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Multiscale Cardiovascular Engineering

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Research

Multi-Scale Modelling of Atherosclerotic Plaque Using Combined CFD, FSI and Systems Biology Approaches

The modelling of Atherosclerosis, i.e, the chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low-density lipoproteins (plasma proteins that carry cholesterol and triglycerides) is a complex, multi-scale problem, that depends on environmental factors, genetics, flow patterns, etc.

Objective

Our objective is to gather understanding of the formation of atherosclerotic plaque and how the plaque is formed, by coupling a 3D flow-simulations and FSI simulations with complex mathematical (systems) biology models to describe the formation of plaque and its growth. It is expected that by producing a workflow of the inflammation response of the wall, this project could be used an exemplar pipeline to describe the inflammation response of tissue under different biochemical pathways and conditions.

This project is in collaboration with Mr. O. Agu (UCLH & Royal Free Hospital) and Dr. Ines Pineda Torra (Clinical Pharmacology, UCL)

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Understanding Neo-Intimal Hyperplasia in Vascular Grafts and the Dynamics of Arteriovenous Fistulae Using Patient-Specific Simulations

Computational models for the study of vascular diseases are being continuously developed as tools for doctors and researchers. These models are of particular interest because they are able to take into account a variety of aspects of the disease including biomechanical aspects. These models do not only aim at creating a tool for better understanding the diseases and their causes, but also to make predictions regarding more crucial aspects for patients such as the disease progression and response to surgical treatment. We are currently expanding our atherosclerosis model to describe two new applications: the development of neo-intima hyperplasia (NIH) (testing our model within a sub-population of patients that have had infra-inguinal by-pass surgery) and in order to understand why arteriovenous fistulae fail.

These projects are in collaboration with the University of Yale (Prof. A. Dardik), the Royal Infirmary of Leeds (Prof. Shervanthi Homer) and the Royal Free hospital (UCL)


Cardiovascular Modelling: Investigation of the Fundamental Mechanics in Aortic Dissections under Patient-Specific Conditions as a Tool for Vascular Clinicians 

We use our mathematical models to predict patient-specific treatment for example or to understand cardiovascular pathophysiology.  We have chosen a challenging application in Aortic dissections (AD), a condition in which the wall of the aorta tears and blood flows in between the vessel wall layers. The blood pools in this region forming a false lumen (FL). If the FL ruptures, the onset of symptoms are  rapid and, in many cases, mortality occurs before the patient reaches the hospital. AD is difficult to diagnose, as it is often asymptomatic until the situation becomes severe. AD occurs largely as a result of interactions between hydrodynamic forces and the vessel wall. Therefore, it is important to improve the understanding of the blood flow in aortic dissections under patient-specific conditions.

This project is in collaboration with UCLH (Mr. O. Agu).


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Structural Uncertainties in Multiscale Models

Here, it is proposed to explore the structural uncertainty of multiscale models, through a combination of computational techniques within a nested optimisation algorithm, leading to a final “compromise” (solution) model. This will be applied to a multiscale biological problem of atherosclerosis plaque formation in mice.  The objective is to provide a 'proof of concept' of this approach, based on the atherosclerosis model developed by the group.

This project is in collaboration with Dr. Ines Pineda Torra, UCL, Clinical Pharmacology.

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Multi-physics and Multi-Scale Model of the Left Ventricle & Generation of Arrhythmias

Modelling and simulation of the complex interactions between the heart, vasculature and the systemic response to the changing physiological environment make it inappropriate to consider components of the cardiovascular system in isolation. Therefore, cardiovascular models require a multidisciplinary vision, presenting a particular challenge in that they require both a multi-physics and multi-scale (both, in length and time) approach. As the facility to model the interaction of solid and fluid mechanics in the cardiovascular system has developed, the need for improved and interactive boundary conditions has arisen. A solution is to couple lumped parameter models of the boundary conditions with a finite element model of the part where detail and accuracy are needed. Our objective is to develop multi-physics and multi-scale models of the left ventricle to be used either by themselves or as boundary condition to 3D models (valves, stents, LVADs) taking into account biochemical reactions at the cellular level and electro-mechanical events in the heart. We hope to be able to generate arrhythmias with a physiological basis.  We validate these models using an ex-vivo platform from colleagues in the Netherlands.

This project is in collaboration with the University of Eindhoven (Dr. M. Rutten) and the Lifetec group.

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Assessment of Percutaneous Heart Valves 

Heart valve replacement by percutaneous implantation can eliminate some of the main risks associated with invasive surgery for adults who cannot withstand the stress of open-heart surgery and children for whom treatment is delayed to avoid multiple highly invasive operations. This project will assess percutaneous valve devices suitable for both the pulmonary and aortic positions. The design of these devices will be analysed using computer modelling to predict mechanical performance in the short/long term and to help the cardiologists in the selection of the best prosthesis for specific patient anatomies. In addition, the aortic device fluid-dynamics will be studied to assess coronary perfusion. The hydrodynamic performance and durability of the valved devices will be assessed by in-vitro testing, according to current regulations and novel tests that may account for more realistic boundary conditions.

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Modelling and Simulation of Mitral Valve Dynamics for Patient Specific Treatment

The simulation of the physiological function and operational mechanisms of the cardiovascular system has a fundamental role in the understanding of its malfunctioning, as well as the development and assessment of improved therapies. This research is aimed at addressing multiscale and multiphysics modelling of the left ventricle, focussing on the dynamic interaction of the blood with the different structures of the heart, in particular the mitral valve. By using patient specific 3D finite element models of the left ventricle and mitral valve, which couple the non-linear deformation of the structures in response to physiological flows, we hope to yield more information on the state of ventricular haemodynamics and corresponding mitral leaflet dynamics in both normal and diseased states.

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