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

Ilunga J Tshimanga,Zahra Shaikh,Malebogo N Ngoepe,Etheresia Pretorius,Wei Hua Ho,Yiannis Ventikos

doi:10.1055/s-0041-1728790

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.

Highlights

Thrombosis and thrombi formation are closely associated with cerebral aneurysms, which are balloon-like structures on vessels of the brain resulting from a weakening of the vessel wall layers.[1,2,3]
The current hypothesis is that clots which partially occlude the aneurysm sac tend to lead to further vascular wall degradation, with increased risk of rupture, while those that fill the aneurysm sac contribute to stability.[3]
The results from the experiment clearly demonstrate that thrombus growth in an idealized cerebral aneurysm geometry is a complex interplay between biochemical and mechanical factors

Summary

Introduction

Thrombosis and thrombi formation are closely associated with cerebral aneurysms, which are balloon-like structures on vessels of the brain resulting from a weakening of the vessel wall layers.[1,2,3] Aneurysm risk can be assessed through imagebased screening on a population basis, of high-risk populations, clinical populations, or registries of patients. Thrombi have been observed both before and after intervention, leading to a wide variability of outcomes in patients with cerebral aneurysms. In an attempt to harness the benefits of constructive clotting, endovascular treatment of cerebral aneurysms was designed to aid complete occlusion of the aneurysm sac. This was achieved by placement of a high surface area device in the aneurysm sac (through endovascular coiling) or by redirecting flow to the parent vessel and out of the aneurysm sac (using flow diversion devices),[11,12] always with the aim to encourage development of a stable thrombus that completely occludes the aneurysm. The process is highly patient- and protocol-specific, and a solution that works for one individual may not necessarily be suitable across the board

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