Thrombin-Fibrinogen In Vitro Flow Model of Thrombus Growth in Cerebral Aneurysms

Abstract

Cerebral aneurysms are balloon-like structures that develop on weakened areas of cerebral artery walls, with a significant risk of rupture. Thrombi formation is closely associated with cerebral aneurysms and has been observed both before and after intervention, leading to a wide variability of outcomes in patients with the condition. The attempt to manage the outcomes has led to the development of various computational models of cerebral aneurysm thrombosis. In the current study, we developed a simplified thrombin-fibrinogen flow system, based on commercially available purified human-derived plasma proteins, which enables thrombus growth and tracking in an idealized cerebral aneurysm geometry. A three-dimensional printed geometry of an idealized cerebral aneurysm and parent vessel configuration was developed. An unexpected outcome was that this phantom-based flow model allowed us to track clot growth over a period of time, by using optical imaging to record the progression of the growing clot into the flow field. Image processing techniques were subsequently used to extract important quantitative metrics from the imaging dataset, such as end point intracranial thrombus volume. The model clearly demonstrates that clot formation, in cerebral aneurysms, is a complex interplay between mechanics and biochemistry. This system is beneficial for verifying computational models of cerebral aneurysm thrombosis, particularly those focusing on initial angiographic occlusion outcomes, and will also assist manufacturers in optimizing interventional device designs.

Keywords: cerebral aneurysms; in vitro; thrombin–fibrinogen; thrombosis.

Fig. 1

(A) Flow setup illustrating the positioning of the different components relative to the flow phantom. (B) Design of the flow phantom which includes screw top to prevent leaks.

Fig. 2

Cloth growth over time. The zero time point marks the time at which the thrombin solution is injected into the aneurysm sac and comes into contact with the flowing fibrinogen solution. The red arrow at 0 second indicates the direction of fibrinogen flow.

Fig. 3

The estimated clot area from the two-dimensional images. The clot is seen to increase steadily in area over time.