Digital twinning of cardiac electrophysiology for congenital heart disease.

In recent years, blending mechanistic knowledge with machine learning has had a major impact in digital healthcare. In this work, we introduce a computational pipeline to build certified digital replicas of cardiac electrophysiology in paediatric patients with congenital heart disease. We construct the patient-specific geometry by means of semi-automatic segmentation and meshing tools. We generate a dataset of electrophysiology simulations covering cell-to-organ level model parameters and using rigorous mathematical models based on differential equations. We previously proposed Branched Latent Neural Maps (BLNMs) as an accurate and efficient means to recapitulate complex physical processes in a neural network. Here, we employ BLNMs to encode the parametrized temporal dynamics of in silico 12-lead electrocardiograms (ECGs). BLNMs act as a geometry-specific surrogate model of cardiac function for fast and robust parameter estimation to match clinical ECGs in paediatric patients. Identifiability and trustworthiness of calibrated model parameters are assessed by sensitivity analysis and uncertainty quantification.

Analyzing solitary wave solutions of the nonlinear Murray equation for blood flow in vessels with non-uniform wall properties.

Solitary wave solutions are of great interest to bio-mathematicians and other scientists because they provide a basic description of nonlinear phenomena with many practical applications. They provide a strong foundation for the development of novel biological and medical models and therapies because of their remarkable behavior and persistence. They have the potential to improve our comprehension of intricate biological systems and help us create novel therapeutic approaches, which is something that researchers are actively investigating. In this study, solitary wave solutions of the nonlinear Murray equation will be discovered using a modified extended direct algebraic method. These solutions represent a uniform variation in blood vessel shape and diameter that can be used to stimulate blood flow in patients with cardiovascular disease. These solutions are newly in the literature, and give researchers an important tool for grasping complex biological systems. To see how the solitary wave solutions behave, graphs are displayed using Matlab.

Quantitative analysis of hemodynamic changes induced by the discrepancy between the sizes of the flow diverter and parent artery.

The efficacy of flow diverters is influenced by the strut configuration changes resulting from size discrepancies between the stent and the parent artery. This study aimed to quantitatively analyze the impact of size discrepancies between flow diverters and parent arteries on the flow diversion effects, using computational fluid dynamics. Four silicone models with varying parent artery sizes were developed. Real flow diverters were deployed in these models to assess stent configurations at the aneurysm neck. Virtual stents were generated based on these configurations for computational fluid dynamics analysis. The changes in the reduction rate of the hemodynamic parameters were quantified to evaluate the flow diversion effect. Implanting 4.0 mm flow diverters in aneurysm models with parent artery diameters of 3.0-4.5 mm, in 0.5 mm increments, revealed that a shift from oversized to undersized flow diverters led to an increase in the reduction rates of hemodynamic parameter, accompanied by enhanced metal coverage rate and pore density. However, the flow diversion effect observed transitioning from oversizing to matching was less pronounced when moving from matching to undersizing. This emphasizes the importance of proper sizing of flow diverters, considering the benefits of undersizing and not to exceed the threshold of advantages.

Modeling and experimental study of the intervention forces between the guidewire and blood vessels.

A profound investigation of the interaction mechanics between blood vessels and guidewires is necessary to achieve safe intervention. An interactive force model between guidewires and blood vessels is established based on cardiovascular fluid dynamics theory and contact mechanics, considering two intervention phases (straight intervention and contact intervention at a corner named "J-vessel"). The contributing factors of the force model, including intervention conditions, guidewire characteristics, and intravascular environment, are analyzed. A series of experiments were performed to validate the availability of the interactive force model and explore the effects of influential factors on intervention force. The intervention force data were collected using a 2-DOF mechanical testing system instrumented with a force sensor. The guidewire diameter and material were found to significantly impact the intervention force. Additionally, the intervention force was influenced by factors such as blood viscosity, blood vessel wall thickness, blood flow velocity, as well as the interventional velocity and interventional mode. The experiment of the intervention in a coronary artery physical vascular model confirms the practicality validation of the predicted force model and can provide an optimized interventional strategy for vascular interventional surgery. The enhanced intervention strategy has resulted in a considerable reduction of approximately 21.97 % in the force exerted on blood vessels, effectively minimizing the potential for complications associated with the interventional surgery.

Flexural pulse wave velocity in blood vessels.

Arteriosclerosis is a major risk factor for cardiovascular disease and results in arterial vessel stiffening. Velocity estimation of the pulse wave sent by the heart and propagating into the arteries is a widely accepted biomarker. This symmetrical pulse wave propagates at a speed which is related to the Young's modulus through the Moens Korteweg (MK) equation. Recently, an antisymmetric flexural wave has been observed in vivo. Unlike the symmetrical wave, it is highly dispersive. This property offers promising applications for monitoring arterial stiffness and early detection of atheromatous plaque. However, as far as it is known, no equivalent of the MK equation exists for flexural pulse waves. To bridge this gap, a beam based theory was developed, and approximate analytical solutions were reached. An experiment in soft polymer artery phantoms was built to observe the dispersion of flexural waves. A good agreement was found between the analytical expression derived from beam theory and experiments. Moreover, numerical simulations validated wave speed dependence on the elastic and geometric parameters at low frequencies. Clinical applications, such as arterial age estimation and arterial pressure measurement, are foreseen.

Eulerian- lagrangian dense discrete phase model (DDPM) of stenotic LAD coronary arteries in comparison with single phase modeling.

In computational fluid dynamic studies related to blood flow, investigating the behavior of blood particles is crucial, especially red blood cells as they constitute a significant proportion of blood particles. Additionally, studying red blood cell movements is necessary, especially in stenotic artery geometries. A new multiphase scheme was utilized to demonstrate the effect of red blood cells on hemodynamics in complex coronary arteries and investigate the consequence of their motion. To investigate the effect of red blood cell movement on flow, the dense discrete phase model (DDPM) was used. This simulation was performed in 3D coronary arteries with different degrees of stenosis, utilizing blood pressure as inlet and outlet boundary conditions while assuming the arterial wall to be rigid. The model prediction shows good agreement with experimental data. Velocity values were comparable in both single-phase and two-phase flow simulations, but the shear stress in two-phase modeling had higher values. In the two-phase DDPM modeling, the recirculation areas indicated a higher probability of atherosclerosis plaque re-formation in the pre-stenosis area compared to the stenosis and post-stenosis areas. The DDPM model was found to be more effective in obtaining shear stress values in the artery. Additionally, this model provides good results compared to the single-phase model in investigating the movement of particles along the artery as well as recirculation areas that lead to the deposition of particles.

Multiscale computational model of aortic remodeling following postnatal disruption of TGFß signaling.

The healthy adult aorta is a remarkably resilient structure, able to resist relentless cardiac-induced and hemodynamic loads under normal conditions. Fundamental to such mechanical homeostasis is the mechano-sensitive cell signaling that controls gene products and thus the structural integrity of the wall. Mouse models have shown that smooth muscle cell-specific disruption of transforming growth factor-beta (TGFß) signaling during postnatal development compromises this resiliency, rendering the aortic wall susceptible to aneurysm and dissection under normal mechanical loading. By contrast, disruption of such signaling in the adult aorta appears to introduce a vulnerability that remains hidden under normal loading, but manifests under increased loading as experienced during hypertension. We present a multiscale (transcript to tissue) computational model to examine possible reasons for compromised mechanical homeostasis in the adult aorta following reduced TGFß signaling in smooth muscle cells.

Impact of wall thickness on the tissue cooling effect of cryoballoon ablation.

AIMS: Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein (PV) isolation is lacking. The purpose of this study was to delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. METHODS AND RESULTS: A left atrial-PV model was constructed using a three-dimensional printer with data from a patient to which porcine thigh muscle of various thicknesses could be affixed. The model was placed in a 37°C water tank with a PV water flow at a rate that mimicked biological blood flow. Cryofreezing at the PV ostium was performed five times each for sliced porcine thigh muscle of 2, 4, and 6 mm thickness, and sliced muscle cooling on the side opposite the balloon was monitored. The cooling effect was assessed using the average temperature of 12 evenly distributed thermocouples covering the roof region of the left superior PV. Tissue cooling effects were in the order of the 2, 4, and 6 mm thicknesses, with an average temperature of -41.4 ± 4.2°C for 2 mm, -33.0 ± 4.0°C for 4 mm, and 8.0 ± 8.7°C for 6 mm at 180 s (P for trend <0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9°C, 3.9 ± 0.7°C, and 1.3 ± 0.7°C, P for trend <0.0001). CONCLUSION: The cooling effect of cryoballoon freezing is weaker in the deeper layers. Cryoballoon ablation should be performed with consideration to myocardial thickness.

Numerical study of hemodynamic flow in the aortic vessel of Williams syndrome patient with congenital heart disease.

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination.

BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

The impact of small movements with dual lumen cannulae during venovenous extracorporeal membrane oxygenation: A computational fluid dynamics analysis.

BACKGROUND AND OBJECTIVES: Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) provides respiratory support to patients with severe lung disease failing conventional medical therapy. An essential component of the ECMO circuit are the cannulas, which drain and return blood into the body. Despite being anchored to the patient to prevent accidental removal, minor cannula movements are common during ECMO. The clinical and haemodynamic consequences of these small movements are currently unclear. This study investigated the risk of thrombosis and recirculation caused by small movements of a dual lumen cannula (DLC) in an adult using computational fluid dynamics. METHODS: The 3D model of an AVALON Elite DLC (27 Fr) and a patient-specific vena cava and right atrium were generated for an adult patient on ECMO. The baseline cannula position was generated where the return jet enters the tricuspid valve. Alternative cannula positions were obtained by shifting the cannula 5 and 15 mm towards inferior (IVC) and superior (SVC) vena cava, respectively. ECMO settings of 4 L/min blood flow and pulsatile flow at SVC and IVC were applied. Recirculation was defined as a scalar value indicating the infused oxygenated blood inside the drainage lumen, while thrombosis risk was evaluated by shear stress, stagnation volume, washout, and turbulent kinetic energy. RESULTS: Recirculation for all models was less than 3.1 %. DLC movements between -5 to 15 mm increased shear stress and turbulence kinetic energy up to 24.7 % and 11.8 %, respectively, compared to the baseline cannula position leading to a higher predicted thrombosis risk. All models obtained a complete washout after nine seconds except for when the cannula migrated 15 mm into the SVC, indicating persisting stasis and circulating zones. CONCLUSION: In conclusion, small DLC movements were not associated with an increased risk of recirculation. However, they may increase the risk of thrombosis due to increased shear rate, turbulence, and slower washout of blood. Developing effective cannula securement devices may reduce this risk.

Atrial fibrillation increases thrombogenicity of LVAD therapy.

BACKGROUND: This study investigates the hypothesis that presence of atrial fibrillation (AF) in LVAD patients increases thrombogenicity in the left ventricle (LV) and exacerbates stroke risk. METHODS: Using an anatomical LV model implanted with an LVAD inflow cannula, we analyze thrombogenic risk and blood flow patterns in either AF or sinus rhythm (SR) using unsteady computational fluid dynamics (CFD). To analyze platelet activation and thrombogenesis in the LV, hundreds of thousands of platelets are individually tracked to quantify platelet residence time (RT) and shear stress accumulation history (SH). RESULTS: The irregular and chaotic mitral inflow associated with AF results in markedly different intraventricular flow patterns, with profoundly negative impact on blood flow-induced stimuli experienced by platelets as they traverse the LV. Twice as many platelets accumulated very high SH in the LVAD + AF case, resulting in a 36% increase in thrombogenic potential score, relative to the LVAD + SR case. CONCLUSIONS: This supports the hypothesis that AF results in unfavorable blood flow patterns in the LV adding to an increased stroke risk for LVAD + AF patients. Quantification of thrombogenic risk associated with AF for LVAD patients may help guide clinical decision-making on interventions to mitigate the increased risk of thromboembolic events.

ForCEPSS-A framework for cardiac electrophysiology simulations standardization.

BACKGROUND AND OBJECTIVE: Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. METHODS AND RESULTS: Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP1 Plank et al. (2021) and the Python-based carputils2 framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. CONCLUSION: ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.

Effect of veno-arterial extracorporeal membrane oxygenation lower-extremity cannulation on intra-arterial flow characteristics, oxygen content, and thrombosis risk.

PURPOSE: This study aimed to investigate the effects of lower-extremity cannulation on the intra-arterial hemodynamic environment, oxygen content, blood damage, and thrombosis risk under different levels of veno-arterial (V-A) ECMO support. METHODS: Computational fluid dynamics methods were used to investigate the effects of different levels of ECMO support (ECMO flow ratios supplying oxygen-rich blood 100-40 %). Flow rates and oxygen content in each arterial branch were used to determine organ perfusion. A new thrombosis model considering platelet activation and deposition was proposed to determine the platelet activation and thrombosis risk at different levels of ECMO support. A red blood cell damage model was used to explore the risk of hemolysis. RESULTS: Our study found that partial recovery of cardiac function improved the intra-arterial hemodynamic environment, with reduced impingement of the intra-arterial flow field by high-velocity blood flow from the cannula, a flow rate per unit time into each arterial branch closer to physiological levels, and improved perfusion in the lower extremities. Partial recovery of cardiac function helps reduce intra-arterial high shear stress and residence time, thereby reducing blood damage. The overall level of hemolysis and platelet activation in the aorta decreased with the gradual recovery of cardiac contraction function. The areas at high risk of thrombosis under V-A ECMO femoral cannulation support were the aortic root and the area distal to the cannula, which moved to the descending aorta when cardiac function recovered to 40-60 %. However, with the recovery of cardiac contraction function, hypoxic blood pumped by the heart is insufficient in supplying oxygen to the front of the aortic arch, which may result in upper extremity hypoxia. CONCLUSION: We developed a thrombosis risk prediction model applicable to ECMO cannulation and validated the model accuracy using clinical data. Partial recovery of cardiac function contributed to an improvement in the aortic hemodynamic environment and a reduction in the risk of blood damage; however, there is a potential risk of insufficient perfusion of oxygen-rich blood to organs.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part I: Flow configuration and vortex dynamics.

Aortic valve replacement has become an increasing concern due to the rising prevalence of aortic stenosis in an ageing population. Existing replacement options have limitations, necessitating the development of improved prosthetic aortic valves. In this study, flow characteristics during systole in a stenotic aortic valve case are compared with those downstream of two newly designed surgical bioprosthetic aortic valves (BioAVs). To do so, advanced three-dimensional fluid-structure interaction simulations are conducted and dedicated analysis methods to investigate jet flow configuration and vortex dynamics are developed. Our findings reveal that the stenotic case maintains a high jet flow eccentricity due to a fixed orifice geometry, resulting in flow separation and increased vortex stretching and tilting in the commissural low-flow regions. One BioAV design introduces non-axisymmetric leaflet motion, which reduces the maximum jet velocity and forms more vortical structures. The other BioAV design produces a fixed symmetric triangular jet shape due to non-moving leaflets and exhibits favourable vorticity attenuation, revealed by negative temporally and spatially averaged projected vortex stretching values, and significantly reduced drag. Therefore, this study highlights the benefits of custom-designed aortic valves in the context of their replacement through comprehensive and novel flow analyses. The results emphasise the importance of analysing jet flow, vortical structures, momentum balance and vorticity transport for thoroughly evaluating aortic valve performance.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part II: Spectral analysis and anisotropy.

Severe aortic valve stenosis can lead to heart failure and aortic valve replacement (AVR) is the primary treatment. However, increasing prevalence of aortic stenosis cases reveal limitations in current replacement options, necessitating improved prosthetic aortic valves. We investigate flow disturbances downstream of severe aortic stenosis and two bioprosthetic aortic valve (BioAV) designs using advanced energy-based analyses. Three-dimensional high-fidelity fluid-structure interaction simulations have been conducted and a dedicated and novel spectral analysis has been developed to characterise the kinetic energy (KE) carried by eddies in the wavenumber space. In addition, new field quantities, i.e. modal KE anisotropy intensity as well as normalised helicity intensity, are introduced. Spectral analysis shows kinetic energy (KE) decay variations, with the stenotic case aligning with Kolmogorov's theory, while BioAV cases differing. We explore the impact of flow helicity on KE transfer and decay in BioAVs. Probability distributions of modal KE anisotropy unveil flow asymmetries in the stenotic and one BioAV cases. Moreover, an inverse correlation between temporally averaged modal KE anisotropy and normalised instantaneous helicity intensity is noted, with the coefficient of determination varying among the valve configurations. Leaflet dynamics analysis highlights a stronger correlation between flow and biomechanical KE anisotropy in one BioAV due to higher leaflet displacement magnitude. These findings emphasise the role of valve architecture in aortic turbulence as well as its importance for BioAV performance and energy-based design enhancement.

Modelling lower-limb peripheral arterial disease using clinically available datasets: impact of inflow boundary conditions on hemodynamic indices for restenosis prediction.

BACKGROUND AND OBJECTIVES: The integration of hemodynamic markers as risk factors in restenosis prediction models for lower-limb peripheral arteries is hindered by fragmented clinical datasets. Computed tomography (CT) scans enable vessel geometry reconstruction and can be obtained at different times than the Doppler ultrasound (DUS) images, which provide information on blood flow velocity. Computational fluid dynamics (CFD) simulations allow the computation of near-wall hemodynamic indices, whose accuracy depends on the prescribed inlet boundary condition (BC), derived from the DUS images. This study aims to: (i) investigate the impact of different DUS-derived velocity waveforms on CFD results; (ii) test whether the same vessel areas, subjected to altered hemodynamics, can be detected independently of the applied inlet BC; (iii) suggest suitable DUS images to obtain reliable CFD results. METHODS: CFD simulations were conducted on three patients treated with bypass surgery, using patient-specific DUS-derived inlet BCs recorded at either the same or different time points than the CT scan. The impact of the chosen inflow condition on bypass hemodynamics was assessed in terms of wall shear stress (WSS)-derived quantities. Patient-specific critical thresholds for the hemodynamic indices were applied to identify critical luminal areas and compare the results with a reference obtained with a DUS image acquired in close temporal proximity to the CT scan. RESULTS: The main findings indicate that: (i) DUS-derived inlet velocity waveforms acquired at different time points than the CT scan led to statistically significantly different CFD results (p<0.001); (ii) the same luminal surface areas, exposed to low time-averaged WSS, could be identified independently of the applied inlet BCs; (iii) similar outcomes were observed for the other hemodynamic indices if the prescribed inlet velocity waveform had the same shape and comparable systolic acceleration time to the one recorded in close temporal proximity to the CT scan. CONCLUSIONS: Despite a lack of standardised data collection for diseased lower-limb peripheral arteries, an accurate estimation of luminal areas subjected to altered near-wall hemodynamics is possible independently of the applied inlet BC. This holds if the applied inlet waveform shares some characteristics - derivable from the DUS report - as one matching the acquisition time of the CT scan.

Using DFT on ultrasound measurements to determine patient-specific blood flow boundary conditions for computational hemodynamics of intracranial aneurysms.

Boundary conditions (BCs) is one pivotal factor influencing the accuracy of hemodynamic predictions on intracranial aneurysms (IAs) using computational fluid dynamics (CFD) modeling. Unfortunately, a standard procedure to secure accurate BCs for hemodynamic modeling does not exist. To bridge such a knowledge gap, two representative patient-specific IA models (Case-I and Case-II) were reconstructed and their blood flow velocity waveforms in the internal carotid artery (ICA) were measured by ultrasonic techniques and modeled by discrete Fourier transform (DFT). Then, numerical investigations were conducted to explore the appropriate number of samples (N) for DFT modeling to secure the accurate BC by comparing a series of hemodynamic parameters using in-vitro validated CFD modeling. Subsequently, a comprehensive comparison in hemodynamic characteristics under patient-specific BCs and a generalized BC based on a one-dimensional (1D) model was conducted to reinforce the understanding that a patient-specific BC is pivotal for accurate hemodynamic risk evaluations on IA pathophysiology. In addition, the influence of the variance of heart rate/cardiac pulsatile period on hemodynamic characteristics in IA models was studied preliminarily. The results showed that N ≥ 16 for DFT model is a decent choice to secure the proper BC profile to calculate time-averaged hemodynamic parameters, while more data points such as N ≥ 36 can ensure the accuracy of instantaneous hemodynamic predictions. In addition, results revealed the generalized BC could overestimate or underestimate the hemodynamic risks on IAs significantly; thus, patient-specific BCs are highly recommended for hemodynamic modeling for IA risk evaluation. Furthermore, this study discovered the variance of heart rate has rare influences on hemodynamic characteristics in both instantaneous and time-averaged parameters under the assumption of an identical blood flow rate.

Hemodynamics and wall shear metrics in a pulmonary autograft: Comparing a fluid-structure interaction and computational fluid dynamics approach.

OBJECTIVE: In young patients, aortic valve disease is often treated by placement of a pulmonary autograft (PA) which adapts to its new environment through growth and remodeling. To better understand the hemodynamic forces acting on the highly distensible PA in the acute phase after surgery, we developed a fluid-structure interaction (FSI) framework and comprehensively compared hemodynamics and wall shear-stress (WSS) metrics with a computational fluid dynamic (CFD) simulation. METHODS: The FSI framework couples a prestressed non-linear hyperelastic arterial tissue model with a fluid model using the in-house coupling code CoCoNuT. Geometry, material parameters and boundary conditions are based on in-vivo measurements. Hemodynamics, time-averaged WSS (TAWSS), oscillatory shear index (OSI) and topological shear variation index (TSVI) are evaluated qualitatively and quantitatively for 3 different sheeps. RESULTS: Despite systolic-to-diastolic volumetric changes of the PA in the order of 20 %, the point-by-point correlation of TAWSS and OSI obtained through CFD and FSI remains high (r > 0.9, p < 0.01) for TAWSS and (r > 0.8, p < 0.01) for OSI). Instantaneous WSS divergence patterns qualitatively preserve similarities, but large deformations of the PA leads to a decrease of the correlation between FSI and CFD resolved TSVI (r < 0.7, p < 0.01). Moderate co-localization between FSI and CFD is observed for low thresholds of TAWSS and high thresholds of OSI and TSVI. CONCLUSION: FSI might be warranted if we were to use the TSVI as a mechano-biological driver for growth and remodeling of PA due to varying intra-vascular flow structures and near wall hemodynamics because of the large expansion of the PA.

Improved algorithm for generating evenly-spaced streamlines from an orientation field on a triangulated surface.

BACKGROUND: Vector fields such as cardiac fiber orientation can be visualized on a surface using streamlines. The application of evenly-spaced streamline generation to the construction of interconnected cable structure for cardiac propagation models has more stringent requirements imperfectly fulfilled by current algorithms. METHOD: We developed an open-source C++/python package for the placement of evenly-spaced streamlines on a triangulated surface. The new algorithm improves upon previous works by more accurately handling streamline extremities, U-turns and limit cycles, by providing stronger geometrical guarantees on inter-streamline minimal distance, particularly when a high density of streamlines (up to 10µm spacing) is desired, and by making a more efficient parallel implementation available. The approach requires finding intersections between geometrical capsules and triangles to update an occupancy mask defined on the triangles. This enables fast streamline integration from thousands of seed points to identify optimal streamline placement. RESULTS: The algorithm was assessed qualitatively on different left atrial models of fiber orientation with varying mesh resolutions (up to 375k triangles) and quantitatively by measuring streamline lengths and distribution of inter-streamline minimal distance. The complexity and the computational performance of the algorithm were studied as a function of streamline spacing in relation to triangular mesh resolution. CONCLUSION: More accurate geometrical computations, attention to details and fine-tuning led to an algorithm more amenable to applications that require precise positioning of streamlines.