Organ Modelling and Simulation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting more than 6 million of Europeans. In the recent years new mapping technologies have been developed such as intracardiac mapping by basket catheters, body surface potential mapping by surface electrodes or estimated epicardial mapping by solving the inverse problem of electrocardiology. Together with these mapping technologies, signal processing techniques have been developed in order to identify the mechanism that maintains AF in each individual patient. However, due to the complexity of AF it is difficult to validate such techniques with real patient data.
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Imaging and computing technologies have advanced considerably in recent years leading to their increasing use in medical applications. Modern imaging methods allow clinicians to view the geometry of a patient’s vasculature, down to the level of individual vessels, allowing vascular malformations such as intracranial aneurysms to be located and examined. On a related front, the increasing availability and computational power of high performance computing (HPC) infrastructure now allows for detailed haemodynamic simulations to be executed [1]. Indeed, advanced software suites have already been developed for hemodynamic simulation from medical imaging, such as CRIMSON [2], including coupling to heart models [3]. The treatment of intracranial aneurysms is often performed under very short timescales. Our aim in this work is to use data which is already available and routinely collected in the process of interventions to treat patient aneurysms – such as rotational angiogram (RA) data – and combine this with high performance haemodynamics simulation codes to provide clinicians with real time visualisation of the predicted blood flow and associated wall shear stresses in the patient before and after the introduction of a flow diverting stent. We present here the fully integrated, automated pipeline we have developed to segment imaging data, localise aneurysms, simulate blood flow and provide real time visualisation to clinicians and some details of its current performance. Full Abstract

The INSIST consortium (www.insist-h2020.eu) set out to accelerate the advancement of stroke treatments by introducing in silico clinical trials which mitigate the need for resource-intensive experiments. The present work aims to contribute to INSIST by developing a cerebral circulation model that captures blood flow in the entire human brain. Progress in this field is complicated by the multi-scale nature of the flow, which stretches from small vessels with characteristic diameters of approximately 5 microns (capillaries) to large arteries with diameters of approximately 5 millimetres (e. g. internal carotid artery). Whereas it has become common practice to account for large arteries using one-dimensional network models, well-established methods are not available for a full description of the microcirculation. Therefore, this study focuses on the development of a cerebral microcirculation model and on bridging the gap between large arteries and the microcirculation. Full Abstract

High shear thrombosis happens on a thrombogenic surface (e.g. collagen) in a high shear environment and in presence of platelets and von Willebrand factor (vWF). In literature a discussion is going on between the need of an area with high shear [1] or an area with a high shear gradient [2]. However, the in vitro experiments used in these studies are performed in different flow chambers. In those flow chambers the specific flow fields are not the same. Currently, it is not known what specific flow characteristics cause high shear thrombosis. It is known that unfolding of the von Willebrand factor is regulated by elongational flow. However, this does not explain the formation of the platelet aggregates at the apex (high shear) or just behind the apex (high shear rate gradient), where vWF would contract instead of uncoil in the flow direction. However, note that the flow behaviour on the cellular level is hardly known and could provide additional insight [3]. Full Abstract

A clot, as observed in a stroke event is made of fibrin strands that are entangled, making a solid structure blocking partially or completely the blood flow in a brain artery. In addition to the fibrin network, the clots are made of other procoagulant factors such as platelets and von Willebrand Factor (vWF) as well as red blood cells (RBC).
Thrombosis is the result of the polymerization of the fibrinogen, transported by blood, into fibrin strands under the action of thrombin molecules. Thrombin is typically produced in case of body malfunction, such as injured endothelial cells, vessel walls exposed to low shear rate or hypoxia. In normal physiological conditions, the anti-thrombin that is naturally present in the blood can neutralize the thrombin and prevent from clot formation. Full Abstract

Neointimal hyperplasia (NIH) is a major obstacle to the long-term patency of peripheral vascular grafts. The disease has a complex aetiology which is influenced, among other phenomena, by mechanical forces such as shear stresses acting on the arterial wall.
The aim of this work is to use a multi-scale modelling approach to assess the impact of haemodynamic factors in NIH growth. We hypothesized that both low and oscillatory shear should be considered simultaneously when assessing the proclivity of a certain region in bypass grafts to develop NIH and we simulated NIH progression using a multi-scale computational framework that we previously developed, comparing our results to a patient specific clinical dataset (obtained with the patients’ informed consent for research and publication).
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Aortic dissection (AD) is a serious condition that occurs when a tear in the aortic wall allows blood to flow within the layers of the vessel. The optimal treatment of ‘uncomplicated’ acute/subacute Type-B aortic dissections (uABADs) continues to be debated. uABADs are commonly managed medically, but up to 50% of the cases will develop complications requiring invasive intervention [1].
AD is a highly patient-specific pathology in which morphological features have high impact on the haemodynamics. However, there is still a limited understanding of the fluid mechanics phenomena influencing AD clinical outcomes. Flow patterns, pressure, velocities and shear stresses are at the same time difficult to measure and extremely important features for this pathology.
Personalised computational fluid dynamics models (CFD) are being investigated as a tool to improve clinical outcome [2]. However, such models need to be rigorously validated in order to be translated to the clinic, and such validation procedures are currently lacking for AD. This scarcity of data may be supplemented using in silico and in vitro models, in which these parameters can be studied and compared for validation purposes.
In this work, a unique in vitro and in silico framework to perform personalised analyses of Type-B AD, informed by in vivo data, is presented.
Experimental flow rate and pressure waveforms, as well as detailed haemodynamics acquired via Particle Image Velocimetry (PIV), are compared at different locations against computational CFD results. Full Abstract

Every year about 735.000 Americans suffer from Coronary Artery Disease (CAD); one of the leading causes of death in the United States; therefore, diagnosis and treatment should be convenient and accurate with costs as low as possible. Currently, medium to high risk stable patients have been assessed based on invasive coronary angiography (ICA). In other words, ICA was the ‘gold standard’ to determine the appropriate treatment (pharmaceutical treatment, percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG)) for CAD by revealing the location and anatomy of the stenosis. This diagnostic method is based on the research of Gould et al., which demonstrates the relationship between the stenosis (lumen diameter) and ischemia (determined based on myocardial blood flow) during the hyperemic state (Gould et al., 1974). Despite the subjective visual interpretation of the clinician to interpret the ICA, the percentage stenosis defined by ICA is a decent indication for revascularization for single vessel stenosis. However, for diffuse coronary disease or multiple stenosis (Tonino et al., 2009), ICA is unreliable for the diagnosis, because hemodynamics are unpredictable based on the anatomy of the stenosis. This may result in unnecessary revascularization of patients. Full Abstract

The aim of this paper is to document recent methodological advancements that enable extreme scale simulation by HemeLB [1], our present lattice-Boltzmann (LB) based blood-flow solver. From pre-processing to simulation and finally post-processing, we demonstrate the entire work flow on SuperMUC-NG, a state-of-the-art high performance computing platform. Pre-processing involves the voxelisation of patient-specific geometries to form a large lattice consisting of up to tens of billions of sites. Our ultimate goal is to enable the simulation of virtual humans, or digital replicas, with HemeLB simulating the full arterial and venous trees and exchanging information with simulation tools responsible for capturing the behaviour of other organ systems. To create accurate digital patients, we rely on some of the recent advancements discussed here. Full Abstract

Physiologists interested in the body’s behaviour at exercise now recognize that the respiratory tract is not a limiting factor of endurance performance in healthy athletes. However, after several years of intense training, a majority of them develop various exercise-induced pathologies. The importance of the repetition of bronchial epithelium loss of integrity, consequent to a sustained high level of exercise ventilation, has been recently incriminated [1]. One physiological biomarker of the loss of epithelium integrity is the measurement of the concentration of club cells proteins 16kD (CC16) in urine or blood. An increase of this biomarker after exercise has been observed to be dependent on the intensity of exercise ventilation, leading to airway dehydration [1].
Interestingly, experimental [2] and modelling [3] works have shown that the bronchial epithelium and its mucus layer are a site of non-negligible evaporation during respiration. This evaporation (or condensation, especially during expiration [3]) is driven by a heat transfer between the air and the mucus layer, due to a temperature and humidity gradient at the air-tissue interface. Full Abstract

An ischemic stroke is caused by a blood clot (thrombus) in an intracranial artery that prevents the blood to supply the downstream tissues. The thrombus may originate from the heart, from atherosclerotic plaques, or from vessel wall dissections. It is a mass of platelets, fibrin, and other blood components, activated by a hemostasis mechanism, which may present different composition. Red thrombi, red blood cell (RBC) dominant, are usually generated where the blood flow is slow and the fibrin network entraps the RBCs, while white thrombi, fibrin dominant, are generated under high shear flow and inflammatory conditions. The clot composition affects strongly its mechanical properties [1].
The main diagnostic techniques used during the stroke investigation are the Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). In any case, detection of the location of the intracranial occlusion must be done in a fast and accurate way to ensure speedy treatment. Treatment of acute ischemic stroke is aimed at restoring blood flow in the affected cerebral arteries as fast as possible after onset. Time is crucial in stroke, 2 million neurons are lost every second without reperfusion. Full Abstract

Treatment of intracranial aneurysms with flow diverter stents (FDS) can lead to calibre changes of the jailed vessels in a subacute phase. The reason some branches remain unchanged and others are affected by narrowing or occlusion is unknown. This study investigates the influence of resistance to flow on FDS-induced haemodynamic modifications
in typical aneurysm locations in bifurcating arteries. Full Abstract

Computational modelling is becoming increasingly important towards the understanding, the diagnosis and the treatment of patients worldwide. It is a fact that modellers have been employing every last bit of information available to them to personalise and parameterise such models to increase their accuracy towards clinical applications. Data acquisition in the clinical scenario is many times hindered by monetary, ethical, time constraints, or simply the fact that there are some variables that are impossible to measure in-vivo. In this talk, we analyse the effect of trabeculae and papillary muscles on electrophysiology simulations of the male and female hearts. The aim is to characterise the effects of lack of anatomical resolution on the study of Ventricular Tachycardia. Furthermore, we analyse the role of gender phenotype on such simulations. Results show that anatomical detail and gender phenotype does really matter and provide different outcomes on computer simulation studies.

Predicting infarct volume is necessary to develop in silico trials for the treatment of acute ischaemic stroke. This requires modelling of blood flow across length scales incorporating three orders of magnitude, from the large arteries, to the arterioles, the pial surface vessels, to the penetrating vessels and the microcirculation. Blood flow in large vessels are typically modelled using lumped parameter or 1-D blood flow models, whereas the microcirculation is typically modelled as a porous medium[1]. However, the patient-specic geometry of large vessels is known, the features of the microcirculation are captured statistically. Therefore, there is an information gap between the large vessels and the microcirculation. Here, we present a method to couple blood flow in large blood vessels to cerebral tissue perfusion. A tissue perfusion model is also being developed but is outside the scope of this abstract1. For more details and derivations of the models, see [1, 2]. Full Abstract

The in-silico clinical trials for the treatment of acute ischemic stroke (INSIST) consortium is a multi-disciplinary, multi-sectorial undertaking aiming to advance the understanding and treatment of ischemic stroke through computational simulations and clinical trials. The work presented here is a part of this project which aims to model oxygen transport and metabolism in the entire human brain. This will form the backbone of the in-silico trials as this model, coupled with the multi-scale model of the blood flow in the human brain presented elsewhere in this conference1, will predict regions of hypoxia post-stroke, and hence will predict tissue death. This can then be validated against an available large database of stroke patients. Full Abstract

In recent years there have been significant developments in the application of computational workflows to enhance the clinical decision-making process. Many of these applications have been led by groups with an engineering focus and direct delivery of workflows within the clinical environment remains relatively uncommon. Due to the complex nature of patient specific anatomy and physiology, central to the effective development of state-of-the-art computational tools, workflows often require High Performance Computing (HPC) approaches and infrastructure to produce accurate, clinically relevant, output parameters. To improve clinical uptake of such technologies there is a need to provide direct access to such workflows to clinical end-users without exposing the complexity of the underlying HPC environment. This abstract describes the development of a software framework to deliver an existing HPC computational workflow Computed Tomography to Strength (CT2S), which provides quantitative metrics of bone strength based on CT images, directly to the clinical end-user. This provides the opportunity to initiate the request for computational analysis directly from the clinic, and returning an analysis report directly to the requesting clinician. Full Abstract

Spontaneous preterm birth (SPTB) is strongly associated with cervical funnelling. The condition is multifactorial and leads to global peri and neonatal mortality and morbidity [1,2], with the less developed countries being most affected due to a lack of management strategies. There exist a few treatment options for SPTB, including cervical cerclage [4], hormonal therapy using progesterone, and Arabin® cerclage pessary [3]. The Arabin® cerclage pessary has been widely used due to its low cost and ease of insertion. However, the mechanical interaction between the cervix and the pessary is not well understood [5]. Therefore, the aim of this study is to conduct preliminary investigation into: (a) the mechanical effect of the pessary on reducing cervix funelling, and (b) the effect of various pessary positions on supporting the cervix. Full Abstract