Use of 3D rotational angiography to perform computational fluid dynamics and virtual interventions in aortic coarctation

Computational fluid dynamics (CFD) can be used to analyze blood flow and to predict hemodynamic outcomes after interventions for coarctation of the aorta and other cardiovascular diseases. We report the first use of cardiac 3‐dimensional rotational angiography for CFD and show not only feasibility but also validation of its hemodynamic computations with catheter‐based measurements in three patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154333/1/ccd28507.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154333/2/ccd28507_am.pd

A Coupled Experimental and Computational Approach to Quantify Deleterious Hemodynamics, Vascular Alterations, and Mechanisms of Long-Term Morbidity in Response to Aortic Coarctati

Introduction Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. Methods Rabbits underwent thoracic CoA at 10 weeks of age (~ 9 human years) to induce a 20 mm Hg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32 weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. Results Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12 weeks of normal BP (~ 4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. Discussion These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods

IN VITRO MULTI-SCALE PATIENT-SPECIFIC MODELING OF HEMODYNAMICS IN STAGE 1 NORWOOD PALLIATION FOR THE TREATMENT OF SINGLE VENTRICLE HEART DISEASE

Hypoplastic left heart syndrome (HLHS) is a congenital heart defect in which the left ventricle is severely underdeveloped. The Norwood procedure is the first stage procedure to make an unrestrictive systemic blood flow and at the same time balance it with the pulmonary flow. This is done by constructing a neo-aorta using the pulmonary artery root and the autologous aorta, and then installing a shunt to the pulmonary artery. Variations of the Norwood surgery include the modified Blalock-Taussig (mBT) shunt, which diverts blood from the innominate artery to the pulmonary artery (PA), and the Right Ventricle Shunt (RVS), which diverts blood from the right ventricle to the PA. Recurrent neo-aortic coarctation (NAO) is a frequent complication of the Norwood procedure. It causes changes in circulation flow rate balances and hypertension in the aortic arch. Conventionally, the value of a coarctation index (CoI) is used in choosing interventions to treat NAO. Aortic arch morphology of Norwood patients is suspected to be a factor of hemodynamic response to NAO. This study aims to develop and validate an in vitro model of the Norwood circulation and to use it to better understand the hemodynamic impact of progressive coarctation severity in the Norwood patients with mBT and RVS shunts. Five patient-specific cases were selected, each case having a different aortic morphology. A multi-scale mock circulatory system (MCS) was developed to simulate patient-specific Norwood circulation. The MCS couples a lumped parameter network (LPN) model of the circulation with the 3D test section of the aorta and superior arteries. The system includes branches for the pulmonary, upper body, lower body and single ventricle. The MCS was set to patient specific conditions based on the clinical measurements. Flow rate and pressure measurements were made around the circulation model. The native arch anatomy of each patient was morphed to simulate coarctation by controlling the amount of narrowing of the aortic isthmus, while keeping the original patient-specific aortic geometry intact. Separate NAO models were created to provide for a range of CoI. Aortic pressure measurements were made to study pressure drop and recovery effects. In a further study, the MCS was modified to simulate the Norwood circulation with RVS. The NAO models were used to study coarctation effects. The MCS was validated against clinical measurements. The experimental measurements demonstrated that the time-based flow rate and pressure developed within the circulation recapitulated clinical measurements (0.72 \u3c R2 \u3c 0.95). The results showed good fidelity in replicating the mean values of the Norwood circulation at the patient-specific level (p \u3e 0.10). The system demonstrated the coarctation effects in the Norwood circulation with mBT. For all patient cases, the single ventricle power (SVP), mean pressure difference, and Qp/Qs increased noticeably when CoI \u3c 0.5 (p\u3c0.05). An increased SVP correlated with abnormal aortic arch morphology (dilated or tubular). Measurements from two of four cases studied showed that substituting the mBT with the RVS can relieve pulmonary overcirculation and improve the pulmonary to systemic flow balance (Qp/Qs). Using the RVS reduced SVP requirements by 74.5 mW on average. A tubular arch morphology was associated with a higher SVP with the RVS than those patients with a dilated arch. The study has shown that the hypothesis, “NAO may not need immediate surgical intervention at an early stage for some patients†was accepted. Aortic arch morphology does affect the hemodynamic response to NAO. Any morphological abnormality causes extra SVP. The RVS can relieve overcirculation and is associated with lower SVP level and SVP changes in some of the patients

Effects of Uncertainty of Outlet Boundary Conditions in a Patient-Specific Case of Aortic Coarctation

Computational Fluid Dynamics (CFD) simulations of blood flow are widely used to compute a variety of hemodynamic indicators such as velocity, time-varying wall shear stress, pressure drop, and energy losses. One of the major advances of this approach is that it is non-invasive. The accuracy of the cardiovascular simulations depends directly on the level of certainty on input parameters due to the modelling assumptions or computational settings. Physiologically suitable boundary conditions at the inlet and outlet of the computational domain are needed to perform a patient-specific CFD analysis. These conditions are often affected by uncertainties, whose impact can be quantified through a stochastic approach. A methodology based on a full propagation of the uncertainty from clinical data to model results is proposed here. It was possible to estimate the confidence associated with model predictions, differently than by deterministic simulations. We evaluated the effect of using three-element Windkessel models as the outflow boundary conditions of a patient-specific aortic coarctation model. A parameter was introduced to calibrate the resistances of the Windkessel model at the outlets. The generalized Polynomial Chaos method was adopted to perform the stochastic analysis, starting from a few deterministic simulations. Our results show that the uncertainty of the input parameter gave a remarkable variability on the volume flow rate waveform at the systolic peak simulating the conditions before the treatment. The same uncertain parameter had a slighter effect on other quantities of interest, such as the pressure gradient. Furthermore, the results highlight that the fine-tuning of Windkessel resistances is not necessary to simulate the post-stenting scenario

On Coupling a Lumped Parameter Heart Model and a Three-Dimensional Finite Element Aorta Model

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions

Computational fluid dynamics indicators to improve cardiovascular pathologies

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.Postprint (published version

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

Tuning of boundary conditions parameters for hemodynamics simulation using patient data

This thesis describes an engineering workflow, which allows specification of boundary conditions and 3D simulation based on clinically available patient-specific data. A review of numerical models used to describe the cardiovascular system is provided, with a particular focus on the clinical target disease chosen for the toolkit, aortic coarctation. Aorta coarctation is the fifth most common congenital heart disease, characterized by a localized stenosis of the descending thoracic aorta. Current diagnosis uses invasive pressure measurement with rare but potential complications. The principal objective of this work was to develop a tool that can be translated into the clinic, requiring minimum operator input and time, capable of returning meaningful results from data typically acquired in clinical practice. Linear and nonlinear 1D modelling approaches are described, tested against full 3D solutions derived for idealized geometries of increasing complexityand for a patient-specific aortic coarctation. The 1D linear implementation is able to represent the fluid dynamic in simple idealized benchmarks with a limited effort in terms of computational time, but in a more complex case, such as a mild aortic coarctation, it is unable to predict well 3D fluid dynamic features. On the other side, the 1D nonlinear implementation showed a good agreement when compared to 3D pressure and flow waveforms, making it suitable to estimate outflow boundary conditions for subject-specific models. A cohort of 11 coarctation patients was initially used for a preliminary analysis using 0D models of increasing complexity to examine parameters derived when tuning models of the peripheral circulation. The first circuit represents the aortic coarctation as a nonlinear resistance, using the Bernoulli pressure drop equation, without considering the effect of downstream circulation. The second circuit include a peripheral resistance and compliance, and separate ascending and descending aortic pressure responses. In the third circuit a supra-aortic Windkessel model was added in order to include the supra-aortic circulation. The analysis detailed represents a first attempt to assess the interaction between local aortic haemodynamics and subject-specific parameterization of windkessel representations of the peripheral and supra-aortic circulation using clinically measured data. From the analysis of these 0D models, it is clear that the significance of the coarctation becomes less from the simple two resistance model to the inclusion of both the peripheral and supra-aortic circulation. These results provide a context within which to interpret outcomes of the tuning process reported for a more complex model of aortic haemodynamics using 1D and 3D model approaches. Earlier developments are combined to enable a multi-scale modelling approach to simulate fluid-dynamics. This includes non-linear 1D models to derive patient-specific parameters for the peripheral and supra-aortic circulation followed by transient analysis of a coupled 3D/0D system to estimate the coarctation pressure augmentation. These predictions are compared with invasively measured catheter data and the influence of uncertainty in measured data on the tuning process is discussed. This study has demonstrated the feasibility of constructing a workflow using non-invasive routinely collected clinical data to predict the pressure gradient in coarctation patients using patient specific CFD simulation, with relatively low levels of user interaction required. The results showed that the model is not suitable for the clinical use at this stage, thus further work is required to enhance the tuning process to improve agreement with measured catheter data. Finally, a preliminary approach for the assessment of change in haemodynamics following coarctation repair, where the coarctation region is enlarged through a virtual intervention process. The CFD approach reported can be expanded to explore the sensitivity of the peak ascending aortic pressure and descending aortic flow to the aortic diameter achieved following intervention, such an analysis would provide guidance for surgical intervention to target the optimal diameter to restore peripheral perfusion and reduce cerebral hypertension