Finite Element Analysis to Study Percutaneous Heart Valves

Communications engineering / telecommunication

A Collagen‐Glycosaminoglycan‐Fibrin Scaffold For Heart Valve Tissue Engineering Applications

The field of heart valve biology and tissue engineering a heart valve continue to expand. The presentatio ns at this meeting reflect the advances made in both areas due to the multi-disciplinary approach taken by many laboratories

In-Vitro and In-Silico Investigations of Alternative Surgical Techniques for Single Ventricular Disease

Single ventricle (SV) anomalies account for one-fourth of all cases of congenital Heart disease. The conventional second and third stage i.e. Comprehensive stage II and Fontan procedure of the existing three-staged surgical approach serving as a palliative treatment for this anomaly, entails multiple complications and achieves a survival rate of 50%. Hence, to reduce the morbidity and mortality rate associated with the second and third stages of the existing palliative procedure, the novel alternative techniques called “Hybrid Comprehensive Stage II” (HCSII), and a “Self-powered Fontan circulation” have been proposed. The goal of this research is to conduct in-vitro investigations to validate computational and clinical findings on these proposed novel surgical techniques. The research involves the development of a benchtop study of HCSII and self-powered Fontan circulation

Application of engineering methodologies to address patient-specific clinical questions in congenital heart disease

The recent advances in medical imaging and in computer technologies have improved the prediction capabilities of biomechanical models. In order to replicate physiological, pathological or surgically corrected portions of the cardiovascular system, several engineering methodologies and their combinations can be adopted. Specifically, in this thesis, 3D reconstructions of patient-specific implanted devices and cardiovascular anatomies have been realised using both volumetric and biplanar visualisation methods, such as CT, MR, 4D-MR Flow and fluoroscopy. Finite Element techniques have been used to computationally deploy cardiovascular endoprosthesis, such as stents and percutaneous pulmonary valve devices, under patient-specific boundary conditions. To analyse pressure and velocity fields occurring in patient-specific vessel anatomies under patient-specific conditions, Lumped Parameter Networks and Computational Fluid Dynamics simulations have been employed. The above mentioned engineering tools have been here applied to address three clinical topics: 1 - Percutaneous pulmonary valve implantation (PPVI) Nowadays, more than 5,000 patients with pulmonary valve dysfunctions have been treated successfully with a percutaneous device, consisting in a bovine jugular venous valve sewn inside a balloon expandable stent. However, 25% of the treated patients experienced stent fracture. Using a novel methodological patient-specific approach that combines 3D reconstructions of the implanted stent from patients’ biplane fluoroscopy images and FE analyses, I carried out a risk stratification for stent fracture prediction. 2 - Transposition of the Great Arteries (TGA) Patients born with the congenital heart defect TGA need a surgical correction, which however, is associated with long term complications: the enlargement of the aortic root, and the development of a unilateral pulmonary stenosis. These may originate a complex hemodynamics that I tried to investigate by using patient-specific LPN and CFD models. 3 - Aortic Coarctation (CoA) Finally, combinations of FE and CFD-LPN models have been used to plan treatment in a patient with CoA and aberrant right subclavian

DEVELOPMENT AND IMPLEMENTATION OF NOVEL STRATEGIES TO EXPLOIT 3D ULTRASOUND IMAGING IN CARDIOVASCULAR COMPUTATIONAL BIOMECHANICS

Introduction In the past two decades, major advances have been made in cardiovascular diseases assessment and treatment owing to the advent of sophisticated and more accurate imaging techniques, allowing for better understanding the complexity of 3D anatomical cardiovascular structures1. Volumetric acquisition enables the visualization of cardiac districts from virtually any perspective, better appreciating patient-specific anatomical complexity, as well as an accurate quantitative functional evaluation of chamber volumes and mass avoiding geometric assumptions2. Additionally, this scenario also allowed the evolution from generic to patient-specific 3D cardiac models that, based on in vivo imaging, faithfully represent the anatomy and different cardiac features of a given alive subject, being pivotal either in diagnosis and in planning guidance3. Precise morphological and functional knowledge about either the heart valves\u2019 apparatus and the surrounding structures is crucial when dealing with diagnosis as well as preprocedural planning4. To date, computed tomography (CT) and real-time 3D echocardiography (rt3DE) are typically exploited in this scenario since they allow for encoding comprehensive structural and dynamic information even in the fourth dimension (i.e., time)5,6. However, owing to its cost-effectiveness and very low invasiveness, 3D echocardiography has become the method of choice in most situations for performing the evaluation of cardiac function, developing geometrical models which can provide quantitative anatomical assessment7. Complementing this scenario, computational models have been introduced as numerical engineering tools aiming at adding qualitative and quantitative information on the biomechanical behavior in terms of stress-strain response and other multifactorial parameters8. In particular, over the two last decades, their applications have been ranging from elucidating the heart biomechanics underlying different patho-physiological conditions9 to predicting the effects of either surgical or percutaneous procedures, even comparing several implantation techniques and devices10. At the early stage, most of the studies focused on FE modeling in cardiac environment were based on paradigmatic models11\u201315, being mainly exploited to explore and investigate biomechanical alterations following a specific pathological scenario or again to better understand whether a surgical treatment is better or worse than another one. Differently, nowadays the current generation of computational models heavily exploits the detailed anatomical information yielded by medical imaging to provide patient-specific analyses, paving the way toward the development of virtual surgical-planning tools16\u201319. In this direction, cardiac magnetic resonance (CMR) and CT/micro-CT are the mostly accomplished imaging modality, since they can provide well-defined images thanks to their spatial and temporal resolutions20\u201325. Nonetheless, they cannot be applied routinely in clinical practice, as it can be differently done with rt3DE, progressively became the modality of choice26 since it has no harmful effects on the patient and no radiopaque contrast agent is needed. Despite these advantages, 3D volumetric ultrasound imaging shows intrinsic limitations beyond its limited resolution: i) the deficiency of morphological detail owing to either not so easy achievable detection (e.g., tricuspid valve) or not proper acoustic window, ii) the challenge of tailoring computational models to the patient-specific scenario mimicking the morphology as well as the functionality of the investigated cardiac district (e.g., tethering effect exerted by chordal apparatus in mitral valve insufficiency associated to left ventricular dilation), and iii) the needing to systematically analyse devices performances when dealing with real-life cases where ultrasound imaging is the only performable technique but lacking of standardized acquisition protocol. Main findings In the just described scenario, the main aim of this work was focused on the implementation, development and testing of numerical strategies in order to overcome issues when dealing with 3D ultrasound imaging exploitation towards predictive patient-specific modelling approaches focused on both morphological and biomechanical analyses. Specifically, the first specific objective was the development of a novel approach integrating in vitro imaging and finite element (FE) modeling to evaluate tricuspid valve (TV) biomechanics, facing with the lack of information on anatomical features owing to the clinically evident demanding detection of this anatomical district through in vivo imaging. \u2022 An innovative and semi-automated framework was implemented to generate 3D model of TV, to quantitively describe its 3D morphology and to assess its biomechanical behaviour. At this aim, an image-based in vitro experimental approach was integrated with numerical models based on FE strategy. Experimental measurements directly performed on the benchmark (mock circulation loop) were compared with geometrical features computed on the 3D reconstructed model, pinpointing a global good consistency. Furthermore, obtained realistic reconstructions were used as the input of the FE models, even accounting for proper description of TV leaflets\u2019 anisotropic mechanical response. As done experimentally, simulations reproduced both \u201cincompetent\u201d (FTR) and \u201ccompetent-induced\u201d (PMA), proving the efficiency of such a treatment and suggesting translational potential to the clinic. The second specific aim was the implementation of a computational framework able to reproduce a functionally equivalent model of the mitral valve (MV) sub-valvular apparatus through chordae tendineae topology optimization, aiming at chordae rest length arrangement to be able to include their pre-stress state associated to specific ventricular conformation. \u2022 We sought to establish a framework to build geometrically tractable, functionally equivalent models of the MV chordae tendineae, addressing one of the main topics of the computational scientific literature towards the development of faithful patient-specific models from in vivo imaging. Exploiting the mass spring model (MSM) approach, an iterative tool was proposed aiming to the topology optimization of a paradigmatic chordal apparatus of MVs affected by functional regurgitation, in order to be able to equivalently account for tethering effect exerted by the chordae themselves. The results have shown that the algorithm actually lowered the error between the simulated valve and ground truth data, although the intensity of this improvement is strongly valve-dependent.Finally, the last specific aim was the creation of a numerical strategy able to allow for patient-specific geometrical reconstruction both pre- and post- LVAD implantation, in a specific high-risk clinical scenario being rt3DE the only available imaging technique to be used but without any acquisition protocol. \u2022 We proposed a numerical approach which allowed for a systematic and selective analysis of the mechanism associated to intraventricular thrombus formation and thrombogenic complications in a LVAD-treated dilated left ventricle (LV). Ad-hoc geometry reconstruction workflow was implemented to overcome limitations associated to imaging acquisition in this specific scenario, thus being able to generate computational model of the LV assisted with LVAD. In details, results suggested that blood stasis is influenced either by LVAD flow rate and, to a greater extent, by LV residual contractility, being the positioning of the inflow cannula insertion mandatory to be considered when dealing with LVAD thrombogenic potential assessment

Blood flow dynamics in surviving patients with repaired Tetralogy of Fallot

Tetralogy of Fallot (TOF) is a congenital heart disease that causes structural abnormalities in the pulmonary arteries, which in turn disrupt the blood flow. Surgical repair is necessary early in childhood, but chronic complications are common in the adult surviving patients. Pulmonary valve replacement is an operation performed in the repaired TOF (rTOF) patients to overcome the right ventricular overload, but the optimal timing remains a challenge. The main research question is whether the haemodynamic environment of the pulmonary junction can clarify the interplay between the upstream and downstream pulmonary vasculature. Therefore, an extensive analysis of the effect of morphological and flow characteristics in healthy and rTOF models was performed, under various boundary conditions (BCs). The effects of branch angle and origin, branch stenosis, flow splits and pulmonary resistance were investigated in idealised two-dimensional geometries, representative of healthy and rTOF cases, explaining the elevated pressure in the LPA, and clearly showing that downstream pressure and peripheral resistance alter the flow development and the flow split between the two daughter branches. Various modelling parameters were also tested, demonstrating the importance of the valve, and how it disturbs the flow patterns along the MPA. The elasticity of arterial wall had a minimal effect on the flow development while the WSS deviated based on the rheological model assumed. Finally, anatomically realistic three-dimensional models of rTOF patients and healthy volunteers were reconstructed and morphological and flow features were analysed. Higher curvature and tortuosity were correlated with more complex secondary flow patterns, and higher Reynolds and Dean numbers, with increased regions of time-averaged wall shear stress. More importantly, the importance of patient-specificity in the rTOF models, and the variability of the geometric and flow characteristics within the population was highlighted, contrary to the observations in the healthy models. The results of this work could help clinicians evaluate the haemodynamic environment in the rTOF population and potentially predict patients at higher risk, prior to the appearance of severe complications.Tetralogy of Fallot (TOF) is a congenital heart disease that causes structural abnormalities in the pulmonary arteries, which in turn disrupt the blood flow. Surgical repair is necessary early in childhood, but chronic complications are common in the adult surviving patients. Pulmonary valve replacement is an operation performed in the repaired TOF (rTOF) patients to overcome the right ventricular overload, but the optimal timing remains a challenge. The main research question is whether the haemodynamic environment of the pulmonary junction can clarify the interplay between the upstream and downstream pulmonary vasculature. Therefore, an extensive analysis of the effect of morphological and flow characteristics in healthy and rTOF models was performed, under various boundary conditions (BCs). The effects of branch angle and origin, branch stenosis, flow splits and pulmonary resistance were investigated in idealised two-dimensional geometries, representative of healthy and rTOF cases, explaining the elevated pressure in the LPA, and clearly showing that downstream pressure and peripheral resistance alter the flow development and the flow split between the two daughter branches. Various modelling parameters were also tested, demonstrating the importance of the valve, and how it disturbs the flow patterns along the MPA. The elasticity of arterial wall had a minimal effect on the flow development while the WSS deviated based on the rheological model assumed. Finally, anatomically realistic three-dimensional models of rTOF patients and healthy volunteers were reconstructed and morphological and flow features were analysed. Higher curvature and tortuosity were correlated with more complex secondary flow patterns, and higher Reynolds and Dean numbers, with increased regions of time-averaged wall shear stress. More importantly, the importance of patient-specificity in the rTOF models, and the variability of the geometric and flow characteristics within the population was highlighted, contrary to the observations in the healthy models. The results of this work could help clinicians evaluate the haemodynamic environment in the rTOF population and potentially predict patients at higher risk, prior to the appearance of severe complications

Bicuspid aortic valve and associated aortopathy: a combined biomechanics, histological and genetic analysis

Bicuspid aortic valve (BAV) is the most common inborn heart defect and a continuum of a disease process affecting the aortic valve and the thoracic aorta with an increased risk of thoracic aortic aneurysm (TAA) formation and dissection. Aortic dilatation may be related to haemodynamic perturbations or intrinsic wall abnormalities. The aim of this thesis was to investigate the relative contribution of these parameters to BAV aortopathy via integrated analyses. Distribution of circumferential stress in the aorta of BAV patients planned to undergo surgery was analysed using computed tomography imaging and computational modelling. During surgery, aortic biopsies were taken from discrete areas and examined for histological abnormalities. Maximal mechanical stress occurred in the medial ascending aorta in the majority of cases with integrated analyses exhibiting a positive correlation between aortic fibrosis and mechanical stress, both in the root and the ascending aorta. The degree of histological abnormalities and transforming growth factor beta (TGFβ) activation was also assessed in collected tissue biopsies. Patients with either root dilatation and/or predominant regurgitant valve disease had greater levels of medial wall degeneration in their ascending aorta whereas enhanced TGFβ signalling was present in aneurysmal but also, non-dilated BAV aortic segments, pointing to a genetic trigger. Copy number variation (CNV) analyses in a larger BAV cohort revealed a large heterozygous deletion in the angiotensin converting enzyme (ACE) gene and targeted next-generation sequencing revealed previously reported variants in NOTCH1, COL3A1, and APOE genes with additional discovery of a large number of likely pathogenic variants in genes related to BAV formation and aortopathy. In conclusion, different BAV aortic phenotypes were recognised and further analysed. The presence of multiple likely pathogenic variants in sequenced patients suggests a polygenic nature of BAV disease which, in conjuction with local haemodynamic perturbations, supports a mutlifactorial origin of BAV aortopathy.Open Acces

In Vitro Multi Scale Models to Study the Early Stage Circulations for Single Ventricle Heart Diseases Palliations

Single ventricle physiology can result from various congenital heart defects in which the patient has only one functional ventricle. Hypoplastic left heart syndrome refers to patients born with an underdeveloped left ventricle. A three stage palliation strategy is applied over the first several years of life to establish a viable circulation path using the one functioning ventricle. Results of the first stage Norwood procedure on neonates with hypoplastic left heart syndrome are unsatisfactory with high morbidities and mortalities primarily due to high ventricle load and other complications. An early second stage Bidirectional Glenn (BDG) procedure is not a suitable option for neonates due to their high pulmonary vascular resistance (PVR), which limits pulmonary blood flow. Realistic experimental models of these circulations are not well established and would be useful for studying the physiological response to surgical decisions on the distribution of flows to the various territories, so as to predict clinical hemodynamics and guide clinical planning. These would serve well to study novel intervention strategies and the effects of known complications at the local and systems-level. This study proved the hypothesis that it is possible to model accurately the first and second stage palliation circulations using multi-scale in vitro circulation models and to use these models to test novel surgical strategies while including the effects of possible complications. A multi-scale mock circulatory system (MCS), which couples a lumped parameter network model (LPN) of the neonatal circulation with an anatomically accurate three-dimensional model of the surgical anastomosis site, was built to simulate the hemodynamic performance of both the Stage 1 and Stage 2 circulations. A pediatric ventricular assist device was used as the single ventricle and a respiration model was applied to the Stage 2 circulation system. Resulting parameters measured were pressure and flow rates within the various territories, and systemic oxygen delivery (OD) were calculated. The Stage 1 and Stage 2 systems were validated by direct comparisons of time-based and mean pressures and flow rates between the experimental measurements, available clinical recordings and/or CFD simulations. Regression and correlation analyses and unpaired t-tests showed that there was excellent agreement between the clinical and experimental time-based results as measured throughout the circulations (0.60 \u3c R^2 \u3c 0.99; p \u3e 0.05, r.m.s error\u3c 5%). A novel, potentially alternative surgical strategy for the initial palliation, was proposed and was tested, called the assisted bidirectional Glenn (ABG) procedure. The approach taps the higher potential energy of the systemic circulation through a systemic to caval shunt with nozzle to increase pulmonary blood flow and oxygen delivery within a superior cavopulmonary connection. Experimental model was validated against a numerical model (0.65 \u3c sigma \u3c 0.97; p \u3e 0.05). The tested results demonstrated the ABG had two main advantages over the Norwood circulation. First, the flow through the ABG shunt is a fraction of the pulmonary flow, reducing the volume overload on the single ventricle and improving systemic and coronary perfusion. Second, the ABG should provide a more stable source of pulmonary flow, which should reduce thrombotic risk or intimal thickening over an mBT shunt. A study to examine the ejector pump effect was conducted. Two parameters were investigated: (1) the superior vena cava (SVC) and pulmonary artery (PA) pressure difference; and (2) the SVC and PA pressure difference relative to PA flow rate. Results validated the hypothesis that an ejector pump advantage can be adopted in a superior cavo-pulmonary circulation, where the low-energy pulmonary blood flow can be assisted by an additional source of high energy flow from the systemic circulation. But the ejector pump effect produced by the current nozzle designs was not strong. Parametric study includes nozzle size, placement, and nozzle shape was conducted. Results shown that nozzle to shunt diameter ratio had the most important effects on the ABG performance. As β increased, pulmonary artery flow rate and systemic oxygen delivery increased. A suggested β value falls between 0.48 and 0.72. The study showed that a bigger β produced a smaller resistance value. The shape of the nozzle did not change the resistance value. The effects of shunt angle, nozzle placement and nozzle shape on the ABG circulation were not statistical significant. The aortic coarctation study showed that the aortic coarctation could have an effect on the ABG circulation. The coarctation index (CoI) around 0.5 was found to be the transition point between no effects (CoI \u3e 0.5) and discernible effects on the ABG circulation. These effects include changes in pulmonary to systemic flow distribution. In summary, this research verified and validated an in vitro mock circulatory system (MCS) for Stage 1 and Stage 2 circulations. The system was used to assess a novel conceptual surgery option named the ABG. Parametric studies were conducted to give guidance on designing the important element for the ABG: the shunt (nozzle) connecting the SVC and systemic circulation. The performance of the ABG under one unhealthy condition, namely, aortic coarctation was assessed

Computational Fluid Dynamics Investigation of A Novel Hybrid Comprehensive Stage II Operation For Single Ventricle Palliation

Hypoplastic left heart syndrome (HLHS) is a type of heart defect where the left ventricle is underdeveloped or not developed, resulting in only a single functioning right ventricle. Approximately 7.5% of patients with congenital heart disease are born with a single ventricle (SV) which is accompanied by a spectrum of other malformations such as atrophied ascending aorta, atrial septal defects, and ventricular septal defects (VSD). The existing three-hybrid staged surgical approach serving as a palliative treatment for this anomaly entails multiple complications and achieves a survival rate of only 50%. To reduce the trauma associated with the second stage of the hybrid procedure the hybrid comprehensive stage 2 (HCSII) operation can be a novel palliation alternative for a select subset of SV patients with adequate antegrade aortic flow. The procedure reduces surgical trauma in newborns by introducing a stented intrapulmonary baffle to avoid dissection of the pulmonary arteries and reconstruction of the aortic arch while obviating the dissection of the ductal continuation and distal arch. It is the purpose of this dissertation to undertake a computational investigation to elucidate the complex hemodynamics of patients who have undergone HCS II. This was accomplished in a multiscale manner coupling a 0D lumped parameter model (LPM) of the peripheral circulation with 3D pulsatile Computational Fluid Dynamics (CFD) model providing the details and enabling investigation of the HCS II complex hemodynamics. The use of CFD allows modeling of blood flow, the study of the effect of different surgical procedures, suggestion of potential improvements from investigation of areas of concern which are: the pressure drop across the baffle, the loading of the baffle itself, shear stress and shear rates that might lead to thrombus formation, as well as oxygen transport and particle residence time. A 3D anatomical model representative of a patient having undergone the HCSII was rendered utilizing the solid modeling software Solidworks based on anatomical landmarks from CT scans, and a 0D LPM was tuned to produce flowrates and waveforms that matched catheter data. The pulsatile CFD computations were carried out using the commercial STARCCM+ solver. Several cases of baffle strictures relevant to surgical implementations were considered and results showed that the largest pressure drop across the baffle reported was about 3 mmHg while for the same narrowing size and accounting for the distal arch kink, a four-fold increase is observed yielding a 12.15 mmHg drop. Moreover, the analysis showed that for averaged blood flow velocity of 0.5 m/s, no vortex shedding from the baffle was observed in the computational model due to the short distance from the baffle to the aortic arch apex. The velocity and pressure-flow fields were examined at different points throughout the cardia cycle: late diastole, early systole, peak systole, and early diastole. Reverse flow was observed towards late diastolic phase due to the presence of an adverse pressure gradient, and a stagnant flow in the aortic arch apex was also noticed. For the pulmonary circulation and due to the low flow velocity and low pulsatility, the T-junction shape of the SVC presented no risk of recirculation or swirling that may promote thrombogenesis. The wall shear stress on the baffle surface was also reported in pulsatile flow. It was observed that the flow detaches in systole and subsequently reattaches to the baffle surface. Moreover, the baffle surface experiences high wall shear stress magnitudes during systole and uneven distribution of WSS during diastole. The variation in the baffle related narrowing had a little impact on the flow hemodynamics, as shown by the nearly constant oxygen transport across the models. The geometrical modification applied to the models had little effect on the oxygen delivery for up to a 15% change between a 4 mm increment of MPA minimum diameter. The results showed consistency with the published data of Glenn patients. Particle residence time was also reported to identify any blood recirculation or flow stagnation that may lead to platelet activation leading to clot formation rate. On average particles take about 0.5(s) to exit the fluid domain. This time span is equal to the time of one cardiac cycle. Finally, the energy loss and energy efficiency were calculated as a function of split ratio and baffle related narrowing. Across all models, the efficiency was shown to be high