Computational modelling of clot development in patient‐specific cerebral aneurysm cases

Abstract

Essentials• Clotting in cerebral aneurysms is a process that can either stabilize the aneurysm or lead to rupture.• A patient-specific computational model capable of predicting cerebral aneurysm thrombosis is presented.• The different clotting outcomes highlight the importance of personalization of treatment.• Once validated, the model can be used to tailor treatment and to clarify clotting processes in aneurysms.Summary. Background: In cerebral aneurysms, clotting can either stabilize the aneurysm sac via aneurysm occlusion, or it can have a detrimental effect by giving rise to embolic occlusion. Objective: The work presented in this study details the development of an in silico model that combines all the salient, clinically relevant features of cerebral aneurysm clotting. A comprehensive computational model of clotting that accounts for biochemical complexity coupled with three-dimensional hemodynamics in image-derived patient aneurysms and in the presence of virtually implanted interventional devices is presented. Methods: The model is developed and presented in two stages. First, a two-dimensional computational model of clotting is presented for an idealized geometry. This enables verification of the methods with existing, physiological data before the pathological state is considered.This model is used to compare the results predicted by two different underlying biochemical cascades. The twodimensional model is then extended to image-derived, three-dimensional aneurysmal topologies by incorporating level set methods, demonstrating the potential use of this model. Results and conclusion: As a proof of concept, comparisons are then made between treated and untreated aneurysms. The prediction of different clotting outcomes for different patients demonstrates that with further development, refinement and validation, this methodology could be used for patient-specific interventional planning.

Relative Roles of Mechanics and Biochemistry in the Initiation and Progression of Cerebral Aneurysm Thrombosis

“…This model consists of four main subsystems, namely flow, porosity and permeability, biochemistry, and level set, which were coupled to ensure that the results of the different systems had bearing on each other. The systems are described in the paragraphs that follow but greater detail can be found in the original paper [13].…”

“…Various computational models have been developed in effort to elucidate features of aneurysm thrombosis [9]- [13]. Even though they have been developed with different goals in mind, they all make a contribution to the effort of elucidating aneurysm thrombosis.…”

“…A distinction is made between these pathologies as it is thought that different mechanisms contribute to thrombus development in the two contexts. In this paper, we use a previously developed computational model to explore clotting patterns that emerge for different mechanical and biochemical inputs [13]. The study aims to examine how these different inputs lead to different outcomes, and which of those outcomes correlate with clot patterns observed in vivo.…”

Poiseuille Flow of a Non-Local Non-Newtonian Fluid with Wall Slip: A First Step in Modeling Cerebral Microaneurysms

“…A CFD model using an incompressible non-Newtonian constitutive law for the blood flowing with no-slip through a rigid-walled vessel was given in [8], while CFD models of incompressible Newtonian blood circulating with no-slip through vessels with deformable walls were presented in [12,13]. The role played by blood clotting in aneurysmal growth and rupture was studied in [15] using a complex atomistic-continuum model of hemodynamics and in [14] using mixture theory and diffusion-reaction equations for some blood proteins responsible for clotting formation and growth. A multi-particle collision dynamics approach was used in [16] to simulate blood flow through an axi-symmetric circular cylinder with slip, and the mechanical response of a deformable arterial wall to mechanical forces exerted on it by the exterior surrounding structures was studied in [17,18].…”

“…With a few exceptions, the blood is considered an incompressible Newtonian fluid in laminar flow through an artery of idealized geometry and having impermeable thin walls modeled as either rigid or viscoelastic solids. Recently, computer simulations of cerebral hemodynamics involving patient-specific geometries reconstructed from medical images and computational fluid dynamics (CFD) software have been performed, and some geometrical and hemodynamic parameters were proposed as biomarkers for aneurysmal rupture prediction [8][9][10][11][12][13][14][15]. A CFD model using an incompressible non-Newtonian constitutive law for the blood flowing with no-slip through a rigid-walled vessel was given in [8], while CFD models of incompressible Newtonian blood circulating with no-slip through vessels with deformable walls were presented in [12,13].…”