Computational haemodynamics in arterial geometries in relation to obesity-induced cardiovascular diseases

Childhood and adolescent obesity, primarily a dietary disease, has become a major challenge of the modern society. Obesity is known to accelerate endothelial dysfunction, one of the key biological indicators of lesions of atherosclerosis that underlie most cardiovascular diseases. Early vascular changes can be clinically assessed with measurements of the aortic and carotid intima-media thickness (IMT), and flow-mediated dilatation (FMD) of the brachial, radial, femoral, or popliteal artery, induced by transient hyperaemia. The haemodynamic environment in high-risk patients is likely to be altered in a way that has not yet been clearly understood. This work will discuss the design and mesh generation challenges of idealised and anatomically-realistic vascular geometries, with the use of the ANSA® pre-processor (BETA CAE Systems SA), for the assessment of early signs of cardiovascular diseases in relation to obese children and adolescents. It will also present arterial models that attempt to clarify some of the flow-related mechanisms that are believed to contribute to early vascular changes. Numerical simulations of the time-dependent, incompressible Navier-Stokes equations will be presented utilising a high-fidelity finite volume solver in OpenFOAM®. The models help evaluate the haemodynamic shear stresses along the arterial walls and the possible location of early atherosclerotic lesions. Further work is ongoing on multi-scale computational modelling in patient-specific three-dimensional anatomies combining blood flow computations with macroscopic and microscopic features

Computational studies of blood flow at arterial branches in relation to the localisation of atherosclerosis

Atherosclerotic lesions are non-uniformly distributed at arterial bends and branch sites, suggesting an important role for haemodynamic factors, particularly wall shear stress (WSS), in their development. Using computational flow simulations in idealised and anatomically realistic models of aortic branches, this thesis investigates the role of haemodynamics in the localisation of atherosclerosis. The pattern of atherosclerotic lesions is different between species and ages. Such differences have been most completely documented for the origins of intercostal arteries within the descending thoracic aorta. The first part of the thesis deals with the analysis of wall shear stresses and flow field near the wall in the vicinity of model intercostal branch ostia using high-order spectral/hp element methods. An idealised model of an intercostal artery emerging perpendicularly from the thoracic aorta was developed, initially, to study effects of Reynolds number and flow division under steady flow conditions. Patterns of flow and WSS were strikingly dependent on these haemodynamic parameters. Incorporation of more realistic geometrical features had only minor effects. The WSS distribution in an anatomically correct geometry of a pair of intercostal arteries resembled in character the pattern seen in the idealised geometry. Under unsteady and non-reversing flow conditions, the effect of pulsatility was small. However, significantly different patterns were generated for reversing aortic near-wall flow and reversing side branch flow. The work was extended to study the wall shear stress distribution within the aortic arch and proximal branches of mice, in comparison to that of men. Mice are increasingly used as models to study atherosclerosis and it has been shown that, in knockout mice lacking the low density lipoprotein receptor and apolipoprotein E, lesions develop in vivo at the proximal wall of the entrance to the brachiocephalic artery. Three aortic arch geometries from wild-type mice were reconstructed from MRI images using in-house and commercial software, and the WSS distribution was calculated under steady flow conditions to establish the mouse haemodynamic environment and mouse-to-mouse variability. Approximated human aortic arch geometries were further considered to enable comparison of the flow and WSS fields with that of mice. The haemodynamic environment of the aortic arch varied between the two species. The overall distribution of wall shear stress was more heterogeneous in the human aortic arch than in the mouse arch, although some features were similar. Intraspecies differences in mice were small and influenced primarily by the detailed anatomical geometry and the Reynolds number. A number of simplifications were made in the above flow analyses, and clearly, relaxing these assumptions would increase complexity. Nonetheless, this thesis demonstrates the fundamental features of flow, which underlie the disparate patterns of WSS in different species and/or ages, for simplified cases, and the results are expected to be relevant to more complex ones. Aspects of the observed WSS patterns in the simplified model of intercostal artery correlate with, and may explain, some of the lesion patterns in human, rabbit and mouse aortas. WSS distributions in the aortic arch of wild-type mice associate with lesion locations seen in diseased mice.Open acces

Blood flow simulations in the human aortic arch in relation to obesity

The global obesity epidemic is worsening with 10% of the world’s population now classified as obese [1]. In 2015, obesity contributed to 4 million deaths globally, 41% of which were due to cardiovascular disease. The healthy human aorta has a complex anatomy often associated with disturbed flow dynamics, while in obese individuals structural and functional changes to the cardiovascular system lead to abnormal aortic function [2]. Such changes are also associated with coronary artery disease, hypertension, and diabetes; disorders which themselves are thought to be accelerated by obesity. In this study, we utilised computational fluid dynamic (CFD) methods to examine various haemodynamic parameters, namely blood flow velocity, blood pressure, and wall shear stress (WSS), in the aortic arch and proximal branches. Two idealised three-dimensional geometries of the human aortic arch, based on anatomically-correct data from two different patient groups [3], were created using the ANSA pre-processor (BETA CAE Systems). A mesh independence study was completed to determine the optimum number of elements for the geometries. CFD simulations were performed in the open-source library OpenFOAM®, with the material properties of the working fluid, blood, in accordance with current literature [4]. Preliminary results considered both steady and time-dependent (pulsatile) flow for the solution of the incompressible Newtonian Navier-Stokes equations. The initial focus of the flow analysis was on the distribution of wall shear stress. Flow patterns observed for both models showed regions of considerable flow disturbance. The results demonstrate low shear stresses at locations on the aortic wall which are known to be susceptible to the development of atherosclerotic plaques. Blood flow parameters are significantly affected by the local anatomy of the aortic arch, highlighting important differences between the two models. The future direction of this work is to improve the accuracy of the simulations by implementing more complex boundary conditions. The investigation will then be extended to patient-specific aortic models to confirm the results of this work

A computational fluid dynamic investigation of the obesity-altered hemodynamics in children and adolescents

Childhood obesity has become one of the major challenges of our century, taking epidemic proportions. Obesity, mainly a dietary disease, is known to advance endothelial dysfunction [1], an early sign of atherosclerotic lesions underling most cardiovascular diseases. Endothelial damage in high-risk paediatric patients can be clinically assessed with measurements of the aortic and carotid intima-media thickness (IMT), and flow-mediated dilatation (FMD) of the brachial, radial, and femoral arteries [2]. However, it is not yet clear how the haemodynamic environment is altered in this particular group of patients and which flow-related mechanisms contribute to early vascular changes. This work will discuss a computational model of an arterial conduit with compliant walls during FDM that attempts to clarify some of these aspects. Solutions to the time-dependent, incompressible Navier-Stokes equations are based on high-fidelity finite volume and hybrid Cartesian/immersed-boundary (HCIB) methods [3] that overcome several of the shortcomings of conventional computational fluid dynamic methods and provide increased spatial flow analysis. The codes have previously been validated and used extensively in various applications. Implementation of wall motion is particularly easy with HCIB methods, which are inherently capable of handling arbitrarily large body motions and allow for effective solutions of wall configuration. The model provides an evaluation of the haemodynamic shear stresses, a common indicator of early atherosclerotic lesion localisation. Future work will include multi-scale modelling that combines highresolution 3D blood flow computations, with macroscopic and microscopic features of the vascular environment. Further haemodynamic metrics, such as the time-averaged wall shear stress (TAWSS), the oscillatory shear index (OSI), and the transverse WSS will also be assessed, in conjunction with patient data

Computational mechanics in pediatric medicine : an overview

From foetuses, to newborns, to children and adolescents there is a large number of pediatric patients in need of computational strategies to improve the treatment of their conditions. In fact, the pediatric age is characterized by very rapid and sudden changes, which make it extremely difficult to test standardized paradigms of care. In turn, this makes pediatric treatments highly personalized, especially when it comes to surgeries and prosthetics. While on the one hand there is the difficulty of conducting wide clinical trials on large patient populations for each stage of growth and development, especially when it comes to rare congenital disease; on the other hand there is the need to treat these conditions as soon as possible, sometimes even in the womb, to ensure a good quality of life in these subjects. The growing use of computational mechanics as patient-specific predictive tools for adult treatments has spurred interest in engineers, researchers and physicians for the use of computational methods in predicting the outcome of highly personalized pediatric treatments, for which the need of prognostic tools is high and vital. The translation of established computational methods used in adults to pediatric patients has its own challenges, from the lack of high-quality images, as children are often spared CT-scans and X-rays, to the need of an accurate predictions in very rapid times. In this minisymposium we aim to explore the state of the art of this novel, interdisciplinary area of application of computational mechanics, continuing the success of a similar minisymposium in WCCM18. Therefore, it will include a review of the computational strategies applied to pediatric care: from fluid dynamic models applied to the identification of the best surgeries to correct congenital heart defect, to biomechanical computational approaches to assess growth in children, to numerical models of fetal development, to simulations of pediatric medical device treatments. The outcome of this minisymposium will be a productive gathering of minds, where experts from different areas of pediatric computational mechanics will gather together and exchange thoughts on strategies to overcome the challenges of this area of study and ideas to further the application of computational mechanics as a clinical tool for pediatric medicine

Computational hemodynamics research across the extremes of age

Hemodynamics problems often possess complex and multifaceted attributes that make real-world experimentation challenging. Computational modelling has been the gold standard for the assessment of such problems, highlighting key aspects of the underlying blood flow mechanisms in discrete conditions, while conducing to the development of novel prediction tools. In this talk, we will present three compelling cardiovascular topics that we address with the use of high-fidelity numerical approaches: a) multi-scale computational methods for obesity-altered hemodynamics in children and adolescents; b) blood flow dynamics in the surviving adult congenital heart patient; and c) simulation of cerebral aneurysm by flow diversion. The role of haemodynamic factors, particularly wall shear stress, and the use of state-of-the- art simulation methodologies will be presented. Cross-disciplinary perspectives between these topics and future efforts will be discussed

Towards a multi-scale computational tool for assessing the cardiovascular risk in obese children

Childhood obesity is considered one of the major challenges of our century, reaching epidemic rates. Although primarily a dietary disease, obesity is known to advance endothelial dysfunction [1], an early manifestation of atherosclerotic lesions that cause most cardiovascular diseases. Early vascular damage can be assessed clinically in various ways, for example with measurements of the aortic and carotid intima-media thickness (IMT), and flow-mediated dilatation (FMD) of the brachial, radial, and femoral arteries [2]. However, the altered haemodynamic environment in high-risk patients is not yet clearly understood and the flow-related mechanisms that contribute to early vascular changes have not been analysed. This work will discuss the design of a multi-scale computational tool for assessing such early signs in children and adolescents. It will also present a model of FMD that attempts to clarify some of these aspects. Solutions to the time-dependent, incompressible Navier-Stokes equations are based on high-fidelity finite volume and hybrid Cartesian/immersed-boundary (HCIB) methods [3] that overcome several of the shortcomings of conventional computational fluid dynamic methods and provide increased spatial flow analysis. The codes have previously been validated and used extensively in various applications. Implementation of wall motion is particularly easy with HCIB methods, which are inherently capable of handling arbitrarily large body motions and allow for effective solutions of wall configuration. The model provides an evaluation of the haemodynamic shear stresses, a common indicator of early atherosclerotic lesion localisation. Future work will include multi-scale modelling that combines high-resolution 3D blood flow computations, with macroscopic and microscopic features of the vascular environment. Further haemodynamic metrics, such as the time-averaged wall shear stress (TAWSS), the oscillatory shear index (OSI), and the transverse WSS will also be assessed, in conjunction with patient data

Numerical simulations of flow around intense appendage movements for aquatic propulsion

The flow dynamics around elongated slender geometries undergoing time- dependent intense motions, which apply to cases of appendage-based aquatic locomotion, is of considerable importance for understanding the energetics of these motions and for exploiting energy-efficient strategies to apply in novel propulsion designs. The difficulty in simulating such flows lies in the solution accuracy. The use of fixed-grid methods has been the gold standard for such flows, in which a moving (immersed) boundary is defined on a stationary domain; thus, these methods are capable of handling arbitrarily large motions and deformations and allow effective transient solutions of complex fluid problems. Within the immersed-boundary framework, we propose implementations for medium and extreme motions, ensuring stability and accuracy of transient motion results. The movements investigated are based on kinematic models extracted both from available three-dimensional motion reconstruction data of animal swimming and the literature. This study includes a series of specific geometries and motions, which entail parametric studies of performance and propulsive efficiency

A numerical approach for the assessment of obesity-induced vascular changes in children

Obesity in children and adolescents has taken epidemic proportions in recent years and has become one of the major challenges of the 21st century. Primarily a dietary disease, obesity is believed to accelerate the initiation and progression of endothelial dysfunction [1], one of the early biological markers for atherosclerotic lesions that underlie most cardiovascular diseases. Several markers have been proposed to help the clinical assessment of endothelial damage in high-risk paediatric patients. In obese children, arterial changes can painlessly be evaluated with measurements of the aortic and carotid intima-media thickness (IMT) and flowmediated dilatation (FMD) of the brachial, radial and femoral arteries [2]. Pulse wave analysis is additionally utilised to assess arterial stiffness, distensibility and compliance. This study observes childhood obesity under the magnifying lens of blood flow mechanics associated with obesity-induced vascular changes. The scope is to develop a safe and high-fidelity multi-scale computational tool for prognostic markers and predictive personalised care of obesity-related cardiovascular diseases, and transfer it into the paediatric reality. The current presentation will discuss a computational model of an arterial conduit during FDM

Fluid-structure interaction simulation of multiple bifurcations in arm under transient boundary conditions due to flow mediated dilation

Flow mediated dilation (FMD), a non-invasive clinical assessment of endothelial function, is a valuable indication of atherosclerosis. The haemodynamics associated with FMD are strongly influenced by the fluid-structure interaction (FSI)of the blood flow and arterial wall. In FMD, the diameter of the brachial artery is ultrasonically measured before, during and after a cuff being applied to the lower arm of the subject. The cuff is distal to the ultrasound probe to capture predominantly endothelium-dependent vasodilation. This cuff is inflated rapidly after establishing a baseline brachial artery diameter, the cuff remains inflated for 5 minutes and is then rapidly deflated. This process induces a period of reactive hyperaemia, resulting in the brachial artery to vasodilate due to the increased shear stress causing nitric oxide (NO) to be released. NO is a vasodilator. By assessing the peak diameter of the brachial artery, an FMD percentage can be calculated, this value reflects the subject’s endothelial function. FMD is calculated as a percentage between the peak arterial diameter and the baseline diameter of the brachial artery. The clinical application of the FMD test for establishing a subject’s endothelial function is very useful for paediatric patients that are predisposed to high cardiovascular(cv) risk. There are several risk factors that affect these patients, insulin resistance, sleep apnea, lack of physical exercise etc. Early detection of high cv risk using FMD will permit behavioural and or drug countermeasures to be incorporated in the patient’s lifestyle to prevent the accelerated development of atherosclerosis a high cv risk patient is likely to experience. Furthermore, patient specific modelling of the FMD test will remove the ethical issues of applying an inflated cuff to the lower arm of a paediatric patient. Additionally, computational modelling permits a wide and robust investigation into haemodynamic parameters that are not easily measurable in-vivo. These parameters, such as pulse wave velocity (PWV), oscillatory shear index (OSI) and wall shear stress (WSS)are valuable for assessing the development of atherosclerosis. Therefore, a numerical model using computational fluid dynamics (CFD)in STAR CCM+ has been generated for modelling the haemodynamics in the bifurcation of the brachial artery to the radial and ulnar arteries. Thus far, an idealised geometry has been utilised using geometry characteristics from a virtual database. The model has fluid-structure coupling due to the mapping between the CFD modelled fluid domain and the solid domain which is modelled using a finite volume solid stress model. The model employs transient boundary conditions in accordance with the cuff application under FMD. PWV and WSS in addition to wall displacement, velocity and pressure are presented