (diameter: 4.5 and 4.0 mm) were performed. In the blood experiments, the intra-aneurysmal flow was monitored by using Doppler sonography. The experiments were stopped at 3 different changes of the spatial extent of the signal.RESULTS:No thrombus was detected in the aneurysm model without the flow diverter. Otherwise, thrombi were observed in all aneurysm models with flow diverters. The thrombi grew from the proximal side of the aneurysm neck with fibrin threads connected to the flow diverter and extending across the aneurysm. The thrombus resulting from the 4.0-mm flow diverter grew along the aneurysm wall as a solid and organized thrombus, which correlates with the slower velocities near the wall detected by particle imaging velocimetry. The thrombus that evolved by using the 4.5-mm flow diverter showed no identifiable growing direction. The entire thrombus presumably resulted from stagnation of blood and correlates with the central vortex detected by particle imaging velocimetry.CONCLUSIONS:We showed the feasibility of in vitro investigation of time-resolved thrombus formation in the presence of flow diverters.

Intracranial aneurysm treatment by flow diverters (FDs) aims at blood clotting in the aneurysm, triggered by the reduction or elimination of intra-aneurysmal blood flow. This therapeutic approach offers an alternative treatment for larger wide-neck aneurysms, in which coil embolization is associated with high recurrence.^1,2 Otherwise, a longer delay to complete intra-aneurysmal thrombosis and documented cases of postprocedural bleeding^3–5 suggest that the FD-driven mechanism of thrombus formation is considerably different from that using coils. In previous studies, it has been hypothesized that aneurysm rupture occurring in patients after treatment with FDs is a consequence of uncontrolled flow-driven clot formation resulting in thrombus-associated autolysis⁴ or mural destabilization of the aneurysm wall due to thrombus evolution.⁶The influence of FDs on hemodynamic properties was investigated in several in vitro experiments by particle imaging velocimetry (PIV). Especially, the influence of the geometry of the aneurysm,^7,8 the stent porosity,^7,9–12 the number of stents, and the stent material^8,13 on intra-aneurysmal velocity fields was extensively studied. All investigations were performed with water-glycerol mixtures as a blood analog fluid. The use of a transparent fluid is inevitable because PIV is an optical method, but it forestalls the possibility of investigate clotting effects. Therefore, because the thrombus-growing process influences the flow behavior, PIV investigations only represent the flow conditions directly after the insertion of FDs.The goal of our study was the in vitro investigation of time-resolved formation of thrombi triggered by FDs. Although biologic mechanisms, triggered by the aneurysm wall, are not depicted in the new in vitro model, the location and shape of thrombus during the forming and growing process, as well as the composition of the thrombus, were investigated for 2 different FD configurations. Moreover, we correlated the results with PIV measurements.