Dissertations / Theses on the topic 'Cardiovascular fluid dynamic'

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.
En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.

This PhD thesis described the realization and development of a new experimental laboratory for cardiovascular studies. Three years later, the Healing Research Laboratory (HeR Lab) is an approved reality, located within the ICEA Dept. of the University of Padua. The present paper explores the different aspects that have been involved on its development, and the principal research fields that have been touched along the doctorate program. It is subdivided in four parts: a first overview of the aortic district linked to the insertion of prosthetic devices, from physiological and engineering points of views. After this, the experimental activities are widely discussed. The experimental research was focused on the design, realization, trial-tests and first optimization of a mechanical-hydraulic closed circuit (called pulse duplicator), for the study of fluid dynamics in the systemic circulation after the implantation of prosthetic devices. Innovative feature of the workbench is the presence of a compliant silicone phantom replica of a healthy aorta, that permits investigations of mechanics and flow dynamics characteristics of the district via an experimental approach. A third section is depicted to external experimental projects, developed within the division of Cardiac Surgery, dept. of cardiac, thoracic and vascular sciences, University of Padua Medical School, to investigate the haemodynamic performances of a total artificial heart (CardioWest TAH-t); and within the UCL Cardiovascular Engineering Laboratory (University College London, UK), to perform in vitro assessment of prosthetic cardiovascular devices performances (biological aortic valves). The last part focuses on a numerical study based on the design of a 2D mechanical model for a red blood cell, and the computation of deformation-damage effects on the shield, due to the shear stresses induced downstream of mechanical aortic valves. The possibility to made up an experimental laboratory, and the development of a new-born research group, give the chance to obtain strong expertise along these three years in the R&D field, giving the possibility to actually touch all the different faces of the research, from the funding recruitment to the physical workbench realization or prototype testing.
Nella presente tesi di Dottorato è descritta la realizzazione e lo sviluppo di un nuovo laboratorio sperimentale per studi di fluidodinamica cardiovascolare. Il laboratorio, denominato Healing Research Laboratory (HeR Lab), a tre anni dalla sua creazione, è una realtà di Dipartimento consolidata; presente nel dip. ICEA dell’Università degli Studi di Padova. Nel proseguo dell’elaborato vengono indagati gli aspetti che hanno partecipato allo sviluppo del laboratorio, ed i principali campi di ricerca che sono stati toccati lungo il percorso di dottorato. La tesi è strutturata in quattro parti principali: la prima fornisce una panoramica del distretto aortico, in relazione all’inserimento di device protesici, sia dal punto di vista fisiologico che ingegneristico. La seconda parte è incentrata nella descrizione approfondita della ricerca sperimentale. Si focalizza nella progettazione, realizzazione e messa punto di un circuito meccanico-idraulico (chiamato pulse duplicator), per lo studio della fluido dinamica nella circolazione sistemica, a seguito dell’impianto di dispositivi protesici. Parte innovativa è costituta dalla presenza di un prototipo siliconico compliante di radice aortica ottenuta da CT-scan di paziente, per lo studio delle caratteristiche meccaniche del vaso e dei campi fluidodinamici locali. La terza sezione è costituita da progetti sperimentali sviluppati in strutture esterne all’HeR Lab. Il primo presso la Cardiochirurgia, dipartimento di Scienze Cardiache, Toraciche e Vascolari della Università degli Studi di Padova, allo scopo di investigare le performance emodinamiche di un cuore artificiale totale (CardioWest TAH-t); la seconda come membro dell’UCL Cardiovascular Engineering Laboratory (University College London), con l’obiettivo di indagare le performance di valvole aortiche biologiche per via sperimentale. La quarta sezione descrive uno studio numerico basato sul design di un modello meccanico 2D del globulo rosso, e sul calcolo di deformazioni e danni subiti dalla membrana, dovuti agli sforzi tangenziali indotti dal flusso effluente da valvole aortiche meccaniche. Lo sviluppo del laboratorio e del nuovo gruppo di ricerca cardiovascolare ha permesso di incamerare ottime competenze nell’ambito della ricerca e progettazione, dando la possibilità di toccare diversi aspetti dello sviluppo, dalla ricerca fondi alla realizzazione fisica di prototipi o banchi sperimentali.

The diseases of cardiovascular system and the respiratory system have been the second and third killers causing deaths in Hong Kong. In this stressful civilized world, the prevalence and incidence of these diseases increased prominently which arouse our concern on the theories behind the pathological conditions. This report will focus on the biofluid mechanics in the large artery and in the upper airway. Thoracic aortic dissection, characterized by the tearing in the middle layer of vessel wall, is a catastrophic vascular disorder. The wall of the newly formed channel, the false lumen, is weakened and prone to aortic events. Endovascular repair is a minimally invasive technique for treating dissection patients. The biomechanical factors and the length of endograft were studied by computational fluid dynamics. Two geometrical factors showed a significant impact on the backflow in the false lumen. A larger false lumen and a larger distal tear size greatly affected the extent of thrombosis in the false lumen. It made the false lumen under a higher risk of vessel rupture. The computational prediction also demonstrated a more stable hemodynamic condition in the model with a longer endograft. These results provide important information for the clinicians to propose the surgical procedures and to improve the design of endografts. Airway obstruction is a common breathing disorder but it is always underdiagnosed. Obstructive sleep apnea (OSA) and different dentofacial deformities are two pathological conditions in which the patients have the abnormal sizes of airways. Computational fluid dynamic was employed in both conditions with patient–specific models. In the part of OSA, pre– and post–operative models were studied. The dimensions and flow resistance of the upper airway showed a significant improvement after mandibular distraction. The percentage of stenosis and the flow resistance was reduced by 27.3% and 40.7% respectively. For the patients in three facial skeletal deformity groups, the cross–sectional area and the flow resistance were compared. The patients with Class II deformity had the smallest retroglossal and retroplatal dimensions as well as the greatest flow resistance. The results confirmed the effectiveness of mandibular distraction and also provide valuable implications for the clinicians on the treatment planning, particularly for the Class II subjects.
published_or_final_version
Mechanical Engineering
Master
Master of Philosophy

Accurate and reliable modeling of cardiovascular hemodynamics has the potential to improve understanding of the localization and progression of heart diseases, which are currently the most common cause of death in Western countries. However, building a detailed, realistic model of human blood flow is a formidable mathematical and computational challenge. The simulation must combine the motion of the fluid, the intricate geometry of the blood vessels, continual changes in flow and pressure driven by the heartbeat, and the behavior of suspended bodies such as red blood cells. Such simulations can provide insight into factors like endothelial shear stress that act as triggers for the complex biomechanical events that can lead to atherosclerotic pathologies. Currently, it is not possible to measure endothelial shear stress in vivo, making these simulations a crucial component to understanding and potentially predicting the progression of cardiovascular disease. In this thesis, an approach for efficiently modeling the fluid movement coupled to the cell dynamics in real-patient geometries while accounting for the additional force from the expansion and contraction of the heart will be presented and examined.

First, a novel method to couple a mesoscopic lattice Boltzmann fluid model to the microscopic molecular dynamics model of cell movement is elucidated. A treatment of red blood cells as extended structures, a method to handle highly irregular geometries through topology driven graph partitioning, and an efficient molecular dynamics load balancing scheme are introduced. These result in a large-scale simulation of the cardiovascular system, with a realistic description of the complex human arterial geometry, from centimeters down to the spatial resolution of red-blood cells. The computational methods developed to enable scaling of the application to 294,912 processors are discussed, thus empowering the simulation of a full heartbeat.

Second, further extensions to enable the modeling of fluids in vessels with smaller diameters and a method for introducing the deformational forces exerted on the arterial flows from the movement of the heart by borrowing concepts from cosmodynamics are presented. These additional forces have a great impact on the endothelial shear stress. Third, the fluid model is extended to not only recover Navier-Stokes hydrodynamics, but also a wider range of Knudsen numbers, which is especially important in micro- and nano-scale flows. The tradeoffs of many optimizations methods such as the use of deep halo level ghost cells that, alongside hybrid programming models, reduce the impact of such higher-order models and enable efficient modeling of extreme regimes of computational fluid dynamics are discussed. Fourth, the extension of these models to other research questions like clogging in microfluidic devices and determining the severity of co-arctation of the aorta is presented. Through this work, a validation of these methods by taking real patient data and the measured pressure value before the narrowing of the aorta and predicting the pressure drop across the co-arctation is shown. Comparison with the measured pressure drop in vivo highlights the accuracy and potential impact of such patient specific simulations.

Finally, a method to enable the simulation of longer trajectories in time by discretizing both spatially and temporally is presented. In this method, a serial coarse iterator is used to initialize data at discrete time steps for a fine model that runs in parallel. This coarse solver is based on a larger time step and typically a coarser discretization in space. Iterative refinement enables the compute-intensive fine iterator to be modeled with temporal parallelization. The algorithm consists of a series of prediction-corrector iterations completing when the results have converged within a certain tolerance. Combined, these developments allow large fluid models to be simulated for longer time durations than previously possible.

Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries (RV-PA) in pulmonary atresia and truncus arteriosus. Currently available options are fixed size and have limited durability. Hence, multiple re-operations are required to match the patients’ growth and address structural deterioration of the conduit. Moreover, the pre-set shape of these implants increases the complexity of operation to accommodate patient specific anatomy. The goal of the research group is to address these limitations by 3D printing geometrically customised implants with growth capacity. In this study, patient-specific geometrical models of the heart were constructed by segmenting MRI data of patients using Mimics inPrint 2.0. Computational Fluid Dynamics (CFD) analysis was performed, using ANSYS CFX, to design customised geometries with better haemodynamic performance. CFD simulations showed that customisation of a replacement RV-PA conduit can improve its performance. For instance, mechanical energy dissipation and wall shear stress can be significantly reduced. Finite Element modelling also allowed prediction of the suitable thickness of a synthetic material to replicate the behaviour of pulmonary artery wall under arterial pressures. Hence, eliminating costly and time-consuming experiments based on trial-and-error. In conclusion, it is shown that patient-specific design is feasible, and these designs are likely to improve the flow dynamics of the RV-PA connection. Modelling also provides information for optimisation of biomaterial. In time, 3D printing a customised implant may simplify replacement procedures and potentially reduce the number of operations required over a life time, bringing substantial improvements in quality of life to the patients

Background: Single ventricle congenital heart defects with cyanotic mixing between systemic and pulmonary circulations afflict 2 per 1000 live births. Following the atriopulmonary connection proposed by Fontan and Baudet in 1971, the present procedure is the total cavopulmonary connection (TCPC), where the superior vena cava (SVC) and inferior vena cava (IVC) are sutured to the left pulmonary artery (LPA) and right pulmonary artery (RPA). However, surgeon preference dictates the implementation of the extra-cardiac and intra-atrial varieties of the TCPC. Overall efficiency and hemodynamic advantage of the competing methodologies have not been determined. Hypothesis: It is hypothesized that an understanding of the experimental fluid dynamic differences between various Fontan surgical methodologies in the TCPC allows for power loss evaluation toward improved surgical planning and design. Methods: Toward such analysis, a previously developed data processing methodology is applied to create an anatomic database of single ventricle patients from in vivo magnetic resonance imaging (MRI) to examine the gamut of TCPC anatomies. From stereolithographic models of representative cases, pressure and flow data are used to quantify control volume power loss to measure overall efficiency. particle image velocimetry (PIV) is employed to detail flow structures in the vasculature. Results are validated with dye injection flow visualization and 3-D phase contrast magnetic resonance imaging (PC-MRI) velocimetry, highlighting flow phenomena that cannot be captured with in vivo MRI due to prohibitively long scanning times. Preliminary results illustrate the variation of control volume power loss over several TCPC anatomies with varying flow conditions, the application of PIV, and validation approaches with 3-D PC-MRI velocimetry. Data from control volume power loss evaluation demonstrate a correlation with TCPC anatomy, providing added clinical knowledge of optimal TCPC design. Findings from PIV and 3-D PC-MRI velocimetry reveal a means for quantitatively comparing flow structure. Dye injection flow visualization offers qualitative insight into limitations of the selected velocimetry techniques.

This research focuses on the development of a biomechanical strategy for risk assessment of atherosclerotic plaque rupture, which is a leading cause of acute cardiovascular events, such as heart attack and stroke. Image-based three-dimensional coronary and carotid arterial models were developed, and computational biomechanical analysis was performed to evaluate the mechanical interaction between blood flow and atherosclerosis. This study uncovered the biomechanical risk factors that are associated with high-risk atherosclerosis and provided a biomechanical tool for detecting high-risk plaques. It will help with future clinical diagnosis and treatment of cardiovascular diseases.

L'utilisation d'Assistance Circulatoire Mécanique (ACM) augmente dans le cas d'insuffisance cardiaque terminale ne répondant pas aux traitements médicaux. Dans ce contexte nous avons: 1) présenté une vue d'ensemble des problématiques cliniques, 2) élaboré une nouvelle approche de planification assistée par ordinateur pour l'implantation d'ACM, 3) implémenté un modèle CFD pour comprendre l'hémodynamique ventriculaire induite par la canule apicale. Afin de diminuer les complications, des critères quantitatifs optimisant la décharge ventriculaire pourraient être déterminés par CFD. La planification fournirait des informations permettant de choisir le dispositif et adapter la stratégie clinique
Mechanical Circulatory Support (MCS) therapy is increasingly considered for patients with advanced heart failure unresponsive to optimal medical treatments. In this context, we: 1) presented an overview of clinical issues raised by MCS implantation, 2) designed a novel computer-assisted approach for planning the implantation, 3) implemented a CFD model to understand the ventricle hemodynamics induced by the inflow cannula pose. With the aim of decreasing complications and morbidity, quantitative criteria for optimizing ventricle unloading could be determined through CFD, and the planning approach may provide valuable information for choosing the device and adapting the clinical strategy

Defective or diseased native valves have been replaced by bileaflet mechanical heart valves (BMHVs) for many years. However, severe complications still exist, and thus blood damage that occurs in BMHV flows must be well understood. The aim of this research is to numerically study platelet damage that occurs in BMHV flows. The numerical suspension flow method combines lattice-Boltzmann fluid modeling with the external boundary force method. This method is validated as a general suspension flow solver, and then validated against experimental BMHV flow data. Blood damage is evaluated for a physiologic adult case of BMHV flow and then for BMHVs with pediatric sizing and flow conditions. Simulations reveal intricate, small-scale BMHV flow features, and the presence of turbulence in BMHV flow. The results suggest a shift from previous evaluations of instantaneous flow to the determination of long-term flow recirculation regions when assessing thromboembolic potential. Sharp geometries that may induce these recirculation regions should be avoided in device design. Simulations for predictive assessment of pediatric sized valves show increased platelet damage values for potential pediatric valves. However, damage values do not exceed platelet activation thresholds, and highly damaged platelets are found far from the valve. Thus, the increased damage associated with resized valves is not such that pediatric valve development should be hindered. This method can also be used as a generic tool for future evaluation of novel prosthetic devices or cardiovascular flow problems.

En imagerie cardiovasculaire, un biomarqueur est une information quantitative permettant d'établir une corrélation avec la présence ou le développement d'une pathologie cardiovasculaire. Ces biomarqueurs sont généralement obtenus grâce à l'imagerie de l'anatomie et du flux sanguin. Récemment, la séquence d'acquisition d'IRM de flux 4D a ouvert la voie à la mesure du flux sanguin dans un volume 3D au cours du cycle cardiaque. Or, ce type d'acquisition résulte d'un compromis entre le rapport signal sur bruit, la résolution et le temps d'acquisition. Le temps d'acquisition est limité et par conséquent les données sont bruitées et sous-résolues. Dans ce contexte, la quantification de biomarqueurs est difficile. L'objectif de cette thèse est d'améliorer la quantification de biomarqueurs et en particulier du cisaillement à la paroi. Deux stratégies ont été mises en œuvre pour atteindre cet objectif. Une première solution permettant le filtrage spatio-temporel du champ de vitesse a été proposée. Cette dernière a révélé l'importance de la paroi dans la modélisation d'un champ de vitesse. Une seconde approche, constituant la contribution majeure de cette thèse, s'est focalisée sur la conception d'un algorithme estimant le cisaillement à la paroi. L'algorithme, nommé PaLMA, s'appuie sur la modélisation locale de la paroi pour construire un modèle de vitesse autour d'un point d'intérêt. Le cisaillement est évalué à partir du modèle de la vitesse. Cet algorithme intègre une étape de régularisation a posteriori améliorant la quantification du cisaillement à la paroi. Par ailleurs, une approximation du filtre IRM est utilisée pour la première fois pour l'estimation du cisaillement. Enfin, cet algorithme a été évalué sur des données synthétiques, avec des écoulements complexes au sein de carotides, en fonction du niveau de bruit, de la résolution et de la segmentation. Il permet d'atteindre des performances supérieures à une méthode de référence dans le domaine, dans un contexte représentatif de la pratique clinique
In cardiovascular imaging, a biomarker is quantitative information correlated with an existing or growing cardiovascular pathology. Biomarkers are generally obtained by anatomy and blood flow imaging. Recently, the 4D Flow MRI sequence opened new opportunities in measuring the blood flow within a 3D volume along the cardiac cycle. However, this sequence is a compromise between signalto-noise ratio, resolution and acquisition time. Allocated time being limited, velocity measurements are noisy and low resolution. In that context, biomarkers' quantification is challenging. This thesis's purpose is to enhance biomarkers' quantification and particularly for the wall shear stress (WSS). Two strategies have been investigated to reach that objective. A first solution allowing the spatiotemporal filtering of the velocity field has been proposed. It revealed the importance of the wall for the velocity field modelization. A second approach, being the major contribution of this work, focused on the design of a WSS quantification algorithm. This algorithm, named PaLMA, is based on the local modelization of the wall to build a velocity model near a point of interest. The WSS is computed from the velocity model. This algorithm embeds an a posteriori regularization step to improve the WSS quantification. Besides, a blurring model of 4D Flow MRI is used for the first time in the WSS quantification context. Finally, this algorithm has been validated over synthetic datasets, with carotids' complex flows, concerning the signal-to-noise ratio, the resolution, and the segmentation. The performances of PaLMA are superior to a reference solution in that domain, within a clinical routine context

A system of 32 first-order differential equations is formulated and solved for the LP model using a fourth-order adaptive Runge-Kutta solver. The output pressure and flow waveforms obtained from the LP model are imposed as boundary conditions on the CFD model. Coupling of the two models is done through an iterative process where the parameters in the LP model are adjusted to match the CFD solution. The CFD model domain is a representative HLHS anatomy of an infant after undergoing the Hybrid Norwood procedure and is comprised of the neo-aorta, pulmonary roots, aortic arch with branching arteries, and pulmonary arteries. The flow field is solved over several cardiac cycles using an implicit-unsteady RANS equation solver with the k-epsilon turbulence model.; Hypoplastic left heart syndrome (HLHS) is a complex cardiac malformation in neonates suffering from congenital heart disease and occurs in nearly 1 per 5000 births. HLHS is uniformly fatal within the first hours or days after birth as the severely malformed anatomies of the left ventricle, mitral and aortic valves, and ascending aorta are not compatible with life. The regularly implemented treatment, the Norwood operation, is a complex open heart procedure that attempts to establish univentricular circulation by removing the atrial septum (communicating the right and left ventricle), reconstructing the malformed aortic arch, and connecting the main pulmonary artery into the reconstructed arch to allow direct perfusion from the right ventricle into the systemic circulation. A relatively new treatment being utilized, the Hybrid Norwood procedure, involves a less invasive strategy to establish univentricular circulation that avoids a cardiopulmonary bypass (heart-lung machine), deliberate cardiac arrest, and circulatory arrest of the patient during the procedure. The resulting systemic-pulmonary circulation is unconventional; blood is pumped simultaneously and in parallel to the systemic and pulmonary arteries after the procedure. Cardiac surgeons are deeply interested in understanding the global and local hemodynamics of this anatomical configuration. To this end, a multiscale model of the entire circulatory system was developed utilizing an electrical lumped parameter model for the peripheral or distal circulation coupled with a 3D Computational Fluid Dynamics (CFD) model to understand the local hemodynamics. The lumped parameter (LP) model is mainly a closed loop circuit comprised of RLC compartments that model cardiac function as well as the viscous drag, flow inertia, and compliance of the different arterial and venous beds in the body.
ID: 030423155; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2011.; Includes bibliographical references (p. 59-61).
M.S.
Masters
Mechanical, Materials, and Aerospace Engineering
Engineering and Computer Science

The thesis presents a fluid-structure interaction studies on the hemodynamics of blood flow in the left ventricle and through the mitral valve. The virtual model consists of a mathematical model of the left ventricle coupled with a complex and structurally flexible bi-leaflet valve representing the mitral opening. The mitral valve is a bicuspid valve with anterior and posterior leaflets and it regulates unidirectional blood flow from the left atrium to the left ventricle in the diastole phase. The leaflets are made of chordae, annulus and papillary muscles. The goal of this study is to provide biomedical engineers and clinical physicians with a virtual laboratory tool to understand the dynamics of blood flow in a diseased heart and aid in the design of novel artificial heart valves. To this end, the simulation studies present an increasingly complex model of the heart to evaluate the vortex ring formation and evolution of the diastole phase in the left ventricle; and to characterize the septal-anterior motion in a diseased heart with obstructive hypertrophic cardiomyopathy. Finally, in collaboration with an industrial partner, the fluid-structure modeling framework was used to evaluate the performance of a new accelerated artificial valve tester.
Graduate

Knowledge of detailed blood flow characteristics can be extremely valuable in a variety of settings. Examples range from studying disease processes such as atherosclerosis to aiding in the design of medical devices such as prosthetic cardiac valves. For in vivo and optically inaccessible in vitro flows, accurate measurements of velocity fields and shear stresses can be difficult to obtain. Doppler ultrasound and magnetic resonance imaging are the most commonly used techniques, but have important limitations. Recently, there has been increased interest in the application of particle image velocimetry principles towards tracking of ultrasound speckle patterns to determine multidimensional flow velocities with increased temporal resolution. We refer to our implementation as ultrasound speckle image velocimetry (USIV). In this research project, our first objective was to obtain a detailed characterization of the factors unique to ultrasound imaging that can influence the accuracy of velocity measurements. By conducting in vitro experiments with uniform speckle phantom translation as well as steady tube flow, we have shown that characteristics such as transducer focal depth and beam sweep speed as well as particle motion direction and velocity can all influence USIV results. Our second objective was to demonstrate the utility of USIV for analyzing in vivo blood flows. After administering ultrasound contrast agent to anesthetized pigs, we were able to obtain detailed images of both left ventricular flow and abdominal aortic flow. Velocity profiles were measured during both left ventricular filling and ejection. Our most interesting finding was the presence in certain cases of highly asymmetric retrograde flow in the infrarenal aorta. The factors that lead to such flows may have relevance to the development of atherosclerosis and abdominal aneurysms. USIV is likely to be very useful for further studies both in vivo and with in vitro elastic aorta models.

abstract: Aortic pathologies such as coarctation, dissection, and aneurysm represent a particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies and for planning their surgical repair. In vitro experiments are required to validate these simulations against real world data, and a pulsatile flow pump system can provide physiologic flow conditions characteristic of the aorta. This dissertation presents improved experimental techniques for in vitro aortic blood flow and the increasingly larger parts of the human cardiovascular system. Specifically, this work develops new flow management and measurement techniques for cardiovascular flow experiments with the aim to improve clinical evaluation and treatment planning of aortic diseases. The hypothesis of this research is that transient flow driven by a step change in volume flux in a piston-based pulsatile flow pump system behaves differently from transient flow driven by a step change in pressure gradient, the development time being substantially reduced in the former. Due to this difference in behavior, the response to a piston-driven pump can be predicted in order to establish inlet velocity and flow waveforms at a downstream phantom model. The main objectives of this dissertation were: 1) to design, construct, and validate a piston-based flow pump system for aortic flow experiments, 2) to characterize temporal and spatial development of start-up flows driven by a piston pump that produces a step change from zero flow to a constant volume flux in realistic (finite) tube geometries for physiologic Reynolds numbers, and 3) to develop a method to predict downstream velocity and flow waveforms at the inlet of an aortic phantom model and determine the input waveform needed to achieve the intended waveform at the test section. Application of these newly improved flow management tools and measurement techniques were then demonstrated through in vitro experiments in patient-specific coarctation of aorta flow phantom models manufactured in-house and compared to computational simulations to inform and execute future experiments and simulations.
Dissertation/Thesis
Doctoral Dissertation Bioengineering 2015

The mechanisms behind cardiovascular disease (CVD) initiation and progression are not fully elucidated. It is hypothesized that blood flow patterns regulate endothelial cell (EC) function to affect the progression of CVDs. A system that subjects ECs to physiologically-relevant shear stress waveforms within microfluidic devices has not yet been demonstrated, despite the advantages associated with the use of these devices. In this work, a bioreactor was designed to fulfill this need. Waveforms from regions commonly affected by CVDs including were derived. Pump motion and fluid flow profiles were validated by actuator motion tracking, particle image velocimetry, and flowmeters. While several relevant waveforms were successfully replicated, physiological waveforms could not be produced at physiological frequencies owing to actuator velocity and accuracy limitations, as well as dampening effects in the system. Overall, this work lays the foundation for designing a system that provides insight into the role of shear stress in CVD pathogenesis.