Modelling the evolution of cerebral aneurysms: biomechanics, mechanobiology and multiscale modelling

Intracranial aneurysms (IAs) are abnormal dilatations of the cerebral vasculature. Computational modelling may shed light on the aetiology of the disease and lead to improved criteria to assist diagnostic decisions. We briefly review models of aneurysm evolution to date and present a novel fluid-solid-growth (FSG) framework for patient-specific modelling of IA evolution. We illustrate its application to 4 clinical cases depicting an IA. The section of arterial geometry containing the IA is removed and replaced with a cylindrical section: this represents an idealised section of healthy artery upon which IA evolution is simulated. The utilisation of patient-specific geometries enables G&R to be explicitly linked to physiologically realistic spatial distributions and magnitudes of haemodynamic stimuli. In this study, we investigate the hypothesis that elastin degradation is driven by locally low wall shear stress (WSS). In 3 out of 4 cases, the evolved model IA geometry is qualitatively similar to the corresponding in vivo IA geometry. This suggests some tentative support for the hypothesis that low WSS plays a role in the mechanobiology of IA evolution

The Role of Biofluid Mechanics in the Assessment of Clinical and Pathological Observations: Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28–30, 2008 Pasadena, California

Biofluid mechanics is increasingly applied in support of diagnosis and decision-making for treatment of clinical pathologies. Exploring the relationship between blood flow phenomena and pathophysiological observations is enhanced by continuing advances in the imaging modalities, measurement techniques, and capabilities of computational models. When combined with underlying physiological models, a powerful set of tools becomes available to address unmet clinical needs, predominantly in the direction of enhanced diagnosis, as well as assessment and prediction of treatment outcomes. This position paper presents an overview of current approaches and future developments along this theme that were discussed at the 5th International Biofluid Symposium and Workshop held at the California Institute of Technology in 2008. The introduction of novel mechanical biomarkers in device design and optimization, and applications in the characterization of more specific and focal conditions such as aneurysms, are at the center of attention. Further advances in integrative modeling, incorporating multiscale and multiphysics techniques are also discussed

Virtual Flow-T Stenting for Two Patient-Specific Bifurcation Aneurysms

The effective treatment of wide necked cerebral aneurysms located at vessel bifurcations (WNBAs) remains a significant challenge. Such aneurysm geometries have typically been approached with Y or T stenting configurations of stents and/or flow diverters, often with the addition of endovascular coils. In this study, two WNBAs were virtually treated by a novel T-stenting technique (Flow-T) with a number of braided stents and flow-diverter devices. Multiple possible device deployment configurations with varying device compression levels were tested, using fast-deployment algorithms, before a steady state computational hemodynamic simulation was conducted to examine the efficacy and performance of each scenario. The virtual fast deployment algorithm based on a linear and torsional spring analogy is used to accurately deploy nine stents in two WNBAs geometries. The devices expand from the distal to proximal side of the devices with respect to aneurysm sac. In the WNBAs modelled, all configurations of Flow-T device placement were shown to reduce factors linked with increased aneurysm rupture risk including aneurysm inflow jets and high aneurysm velocity, along with areas of flow impingement and elevated wall shear stress (WSS). The relative position of the flow-diverting device in the secondary daughter vessel in the Flow-T approach was found to have a negligible effect on overall effectiveness of the procedure in the two geometries considered. The level of interventionalist-applied compression in the braised stent that forms the other arm of the Flow-T approach was shown to impact the aneurysm inflow reduction and aneurysm flow pattern more substantially. In the Flow-T approach the relative position of the secondary daughter vessel flow-diverter device (the SVB) was found to have a negligible effect on inflow reduction, aneurysm flow pattern, or WSS distribution in both aneurysm geometries. This suggests that the device placement in this vessel may be of secondary importance. By contrast, substantially more variation in inflow reduction and aneurysm flow pattern was seen due to variations in braided stent (LVIS EVO or Baby Leo) compression at the aneurysm neck. As such we conclude that the success of a Flow-T procedure is primarily dictated by the level of compression that the interventionalist applies to the braided stent. Similar computationally predicted outcomes for both aneurysm geometries studied suggest that adjunct coiling approach taken in the clinical intervention of the second geometry may have been unnecessary for successful aneurysm isolation. Finally, the computational modelling framework proposed offers an effective planning platform for complex endovascular techniques, such as Flow-T, where the scope of device choice and combination is large and selecting the best strategy and device combination from several candidates is vital

Characterizing and Modeling Bone Formation during Mouse Calvarial Development

© 2019 American Physical Society. The newborn mammalian cranial vault consists of five flat bones that are joined together along their edges by soft fibrous tissues called sutures. Early fusion of these sutures leads to a medical condition known as craniosynostosis. The mechanobiology of normal and craniosynostotic skull growth is not well understood. In a series of previous studies, we characterized and modeled radial expansion of normal and craniosynostotic (Crouzon) mice. Here, we describe a new modeling algorithm to simulate bone formation at the sutures in normal and craniosynostotic mice. Our results demonstrate that our modeling approach is capable of predicting the observed ex vivo pattern of bone formation at the sutures in the aforementioned mice. The same approach can be used to model different calvarial reconstruction in children with craniosynostosis to assist in the management of this complex condition

Morphomechanical Innovation Drives Explosive Seed Dispersal

How mechanical and biological processes are coordinated across cells, tissues, and organs to produce complex traits is a key question in biology. Cardamine hirsuta, a relative of Arabidopsis thaliana, uses an explosive mechanism to disperse its seeds. We show that this trait evolved through morphomechanical innovations at different spatial scales. At the organ scale, tension within the fruit wall generates the elastic energy required for explosion. This tension is produced by differential contraction of fruit wall tissues through an active mechanism involving turgor pressure, cell geometry, and wall properties of the epidermis. Explosive release of this tension is controlled at the cellular scale by asymmetric lignin deposition within endocarp b cells-a striking pattern that is strictly associated with explosive pod shatter across the Brassicaceae plant family. By bridging these different scales, we present an integrated mechanism for explosive seed dispersal that links evolutionary novelty with complex trait innovation

On the Validation of a Multiple-Network Poroelastic Model Using Arterial Spin Labeling MRI Data

The Multiple-Network Poroelastic Theory (MPET) is a numerical model to characterize the transport of multiple fluid networks in the brain, which overcomes the problem of conducting separate analyses on individual fluid compartments and losing the interactions between tissue and fluids, in addition to the interaction between the different fluids themselves. In this paper, the blood perfusion results from MPET modeling are partially validated using cerebral blood flow (CBF) data obtained from arterial spin labeling (ASL) magnetic resonance imaging (MRI), which uses arterial blood water as an endogenous tracer to measure CBF. Two subjects—one healthy control and one patient with unilateral middle cerebral artery (MCA) stenosis are included in the validation test. The comparison shows several similarities between CBF data from ASL and blood perfusion results from MPET modeling, such as higher blood perfusion in the gray matter than in the white matter, higher perfusion in the periventricular region for both the healthy control and the patient, and asymmetric distribution of blood perfusion for the patient. Although the partial validation is mainly conducted in a qualitative way, it is one important step toward the full validation of the MPET model, which has the potential to be used as a testing bed for hypotheses and new theories in neuroscience research

Computational modelling of thrombotic processes and complex haemodynamics in cerebral aneurysms

A clot in a cerebral aneurysm can either accelerate the road to rupture, through inflammatory processes and furthering vascular wall degradation, or stabilise the situation by occluding the aneurysm, and thus prevent rupture. A three-dimensional computational model of clotting in patient-derived cerebral aneurysm geometries is presented. The model accounts for the biochemical reactions that make up the clotting process, for realistic three-dimensional haemodynamics in image-derived vasculature representations and for the growing clot’s interaction with and impact on the flow field. The flow is accounted for by the Navier Stokes equations and the transport equation describes the changes in biochemical species concentrations. Level Set methods are used to track the surface of the growing clot in the three-dimensional geometries studied. The influence of the thrombosed region on the haemodynamics is accounted for by modifying the local porosity and permeability, to reflect the fibrous and permeable nature of the clot. The model is first developed, examined and parameterised for a physiological model of clotting in two dimensions and is then extended and demonstrated for the pathological case in three dimensions. The framework developed is used to examine various aspects of clotting. The two-dimensional model is used to investigate the effects of critical thrombin concentration, tissue factor and the underlying biochemical cascade. The critical thrombin concentration at which coagulation transitions from the initiation to the propagation phase was found to be [TH] = 1 – 10nM. The inclusion of blood-borne tissue factor was found to reflect a more realistic thrombin production curve and an increase in initial tissue factor concentration led to a decrease in thrombin production lag time. The different underlying biochemical cascades produce similar results. The model is then extended to three dimensions and is used to investigate clot propagation and initiation in patient-derived aneurysms. The propagation velocity is linked to mechanical factors and biochemical species concentrations. An inverse relationship between strain rate and propagation velocity showed realistic clot growth. Realistic growth was also observed for a direct relationship with thrombin concentration and this seemed to be the most suitable approximation. The ways in which tissue factor, strain rate threshold and location of endothelial damage affect initiation are also examined. A strain rate of 500s-1 was found to be the highest strain rate at which fibrin controlled clot initiation took place. Above that value, no clotting was observed. The location of endothelial damage affected clot growth as evidenced by the reproduction of the clots observed under Lawton’s classification scheme. The three-dimensional model is then applied to patient-derived geometries and is used to examine the efficacy of flow diverter treatment. For a given geometry, clot growth is predicted for the case with and without a flow diverter. In some cases, clotting is a positive outcome while in other cases, the clot occludes the parent vessel. The unique contribution of this thesis is the combination of computational fluid dynamics, biochemistry and Level Set methods in complex, realistic, three-dimensional aneurysm geometries for clot prediction. The impact of the clot on the flow field is modelled by altering the porosity and permeability values of the clot region