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

Fluid-structure interaction simulation of the brachial artery undergoing flow-mediated dilation

Flow-mediated dilation (FMD) permits a non-invasive clinical assessment of endothelial dysfunction, a key indication of early atherosclerosis and cardiovascular diseases. This has significant implications with paediatric patients. FMD necessitates the measurement of brachial artery dilation from transient hyperaemia following a period of temporary ischemic occlusion. In addition to arterial diameter changes, the wall shear stress, blood pressure, and wall stiffness vary transiently in FMD, making it a complex fluid-structure interaction (FSI) problem. This work seeks to model the haemodynamic mechanisms associated with FMD utilising the open- source OpenFOAM-extend library1. Prior studies have demonstrated the suitability of this library for cardiovascular simulations2. Two FSI solvers, based on strong and weak coupling, were implemented for comparison. Both solvers utilise a partitioned approach, where the fluid and structure are solved separately and the information in each domain is exchanged at the FSI interface for each timestep. This is achieved using a dynamic mesh solver based on a discretisation of Laplace’s equation. The fluid flow solution is based on the finite volume method (FVM) and the displacement of the solid domain is solved by a Lagrangian FVM solver. The artery wall was modelled as a straight tube with physiological values for the internal diameter, density, wall thickness, Young’s modulus, and Poisson’s ratio3. A Newtonian incompressible fluid was assumed with physiological density and viscosity4. The inlet velocity for the fluid domain is specified from an in-vivo hyperaemic condition5. The simulation results demonstrate an important variation in the diameter of the arterial vessel during FMD, while haemodynamic wall shear stress and pressure values are also ascertained. These preliminary results are useful for comparing the implementation of strong and weak FSI solvers and for correlating arterial wall displacement with the prescribed in-vivo inlet velocity. Future work will focus on FMD in idealised and patient-specific bifurcation models where ischemic occlusion will be prescribed for the distal branching arteries

Multi-parameter computational model of flow mediated dilation with fluid-structure interaction coupled with lumped parameter approaches

Flow-mediated dilation (FMD) is a valuable non-invasive clinical assessment of endothelial dysfunction, a key indicator of atherosclerosis. The progression of atherosclerosis from paediatric ages can lead to the manifestation of cardiovascular diseases (CVDs) in later life. Hence, early lesion detection in younger years using FMD will heavily support timely disease assessment and treatment. In FMD, the diameter of the brachial artery is measured ultrasonically before, during, and after the inflation of a cuff applied to the lower arm of a subject. The cuff is placed distal to the ultrasound probe to capture predominantly endothelium-dependent vasodilation [1].The process induces a period of reactive hyperaemia, causing the brachial artery to vasodilate, due to an increase in shear stress that results in release of nitric oxide. The brachial artery ‘speak dilation is used for calculating the percentage difference between peak and baseline diameter (FMD percentage).Modelling FMD computationally offers a non-invasive assessment of vascular health and haemodynamic parameters

Patient-specific computational haemodynamics associated with the surgical creation of an arteriovenous fistula

Despite arteriovenous fistulae (AVF) being the preferred vascular access for haemodialysis, high primary failure rates (30-70%) and low one-year patency rates (40-70%) hamper their use. Furthermore, AVF creation has been associated with haemodynamic changes causing maladaptive cardiac remodelling leading to cardiovascular (CV) complications. In this study, we present a new workflow for characterising the haemodynamic profile prior to and following surgical creation of a successful left radiocephalic AVF in a 20-year-old end-stage kidney disease patient. The reconstructed vasculature was generated using multiple ferumoxytol-enhanced magnetic resonance angiography (FeMRA) datasets. Computational fluid dynamics (CFD) simulations utilising a scale-resolving turbulence model were completed to investigate the changes in the proximal haemodynamics following AVF creation, in addition to the post-AVF juxta-anastomosis flow patterns, which is impractical to obtain in-vivo. Following AVF creation, a significant 2-3-fold increase in blood flow rate was induced downstream of the left subclavian artery. This was validated through comparison with post-AVF patient-specific phase-contrast data. Proximal to the anastomosis, the increased flow rate yielded an increase in time-averaged wall shear stress (WSS), which is a key marker of adaptive vascular remodelling. In the juxta-anastomosis region, the success of the AVF was discussed with respect to the National Kidney Foundation's vascular access guidelines, where the patient-specific AVF met the flow rate and geometry criterion. The AVF venous diameter exceeded 6mm and the venous flow rate surpassed 600mL/min. This workflow may potentially be significant clinically when applied to multi-patient cohorts, with population-wide patient-specific conclusions being ascertained for the haemodynamic assessment of AVFs and improved surgical planning

Patient-specific computational haemodynamics in the arteriovenous fistula and aorta of a chronic kidney disease cohort

End-stage renal disease (ESRD) patients require renal replacement therapy (RRT) for filtering wastes and excess fluids from blood, often due to kidney transplant waiting times. Haemodialysis, the most common RRT, requires a vascular access for an efficient and repeatable procedure. An arteriovenous fistula (AVF) is widely considered the ‘gold-standard’ vascular access. However, AVFs suffer from poor patency rates, and their non-maturation is a key issue in failing cases. Localised haemodynamics and flow patterns are hypothesised to be prevalent factors behind AVF success. In addition to this, the impact of AVF creation on other parts of the haemodynamic network requires further elucidation. For example, the presence of an AVF is known to increase cardiac load and alter resistances in the vascular network. CFD enables a robust investigation into haemodynamic metrics that are not easily measurable in-vivo, such as wall shear stress (WSS) and oscillatory shear index (OSI). CFD can therefore play a vital role in the pre-operative planning of AVFs, in addition to the postsurgical assessment. Despite the breadth of AVF research that has utilised CFD, there is still no clear consensus on the mechanisms of AVF failure that result in fistula re-intervention or abandonment. Neointimal hyperplasia, the gradual loss of luminal patency due to the thickening of the vascular wall, and inadequate outward remodelling, an insufficient increase in venous diameter and elasticity, are the two major mechanisms behind AVF failure. Considering the highly patient-specific nature of AVF, vascular access guidelines have proposed a patient-centred care approach for determining an AVF site and morphology. Evaluating the localised haemodynamics in such patient-specific anatomy requires the acquisition and segmentation of high-quality images, a traditional blocker in this research area due to the contraindicating nature of historic contrast agents in the ESRD community. In this research, high-quality images from ferumoxytol-enhanced magnetic resonance angiography (FeMRA) were segmented for a cohort of chronic kidney disease (CKD) patients. These segmentations were then subsequently used for three CFD investigations, which is the first time FeMRA and CFD have been coupled together. The principal aims of this research were to i) investigate the influence of a successful AVF on a patient’s proximal haemodynamics, ii) replicate haemodynamics within a cohort of patient-specific AVF vessels to examine the impact of several metrics on future outcomes, and iii) to examine the haemodynamic differences in the subclavian arteries between successful and unsuccessful AVF cases within a cohort. The novelty in this research is four-fold, i) the segmentation and dataset registration workflow used for generating a patient-specific model (from aorta to AVF), ii) the use of computational fluid dynamics (CFD) for investigating proximal haemodynamics to an AVF, iii) the use of ferumoxytol as the contrast agent for generating patient-specific 3D vasculature models for a set of juxta-anastomosis CFD simulations, and iv) aortic haemodynamic CFD investigations in an ESRD cohort with AVFs. The investigations of this research demonstrated that i) the changes in vascular resistances induced from the creation of the AVF were found to markedly increase the WSS in the proximal vasculature of a 19-year-old patient with a radiocephalic AVF (Chapter 3), ii) the influence of cross-sectional juxta-anastomosis vessel characteristics (notably the feeding artery curvature) are the most prominent factor in determining AVF future success (Chapter 4), and iii) the WSS in the subclavian artery of the arm used for the AVF is 3-4 times higher than the opposite subclavian artery (Chapter 5). Having demonstrated the feasibility of generating patient-specific anatomy (using FeMRA) for CFD analysis, the future possibilities of research area are greatly increased. It is proposed that segmenting the AVF of several more cohorts can contribute to a repository/library of reference AVF models with haemodynamic analysis. Additionally, segmentation of further cohorts can open the doors to statistical shape modelling (SSM). Completing the workflow within this research for multiple cohorts, or by implementing SSM for the generation of multiple patient-specific derived anatomies of successful and unsuccessful AVF anatomies, can improve pre-surgical planning, as the surgeon can have a library of prior AVF in-silico trials to refer to.End-stage renal disease (ESRD) patients require renal replacement therapy (RRT) for filtering wastes and excess fluids from blood, often due to kidney transplant waiting times. Haemodialysis, the most common RRT, requires a vascular access for an efficient and repeatable procedure. An arteriovenous fistula (AVF) is widely considered the ‘gold-standard’ vascular access. However, AVFs suffer from poor patency rates, and their non-maturation is a key issue in failing cases. Localised haemodynamics and flow patterns are hypothesised to be prevalent factors behind AVF success. In addition to this, the impact of AVF creation on other parts of the haemodynamic network requires further elucidation. For example, the presence of an AVF is known to increase cardiac load and alter resistances in the vascular network. CFD enables a robust investigation into haemodynamic metrics that are not easily measurable in-vivo, such as wall shear stress (WSS) and oscillatory shear index (OSI). CFD can therefore play a vital role in the pre-operative planning of AVFs, in addition to the postsurgical assessment. Despite the breadth of AVF research that has utilised CFD, there is still no clear consensus on the mechanisms of AVF failure that result in fistula re-intervention or abandonment. Neointimal hyperplasia, the gradual loss of luminal patency due to the thickening of the vascular wall, and inadequate outward remodelling, an insufficient increase in venous diameter and elasticity, are the two major mechanisms behind AVF failure. Considering the highly patient-specific nature of AVF, vascular access guidelines have proposed a patient-centred care approach for determining an AVF site and morphology. Evaluating the localised haemodynamics in such patient-specific anatomy requires the acquisition and segmentation of high-quality images, a traditional blocker in this research area due to the contraindicating nature of historic contrast agents in the ESRD community. In this research, high-quality images from ferumoxytol-enhanced magnetic resonance angiography (FeMRA) were segmented for a cohort of chronic kidney disease (CKD) patients. These segmentations were then subsequently used for three CFD investigations, which is the first time FeMRA and CFD have been coupled together. The principal aims of this research were to i) investigate the influence of a successful AVF on a patient’s proximal haemodynamics, ii) replicate haemodynamics within a cohort of patient-specific AVF vessels to examine the impact of several metrics on future outcomes, and iii) to examine the haemodynamic differences in the subclavian arteries between successful and unsuccessful AVF cases within a cohort. The novelty in this research is four-fold, i) the segmentation and dataset registration workflow used for generating a patient-specific model (from aorta to AVF), ii) the use of computational fluid dynamics (CFD) for investigating proximal haemodynamics to an AVF, iii) the use of ferumoxytol as the contrast agent for generating patient-specific 3D vasculature models for a set of juxta-anastomosis CFD simulations, and iv) aortic haemodynamic CFD investigations in an ESRD cohort with AVFs. The investigations of this research demonstrated that i) the changes in vascular resistances induced from the creation of the AVF were found to markedly increase the WSS in the proximal vasculature of a 19-year-old patient with a radiocephalic AVF (Chapter 3), ii) the influence of cross-sectional juxta-anastomosis vessel characteristics (notably the feeding artery curvature) are the most prominent factor in determining AVF future success (Chapter 4), and iii) the WSS in the subclavian artery of the arm used for the AVF is 3-4 times higher than the opposite subclavian artery (Chapter 5). Having demonstrated the feasibility of generating patient-specific anatomy (using FeMRA) for CFD analysis, the future possibilities of research area are greatly increased. It is proposed that segmenting the AVF of several more cohorts can contribute to a repository/library of reference AVF models with haemodynamic analysis. Additionally, segmentation of further cohorts can open the doors to statistical shape modelling (SSM). Completing the workflow within this research for multiple cohorts, or by implementing SSM for the generation of multiple patient-specific derived anatomies of successful and unsuccessful AVF anatomies, can improve pre-surgical planning, as the surgeon can have a library of prior AVF in-silico trials to refer to

Patient-specific computational haemodynamics associated with the surgical creation of an arteriovenous fistula

Despite arteriovenous fistulae (AVF) being the preferred vascular access for haemodialysis, high primary failure rates (30-70%) and low one-year patency rates (40-70%) hamper their use. Furthermore, AVF creation has been associated with haemodynamic changes causing maladaptive cardiac remodelling leading to cardiovascular (CV) complications. In this study, we present a new workflow for characterising the haemodynamic profile prior to and following surgical creation of a successful left radiocephalic AVF in a 20-year-old end-stage kidney disease patient. The reconstructed vasculature was generated using multiple ferumoxytol-enhanced magnetic resonance angiography (FeMRA) datasets. Computational fluid dynamics (CFD) simulations utilising a scale-resolving turbulence model were completed to investigate the changes in the proximal haemodynamics following AVF creation, in addition to the post-AVF juxta-anastomosis flow patterns, which is impractical to obtain in-vivo. Following AVF creation, a significant 2-3-fold increase in blood flow rate was induced downstream of the left subclavian artery. This was validated through comparison with post-AVF patient-specific phase-contrast data. Proximal to the anastomosis, the increased flow rate yielded an increase in time-averaged wall shear stress (WSS), which is a key marker of adaptive vascular remodelling. In the juxta-anastomosis region, the success of the AVF was discussed with respect to the National Kidney Foundation's vascular access guidelines, where the patient-specific AVF met the flow rate and geometry criterion. The AVF venous diameter exceeded 6mm and the venous flow rate surpassed 600mL/min. This workflow may potentially be significant clinically when applied to multi-patient cohorts, with population-wide patient-specific conclusions being ascertained for the haemodynamic assessment of AVFs and improved surgical planning