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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.

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.

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 Access

Recently, several therapies have emerged for Parkinson’s disease, a challenging neurodegenerative disorder. However, clinical translation is restricted, partially due to limitations in delivering therapeutics to the Central Nervous System (CNS)which cannot be reached by systemic administration. An alternative method, that bypasses the blood brain barrier and offers high-concentrated deposition in the diseased region, is intrastriatal delivery of a cell-loaded in situ forming collagen hydrogel. However, this strategy has disadvantages, including neuroimmune response and haemorrhage. To minimize these responses, an optimised medical device should be designed. Of main consideration is the volume dispensed and the needle dimensions. Current approaches use 18-20-Gaugediameter needles and multiple cranial penetrations. Additionally, fluid forces acting on cells may lead to cell disruption and death. This study aims to develop a novel device for the effective delivery of a cell-loaded in situ forming collagen hydrogel to the CNS. A simulation study on constricted channels representing the needle was performed to gain insight into the optimal needle diameter.

Pulmonary regurgitation is the most common, clinically-important, complication that affects an increasing population of adult patients with congenital heart disease, primarily with repaired tetralogy of Fallot. Without intervention, the condition can lead to abnormal dilatation of the right ventricle, arrhythmias, heart failure, or death. Pulmonary valve replacement (PVR) is a frequent reoperation, the clinical decision for which is currently relying on symptoms, including arrhythmias and measures of the right ventricular volume. However, there is no common consensus on the reliability of these criteria and further studies are needed for an accurate and timely assessment for PVR treatment. The overall objective of this work is to hemodynamically characterise the pulmonary bifurcation in adult patients with congenital heart disease, pre- and post-operatively, and help establish novel metrics for a more accurate assessment for PVR, contributing to better surgical planning. In this study, we present preliminary computational fluid dynamic results in simplified models of the pulmonary trunk and its branches, in order to investigate the effect of the bifurcation angle on the flow. Physiological vessel dimensions and boundary conditions were used, in both symmetric and asymmetric geometries, and blood flow was simulated by solving the incompressible Navier-Stokes equations. Increase of the branching angle altered the flow development within the bifurcation, and had evident effects on the flow separation downstream of the junction. Shear stresses on the wall connecting the two artery branches were found, for the first time, dependent also on the origin of each branch, having a greater effect on the left pulmonary artery. These results demonstrate the impact of geometry on velocity, pressure, and wall shear stresses in the pulmonary bifurcation and contribute to a better understanding of the underlying flow mechanisms. Future studies will involve 3D reconstruction of patient-specific models of the pulmonary bifurcation, obtained from MRI images of adult patients with repaired tetralogy of Fallot, that need or have undergone pulmonary valve replacement.

Neurodegenerative diseases, such as Parkinson’s disease, affect a large number of the erderly population and still remain untreated. In recent years, cell therapy has emerged as a promising therapeutic strategy. To increase cell viability, biomaterials are often used as scaffolds and facilitate cell deposition, through injection, to the site of interest. However, fluid forces acting on the cells during injection may lead to their disruption or death. This study aims to develop a novel device for the delivery of a cell-embedded, in situ forming, collagen hydrogel. A preliminary simulation study on constricted channels representing the syringe was performed to gain insight into the effect of needle diameter and syringe geometry. Straight needles emanating co-axially from syringes of various geometrieswere computationally modelled in the two-dimensional space, using OpenFOAM. The natural collagen solution was modelled as a continuum medium, without cells, and the flow was assumed incompressible, with non-Newtonian fluid constitutive behaviour. The effects of needle diameter and syringe geometry on velocity and shear stresses were examined. The results highlight the importance of geometric characteristics on the design of new cell delivery devices. If cells pass from the syringe barrel to the needle, the pressure drop and the increased velocity could damage them. This is more likely to occur using higher Gauge needles. Further analysis is required including simulations of cells during injection and analysis of their deformation.

Numerical simulations of flow surrounding a synthetic jet actuating device are presented. By modifying a dynamic mesh technique available in OpenFoam-a well-documented open-source solver for fluid dynamics, detailed computations of the sinusoidal motion of the synthetic jet diaphragm were possible. Numerical solutions were obtained by solving the two dimensional incompressible viscous N-S equations, with the use of a second order implicit time marching scheme and a central finite volume method for spatial discretization in both streamwise and crossflow directions. A systematic parametric study is reported here, in which the external Reynolds number, the diaphragm amplitude and frequency, and the slot dimensions are varied.

This review outlines some of the different scales involved in computationally modelling arterial networks. Starting at the largest O(1m) scale we highlight current activities in reduced modelling of the pulse waves. We then focus on the O(10-1m) scale and provide an example of how CFD can be applied to understand the role of mixing in small amplitude helical pipes at physiologically relevant flow conditions. Finally we motivate the interaction at O(10-3m) scale by considering how localised flow features are suggestive of different types of arterial disease patterns.

The delivery of a cell-embedded hydrogel to the striatum is a promising strategy for Parkinson’s disease. In this study, a computational model of the intrastriatal injection was used to analyze the delivery process.

The delivery of a cell-embedded hydrogel to the striatum is a promising strategy for Parkinson’s disease. In this study, a computational model of the intrastriatal injection was used to analyze the delivery process.