Vanessa Díaz-Zuccarini

Development of a patient-specific simulation tool to analyse aortic dissections: Assessment of mixed patient-specific flow and pressure boundary conditions

Aortic dissection has high morbidity and mortality rates and guidelines regarding surgical intervention are not clearly defined. The treatment of aortic dissection varies with each patient and detailed knowledge of haemodynamic and mechanical forces would be advantageous in the process of choosing a course of treatment. In this study, a patient-specific dissected aorta geometry is constructed from computed tomography scans. Dynamic boundary conditions are implemented by coupling a three element Windkessel model to the 3D domain at each outlet, in order to capture the essential behaviour of the downstream vasculature. The Windkessel model parameters are defined based on clinical data. The predicted minimum and maximum pressures are close to those measured invasively. Malperfusion is indicated and complex flow patterns are observed. Pressure, flow and wall shear stress distributions are analysed. The methodology presented here provides insight into the haemodynamics in a patient-specific dissected aorta and represents a development towards the use of CFD simulations as a diagnostic tool for aortic dissection.

Aortic dissection simulation models for clinical support: fluid-structure interaction vs. rigid wall models

BackgroundThe management and prognosis of aortic dissection (AD) is often challenging and the use of personalised computational models is being explored as a tool to improve clinical outcome. Including vessel wall motion in such simulations can provide more realistic and potentially accurate results, but requires significant additional computational resources, as well as expertise. With clinical translation as the final aim, trade-offs between complexity, speed and accuracy are inevitable. The present study explores whether modelling wall motion is worth the additional expense in the case of AD, by carrying out fluid-structure interaction (FSI) simulations based on a sample patient case.MethodsPatient-specific anatomical details were extracted from computed tomography images to provide the fluid domain, from which the vessel wall was extrapolated. Two-way fluid-structure interaction simulations were performed, with coupled Windkessel boundary conditions and hyperelastic wall properties. The blood was modelled using the Carreau-Yasuda viscosity model and turbulence was accounted for via a shear stress transport model. A simulation without wall motion (rigid wall) was carried out for comparison purposes.ResultsThe displacement of the vessel wall was comparable to reports from imaging studies in terms of intimal flap motion and contraction of the true lumen. Analysis of the haemodynamics around the proximal and distal false lumen in the FSI model showed complex flow structures caused by the expansion and contraction of the vessel wall. These flow patterns led to significantly different predictions of wall shear stress, particularly its oscillatory component, which were not captured by the rigid wall model.ConclusionsThrough comparison with imaging data, the results of the present study indicate that the fluid-structure interaction methodology employed herein is appropriate for simulations of aortic dissection. Regions of high wall shear stress were not significantly altered by the wall motion, however, certain collocated regions of low and oscillatory wall shear stress which may be critical for disease progression were only identified in the FSI simulation. We conclude that, if patient-tailored simulations of aortic dissection are to be used as an interventional planning tool, then the additional complexity, expertise and computational expense required to model wall motion is indeed justified.

Fluid-structure interaction study of the edge-to-edge repair technique on the mitral valve

The effect of functional mitral regurgitation has been investigated in an anatomically sized, fluid-structure interaction mitral valve model, where simulated correction has been performed by applying: (1) edge-to-edge repair with annuloplasty and (2) edge-to-edge repair only. Initially defined in an open unstressed/corrected configuration, fluid-structure interaction simulations of diastole have been performed in a rigid ventricular volume. Comparison of the maximum principal stresses (during diastole) in the normal and repaired models has shown that the magnitude of stress in the repaired scenarios is ~200% greater. The combined edge-to-edge and annuloplasty procedure was found to spread the induced stresses across the free margin of the leaflets, whereas without annuloplasty a localised stress concentration in the region of the suture was observed. Fluid flow downstream of the corrected configurations was able to achieve the same magnitude as in the normal case, although the flow rate was impaired. The maximum flow rate was found to be reduced by 44-50% with the peak flow rate shifted from the end of the diastole in the normal case to the start in the repaired cases.

Systemic modelling and computational physiology: The application of Bond Graph boundary conditions for 3D cardiovascular models

Abstract This paper presents an application of Bond Graphs in physiological modelling. In this work, a Bond Graph model is utilised as boundary condition for a detailed model of an idealized mitral valve. Applications of this type fit within the framework described by the “Virtual Physiological Human” initiative. This supports the integration of physical, mechanical and biochemical models encompassing a range of different length and time scales to obtain predictive models of the human body. Because 3D detailed modelling and simulation is computationally intensive, a 3D computational model of a whole biological system is, by today’s standards, impossible to achieve. Due to their unique multi-physics nature of internal coherence, Bond Graphs are particularly suited to biological applications and can be coupled to 3D models and lumped parameter models. A specific application in cardiovascular modelling is demonstrated by focusing on a specific example; a 3D model of the mitral valve coupled to a lumped parameter model of the left ventricle.

A Multiscale Model of Atherosclerotic Plaque Formation at Its Early Stage

A multiscale model of atherosclerotic plaque formation at its early stage has been developed in order to integrate the various phenomena leading to fatty streak formation. The different scales considered in this model are in both the spatial domain (from cellular to organism level) and the time domain (from seconds to months). The cellular level was considered by modeling the transport and chemical interactions of low-density lipoproteins (LDL) and other agents in a stenosed artery. This was linked to arterial thickening (organ level). Mean blood LDL level (organism level) was selected as one of the critical factors for atherosclerotic formation along with wall shear stress (WSS) exerted on the endothelium (the inner portion of the artery). It was observed that plaque location was dependent on WSS and that plaque size, number, and growth was dependent on mean blood LDL levels as well.

Virtual physiological human: training challenges

The virtual physiological human (VPH) initiative encompasses a wide range of activities, including structural and functional imaging, data mining, knowledge discovery tool and database development, biomedical modelling, simulation and visualization. The VPH community is developing from a multitude of relatively focused, but disparate, research endeavours into an integrated effort to bring together, develop and translate emerging technologies for application, from academia to industry and medicine. This process initially builds on the evolution of multi-disciplinary interactions and abilities, but addressing the challenges associated with the implementation of the VPH will require, in the very near future, a translation of quantitative changes into a new quality of highly trained multi-disciplinary personnel. Current strategies for undergraduate and on-the-job training may soon prove insufficient for this. The European Commission seventh framework VPH network of excellence is exploring this emerging need, and is developing a framework of novel training initiatives to address the predicted shortfall in suitably skilled VPH-aware professionals. This paper reports first steps in the implementation of a coherent VPH training portfolio.

Geometrical and Stress Analysis of Factors Associated With Stent Fracture After Melody Percutaneous Pulmonary Valve Implantation

Background—Patients treated with the Melody device (Medtronic) for percutaneous pulmonary valve implantation experience stent fractures in ≈25% of the cases. The aim of this study is to identify the risk factors associated with fracture using 3-dimensional (3D) analyses. Methods and Results—In situ 3D shape of the Melody stent was reconstructed from 42 patients using procedural biplane fluoroscopy images, after balloon inflation, at systole and diastole. Four geometric parameters at systole and their variation during balloon deflation and cardiac cycles were measured to describe the 3D strut, cell, section, and stent configuration. Furthermore, patient-specific computer simulations were set up to replicate the history of stent deformations for each patient. Maximum and minimum principal stresses resulting from these analyses were monitored during balloon deflation and cardiac cycle. Univariate logistic regression analyses of 21 geometric parameters and of 4 stress parameters respectively, identified the decreased stent circularity after balloon deflation (odds ratio 0.98; 95% confidence interval, 0.96–0.99; P=0.006) and large compressive stresses during balloon deflation (odds ratio, 0.98; 0.96–0.997; P=0.03), as associated with the risk of fracture. In a multivariable logistic regression model, the 2 covariates identified on univariate analysis (1 geometric and 1 stress) were found to be independently associated with the risk of fracture. The resultant statistical model correctly identified fracture/no fracture in 93% of patients. Conclusions—Changes in stent section shape after balloon deflation are important variables influencing fracture. This methodology could help design tailored follow-up for patients after percutaneous pulmonary valve implantation.

A multi-physics and multi-scale lumped parameter model of cardiac contraction of the left ventricle

In cardiovascular computational physiology the importance of understanding cardiac contraction as a multi-scale process is of paramount importance to understand causality across different scales. Within this study, a multi-scale and multi-physics model of the left ventricle that connects the process of cardiac excitation and contraction from the protein to the organ level is presented in a novel way. The model presented here includes the functional description of a cardiomyocyte (cellular scale), which explains the dynamic behaviour of the calcium concentration within the cell whilst an action potential develops. The cell domain is coupled to a domain that determines the kinetics of the sliding filament mechanism (protein level), which is at the basis of cardiac contraction. These processes are then linked to the generation of muscular force and from there to the generation of pressure inside the ventricle. This multi-scale model presents a coherent and unified way to describe cardiac contraction from the protein to the organ level.

Uncertainty assessment of imaging techniques for the 3D reconstruction of stent geometry

This paper presents a quantitative assessment of uncertainty for the 3D reconstruction of stents. This study investigates a CP stent (Numed, USA) used in congenital heart disease applications with a focus on the variance in measurements of stent geometry. The stent was mounted on a model of patient implantation site geometry, reconstructed from magnetic resonance images, and imaged using micro-computed tomography (CT), conventional CT, biplane fluoroscopy and optical stereo-photogrammetry. Image data were post-processed to retrieve the 3D stent geometry. Stent strut length, separation angle and cell asymmetry were derived and repeatability was assessed for each technique along with variation in relation to μCT data, assumed to represent the gold standard. The results demonstrate the performance of biplanar reconstruction methods is comparable with volumetric CT scans in evaluating 3D stent geometry. Uncertainty on the evaluation of strut length, separation angle and cell asymmetry using biplanar fluoroscopy is of the order ±0.2mm, 3° and 0.03, respectively. These results support the use of biplanar fluoroscopy for in vivo measurement of 3D stent geometry and provide quantitative assessment of uncertainty in the measurement of geometric parameters.

On the formalization of multi-scale and multi-science processes for integrative biology

The aim of this work is to introduce the general concept of ‘Bond Graph’ (BG) techniques applied in the context of multi-physics and multi-scale processes. BG modelling has a natural place in these developments. BGs are inherently coherent as the relationships defined between the ‘elements’ of the graph are strictly defined by causality rules and power (energy) conservation. BGs clearly show how power flows between components of the systems they represent. The ‘effort’ and ‘flow’ variables enable bidirectional information flow in the BG model. When the power level of a system is low, BGs degenerate into signal flow graphs in which information is mainly one-dimensional and power is minimal, i.e. they find a natural limitation when dealing with populations of individuals or purely kinetic models, as the concept of energy conservation in these systems is no longer relevant. The aim of this work is twofold: on the one hand, we will introduce the general concept of BG techniques applied in the context of multi-science and multi-scale models and, on the other hand, we will highlight some of the most promising features in the BG methodology by comparing with examples developed using well-established modelling techniques/software that could suggest developments or refinements to the current state-of-the-art tools, by providing a consistent framework from a structural and energetic point of view.