Abstract

Thrombosis is a condition closely related to cerebral aneurysms and controlled thrombosis is the main purpose of endovascular embolization treatment. The mechanisms governing thrombus initiation and evolution in cerebral aneurysms have not been fully elucidated and this presents challenges for interventional planning. Significant effort has been directed towards developing computational methods aimed at streamlining the interventional planning process for unruptured cerebral aneurysm treatment. Included in these methods are computational models of thrombus development following endovascular device placement. The main challenge with developing computational models for thrombosis in disease cases is that there exists a wide body of literature that addresses various aspects of the clotting process, but it may not be obvious what information is of direct consequence for what modeling purpose (e.g., for understanding the effect of endovascular therapies). The aim of this review is to present the information so it will be of benefit to the community attempting to model cerebral aneurysm thrombosis for interventional planning purposes, in a simplified yet appropriate manner. The paper begins by explaining current understanding of physiological coagulation and highlights the documented distinctions between the physiological process and cerebral aneurysm thrombosis. Clinical observations of thrombosis following endovascular device placement are then presented. This is followed by a section detailing the demands placed on computational models developed for interventional planning. Finally, existing computational models of thrombosis are presented. This last section begins with description and discussion of physiological computational clotting models, as they are of immense value in understanding how to construct a general computational model of clotting. This is then followed by a review of computational models of clotting in cerebral aneurysms, specifically. Even though some progress has been made towards computational predictions of thrombosis following device placement in cerebral aneurysms, many gaps still remain. Answering the key questions will require the combined efforts of the clinical, experimental and computational communities.

Highlights

  • The hemostatic process maintains the integrity of the circulatory system

  • This review aims to examine the various aspects of thrombus development in unruptured cerebral aneurysms, with particular focus on those that are of relevance to developing virtual interventions

  • Comparison of Different Approaches Employed in Developing Computational Models of Cerebral Aneurysm Thrombosis Thrombosis potential studies create a link between hemodynamic variables and thrombus development

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Summary

INTRODUCTION

The hemostatic process maintains the integrity of the circulatory system. Under physiological conditions, clotting occurs following injury to a blood vessel. The key differences between physiological clotting and thrombosis in cerebral aneurysms relate to initiation For both processes, tissue factor must initiate the series of clotting reactions that result in the formation of a fibrin mesh, the source of this tissue factor is thought to differ (Bugge et al, 1996; Carmeliet et al, 1996; Toomey et al, 1996; Hoffman, 2003, 2004; Hoffman et al, 2006; Mann, 2006; Furie and Furie, 2008; Morel et al, 2011). The hemodynamic environment must be well characterized as disturbances in flow have a significant impact on platelet activation and protein transport

INSIGHTS FROM CLINICAL OBSERVATIONS OF THROMBOSIS IN CEREBRAL ANEURYSMS
Coiling in Unruptured Aneurysms
Flow Diversion in Unruptured Aneurysms
Full occlusion with coils prevents rebleeding
Lowest complication rates observed in small aneurysms
General Physiological Models
Cerebral Aneurysm Thrombosis Models
Mody and King
Medical imaging
CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS
Full Text
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