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This study introduces an innovative real-time surgical planning platform optimized for the treatment of arterial aneurysms using intrasaccular flow disruption (IFD) devices. This platform incorporates a cutting-edge fast virtual deployment (FVD) algorithm alongside a discrete element method (DEM) for computational fluid dynamics (CFD) analyses. It facilitates the efficient virtual deployment of IFD devices, minimizing computational overhead while allowing for comprehensive postoperative hemodynamic efficacy assessment. The FVD algorithm employs an adaptive wall adherence and curvature control system, validated through both idealized and patient-specific model simulations. Post-treatment hemodynamic shifts are quantified by discretizing device wire filaments into discrete particles, which are then integrated with blood flow simulations for enhanced realism. The FVD algorithm efficiently executes virtual deployment of IFD devices within seconds, producing DEM-CFD computational models that align closely with bench testing, traditional Finite Element Method (FEM) analyses, and angiographic data. DEM-CFD outcomes link occlusion effectiveness to post-implantation hemodynamic characteristics, influenced by the aneurysm's unique anatomical features and clinical intervention strategies. The proposed platform demonstrates substantial improvement in balancing computational efficiency with analytical precision. It provides a viable and innovative framework for real-time surgical planning, presenting significant implications for clinical application in arterial aneurysm management., (© 2024 John Wiley & Sons Ltd.)

Reported in this paper is a cutting-edge computational investigation into the influence of geometric characteristics on abdominal aortic aneurysm (AAA) rupture risk, beyond the traditional measure of maximum aneurysm diameter. A Comprehensive fluid-structure interaction (FSI) analysis was employed to assess risk factors in a range of patient scenarios, with the use of three-dimensional (3D) AAA models reconstructed from patient-specific aortic data and finite element method. Wall shear stress (WSS), and its derivatives such as time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT) and transverse WSS (transWSS) offer insights into the force dynamics acting on the AAA wall. Emphasis is placed on these WSS-based metrics and seven key geometric indices. By correlating these geometric discrepancies with biomechanical phenomena, this study highlights the novel and profound impact of geometry on risk prediction. This study demonstrates the necessity of a multidimensional assessment approach, future efforts should complement these findings with experimental validations for an applicable approach for clinical use., (© 2024 John Wiley & Sons Ltd.)

The mechanisms leading to aneurysm occlusion after treatment with flow-diverting devices are not fully understood. Flow modification induces thrombus formation within the aneurysm cavity, but fibrin can simultaneously accumulate and cover the device scaffold, leading to further flow modification. However, the interplay and relative importance of these processes are not clearly understood. A computational model of fibrin accumulation and flow modification after flow diversion treatment of cerebral aneurysms has been developed under the guidance of in vitro experiments and observations. The model is based on the loose coupling of flow and transport-reaction equations that are solved separately by independent codes. Interaction or reactive terms account for thrombin production from prothrombin stimulated by thrombogenic metallic wires and inhibition by antithrombin as well as fibrin production from fibrinogen stimulated by thrombin and flow shear stress, and fibrin adhesion to device wires and already attached fibrin. The computational model was demonstrated and tested on idealized vessel and aneurysm geometries. The model was able to reproduce the salient features of fibrin accumulation after the deployment of flow-diverting devices in idealized in vitro models of cerebral aneurysms. Namely, fibrin production in regions of high shear stress, initial accumulation at the inflow zone, and progressive occlusion of the device and corresponding flow attenuation. The computational model linking flow dynamics to fibrin production, transport, and adhesion can be used to investigate and better understand the effects that lead to fibrin accumulation and the resulting aneurysm inflow reduction and intra-aneurysmal flow modulation., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Endovascular coil embolization is the primary therapeutic modality for intracranial aneurysms. Substantial reports have been found regarding the coil packing density and inflow jet. However, the hemodynamic effect of increasing the rate of tamponade in the inflow jet area within the aneurysm remains unclear. In this study, individualized geometries of six intracranial aneurysms were recruited: all six aneurysms were located in the internal carotid artery. Two groups were created by changing the position and orientation of the microcatheter for the release of the third segment of the filling coil. The finite element method was used to simulate coil deployment. Computational fluid dynamics was used to characterize hemodynamics in post-deployment aneurysms. The parameters evaluated included velocity reduction, wall shear stress (WSS), low WSS (LWSS), relative residence time (RRT), flow kinetic energy in the neck region of the aneurysms, and residual flow volume (RFV) in the aneurysms. At the peak time (t = 0.17 s), the targeted deployment group has similar proportion of LWSS area to conventional deployment groups: targeted 78.13% ± 34.59% versus normal 74.20% ± 36.94% (mean ± SD, p = 0.583). The targeted deployment group has a higher RRT area (targeted 16.84% ± 5.58% vs. normal 6.42% ± 5.67% [mean ± SD, p = 0.009]), smaller flow kinetic energy (targeted 9.43 ± 4.33 vs. normal 16.23 ± 5.92 [mean ± SD, p = 0.047]), and a larger RFV in the aneurysms (targeted 35.97 ± 24.35 mm 3 vs. normal 25.80 ± 18.94 mm 3 [mean ± SD, p = 0.44]). Inflow jets play an important role in the treatment of aneurysms, and deploying filling coils in accordance with inflow jets may result in a better hemodynamic environment., (© 2024 John Wiley & Sons Ltd.)

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging. Several influences, including wave reflections, fetal growth, vessel stiffness, and resistance distal to the vessel, contribute to these indices. Understanding these data is essential for making informed clinical decisions. Mathematical models can be used to investigate the relation between velocity profiles and physiological properties. This study presents a mathematical model designed to simulate velocity wave propagation throughout the fetal cardiovascular system, facilitating the assessment of factors influencing velocity-based indices. The model combines a one-fiber model of the heart with a 1D wave propagation model describing the larger vessels of the circulatory system and a lumped parameter model for the microcirculation. Fetal growth from 20 to 40 weeks of gestational age is incorporated by adjusting cardiac and circulatory parameter settings according to scaling laws. The model's results, including cardiac function, cardiac output distribution, and volume distribution, show a good agreement with literature studies for a growing healthy fetus from 20 to 40 weeks. In addition, Doppler indices are simulated in various vessels and agree with literature as well. In conclusion, this study introduces a novel closed-loop 0D-1D mathematical model that has been verified against literature studies. This model offers a valuable platform for analyzing factors influencing velocity-based indices in the fetal cardiovascular system., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The Windkessel (WK) model is a simplified mathematical model used to represent the systemic arterial circulation. While the WK model is useful for studying blood flow dynamics, it suffers from inaccuracies or uncertainties that should be considered when using it to make physiological predictions. This paper aims to develop an efficient and easy-to-implement uncertainty quantification method based on a local gradient-based formulation to quantify the uncertainty of the pressure waveform resulting from aleatory uncertainties of the WK parameters and flow waveform. The proposed methodology, tested against Monte Carlo simulations, demonstrates good agreement in estimating blood pressure uncertainties due to uncertain Windkessel parameters, but less agreement considering uncertain blood-flow waveforms. To illustrate our methodology's applicability, we assessed the aortic pressure uncertainty generated by Windkessel parameters-sets from an available in silico database representing healthy adults. The results from the proposed formulation align qualitatively with those in the database and in vivo data. Furthermore, we investigated how changes in the uncertainty of the Windkessel parameters affect the uncertainty of systolic, diastolic, and pulse pressures. We found that peripheral resistance uncertainty produces the most significant change in the systolic and diastolic blood pressure uncertainties. On the other hand, compliance uncertainty considerably modifies the pulse pressure standard deviation. The presented expansion-based method is a tool for efficiently propagating the Windkessel parameters' uncertainty to the pressure waveform. The Windkessel model's clinical use depends on the reliability of the pressure in the presence of input uncertainties, which can be efficiently investigated with the proposed methodology. For instance, in wearable technology that uses sensor data and the Windkessel model to estimate systolic and diastolic blood pressures, it is important to check the confidence level in these calculations to ensure that the pressures accurately reflect the patient's cardiovascular condition., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

In the last decades, many computational models have been developed to predict soft tissue growth and remodeling (G&R). The constrained mixture theory describes fundamental mechanobiological processes in soft tissue G&R and has been widely adopted in cardiovascular models of G&R. However, even after two decades of work, large organ-scale models are rare, mainly due to high computational costs (model evaluation and memory consumption), especially in long-range simulations. We propose two strategies to adaptively integrate history variables in constrained mixture models to enable large organ-scale simulations of G&R. Both strategies exploit that the influence of deposited tissue on the current mixture decreases over time through degradation. One strategy is independent of external loading, allowing the estimation of the computational resources ahead of the simulation. The other adapts the history snapshots based on the local mechanobiological environment so that the additional integration errors can be controlled and kept negligibly small, even in G&R scenarios with severe perturbations. We analyze the adaptively integrated constrained mixture model on a tissue patch for a parameter study and show the performance under different G&R scenarios. To confirm that adaptive strategies enable large organ-scale examples, we show simulations of different hypertension conditions with a real-world example of a biventricular heart discretized with a finite element mesh. In our example, adaptive integrations sped up simulations by a factor of three and reduced memory requirements to one-sixth. The reduction of the computational costs gets even more pronounced for simulations over longer periods. Adaptive integration of the history variables allows studying more finely resolved models and longer G&R periods while computational costs are drastically reduced and largely constant in time., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The opening and closing dynamics of the aortic valve (AV) has a strong influence on haemodynamics in the aortic root, and both play a pivotal role in maintaining normal physiological functions of the valve. The aim of this study was to establish a subject-specific fluid-structure interaction (FSI) workflow capable of simulating the motion of a tricuspid healthy valve and the surrounding haemodynamics under physiologically realistic conditions. A subject-specific aortic root was reconstructed from magnetic resonance (MR) images acquired from a healthy volunteer, whilst the valve leaflets were built using a parametric model fitted to the subject-specific aortic root geometry. The material behaviour of the leaflets was described using the isotropic hyperelastic Ogden model, and subject-specific boundary conditions were derived from 4D-flow MR imaging (4D-MRI). Strongly coupled FSI simulations were performed using a finite volume-based boundary conforming method implemented in FlowVision. Our FSI model was able to simulate the opening and closing of the AV throughout the entire cardiac cycle. Comparisons of simulation results with 4D-MRI showed a good agreement in key haemodynamic parameters, with stroke volume differing by 7.5% and the maximum jet velocity differing by less than 1%. Detailed analysis of wall shear stress (WSS) on the leaflets revealed much higher WSS on the ventricular side than the aortic side and different spatial patterns amongst the three leaflets., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The article presents a semi-automatic approach to generating structured hexahedral meshes of patient-specific aortas ailed by aortic dissection. The condition manifests itself as a formation of two blood flow channels in the aorta, as a result of a tear in the inner layers of the aortic wall. Subsequently, the morphology of the aorta is greatly impacted, making the task of domain discretization highly challenging. The meshing algorithm presented herein is automatic for the individual lumina, whereas the tears require user interaction. Starting from an input (triangle) surface mesh, we construct an implicit surface representation as well as a topological skeleton, which provides a basis for the generation of a block-structure. Thereafter, the mesh generation is performed via transfinite maps. The meshes are structured and fully hexahedral, exhibit good quality and reliably match the original surface. As they are generated with computational fluid dynamics in mind, a fluid flow simulation is performed to verify their usefulness. Moreover, since the approach is based on valid block-structures, the meshes can be made very coarse (around 1000 elements for an entire aortic dissection domain), and thus promote using solvers based on the geometric multigrid method, which is typically reliant on the presence of a hierarchy of coarser meshes., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Autologous arteriovenous fistula (AVF) is a commonly used vascular access (VA) for hemodialysis, and hemodynamic changes are one of the main factors for its failure. To explore the effect of geometry on the hemodynamics in the AVF, a modified model is built with a gradual and smooth turn at the anastomosis and is compared with the traditional model, which has an abrupt sharp turn at the anastomisis. Transient computational fluid dynamics (CFD) simulations were performed for the comparison and analysis of the hemodynamic fields of the two models at different stages of the pulse cycle. The results showed that the low shear stress region and high oscillatory shear stress region in the modified AVF model coincided with regions of intimal hyperplasia that have been identified by previous studies. A comparison with the blood flow velocities measured in vivo was performed, and the error between the simulation results and the medical data was reduced by 22% in the modified model, which verifies the rationality and utility of the modified model., (© 2024 John Wiley & Sons Ltd.)

Reduced order modelling (ROMs) methods, such as proper orthogonal decomposition (POD), systematically reduce the dimensionality of high-fidelity computational models and potentially achieve large gains in execution speed. Machine learning (ML) using neural networks has been used to overcome limitations of traditional ROM techniques when applied to nonlinear problems, which has led to the recent development of reduced order models augmented by machine learning (ML-ROMs). However, the performance of ML-ROMs is yet to be widely evaluated in realistic applications and questions remain regarding the optimal design of ML-ROMs. In this study, we investigate the application of a non-intrusive parametric ML-ROM to a nonlinear, time-dependent fluid dynamics problem in a complex 3D geometry. We construct the ML-ROM using POD for dimensionality reduction and neural networks for interpolation of the ROM coefficients. We compare three different network designs in terms of approximation accuracy and performance. We test our ML-ROM on a flow problem in intracranial aneurysms, where flow variability effects are important when evaluating rupture risk and simulating treatment outcomes. The best-performing network design in our comparison used a two-stage POD reduction, a technique rarely used in previous studies. The best-performing ROM achieved mean test accuracies of 98.6% and 97.6% in the parent vessel and the aneurysm, respectively, while providing speed-up factors of the order 10 5 ., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The effectiveness of various stroke treatments depends on the anatomical variability of the cerebral vasculature, particularly the collateral blood vessel network. Collaterals at the level of the Circle of Willis and distal collaterals, such as the leptomeningeal arteries, serve as alternative avenues of flow when the primary pathway is obstructed during an ischemic stroke. Stroke treatment typically involves catheterization of the primary pathway, and the potential risk of further flow reduction to the affected brain area during this treatment has not been previously investigated. To address this clinical question, we derived the lumped parameters for catheterized blood vessels and implemented a corresponding distributed compartment (0D) model. This 0D model was validated against an experimental model and benchmark test cases solved using a 1D model. Additionally, we compared various off-center catheter trajectories modeled using a 3D solver to this 0D model. The differences between them were minimal, validating the simplifying assumption of the central catheter placement in the 0D model. The 0D model was then used to simulate blood flows in realistic cerebral arterial networks with different collateralization characteristics. Ischemic strokes were modeled by occlusion of the M1 segment of the middle cerebral artery in these networks. Catheters of different diameters were inserted up to the obstructed segment and flow alterations in the network were calculated. Results showed up to 45% maximum blood flow reduction in the affected brain region. These findings suggest that catheterization during stroke treatment may have a further detrimental effect for some patients with poor collateralization., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

In this work, we couple a lumped-parameter closed-loop model of the cardiovascular system with a physiologically-detailed mathematical description of the baroreflex afferent pathway. The model features a classical Hodgkin-Huxley current-type model for the baroreflex afferent limb (primary neuron) and for the second-order neuron in the central nervous system. The pulsatile arterial wall distension triggers a frequency-modulated sequence of action potentials at the afferent neuron. This signal is then integrated at the brainstem neuron model. The efferent limb, representing the sympathetic and parasympathetic nervous system, is described as a transfer function acting on heart and blood vessel model parameters in order to control arterial pressure. Three in silico experiments are shown here: a step increase in the aortic pressure to evaluate the functionality of the reflex arch, a hemorrhagic episode and an infusion simulation. Through this model, it is possible to study the biophysical dynamics of the ionic currents proposed for the afferent limb components of the baroreflex during the cardiac cycle, and the way in which currents dynamics affect the cardiovascular function. Moreover, this system can be further developed to study in detail each baroreflex loop component, helping to unveil the mechanisms involved in the cardiovascular afferent information processing., (© 2024 John Wiley & Sons Ltd.)

Computational fluid dynamics (CFD) simulations have shown great potentials in cardiovascular disease diagnosis and postoperative assessment. Patient-specific and well-tuned boundary conditions are key to obtaining accurate and reliable hemodynamic results. However, CFD simulations are usually performed under non-patient-specific flow conditions due to the absence of in vivo flow and pressure measurements. This study proposes a new method to overcome this challenge by tuning inlet boundary conditions using data extracted from electrocardiogram (ECG). Five patient-specific geometric models of type B aortic dissection were reconstructed from computed tomography (CT) images. Other available data included stoke volume (SV), ECG, and 4D-flow magnetic resonance imaging (MRI). ECG waveforms were processed to extract patient-specific systole to diastole ratio (SDR). Inlet boundary conditions were defined based on a generic aortic flow waveform tuned using (1) SV only, and (2) with ECG and SV (ECG + SV). 4D-flow MRI derived inlet boundary conditions were also used in patient-specific simulations to provide the gold standard for comparison and validation. Simulations using inlet flow waveform tuned with ECG + SV not only successfully reproduced flow distributions in the descending aorta but also provided accurate prediction of time-averaged wall shear stress (TAWSS) in the primary entry tear (PET) and abdominal regions, as well as maximum pressure difference, ∆P max , from the aortic root to the distal false lumen. Compared with simulations with inlet waveform tuned with SV alone, using ECG + SV in the tuning method significantly reduced the error in false lumen ejection fraction at the PET (from 149.1% to 6.2%), reduced errors in TAWSS at the PET (from 54.1% to 5.7%) and in the abdominal region (from 61.3% to 11.1%), and improved ∆P max prediction (from 283.1% to 18.8%) However, neither of these inlet waveforms could be used for accurate prediction of TAWSS in the ascending aorta. This study demonstrates the importance of SDR in tailoring inlet flow waveforms for patient-specific hemodynamic simulations. A well-tuned flow waveform is essential for ensuring that the simulation results are patient-specific, thereby enhancing the confidence and fidelity of computational tools in future clinical applications., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Pulmonary valve replacement (PVR) consists of substituting a patient's original valve with a prosthetic one, primarily addressing pulmonary valve insufficiency, which is crucially relevant in Tetralogy of Fallot repairment. While extensive clinical and computational literature on aortic and mitral valve replacements is available, PVR's post-procedural haemodynamics in the pulmonary artery and the impact of prosthetic valve dynamics remain significantly understudied. Addressing this gap, we introduce a reduced Fluid-Structure Interaction (rFSI) model, applied for the first time to the pulmonary valve. This model couples a three-dimensional computational representation of pulmonary artery haemodynamics with a one-degree-of-freedom model to account for valve structural mechanics. Through this approach, we analyse patient-specific haemodynamics pre and post PVR. Patient-specific geometries, reconstructed from CT scans, are virtually equipped with a template valve geometry. Boundary conditions for the model are established using a lumped-parameter model, fine-tuned based on clinical patient data. Our model accurately reproduces patient-specific haemodynamic changes across different scenarios: pre-PVR, six months post-PVR, and a follow-up condition after a decade. It effectively demonstrates the impact of valve implantation on sustaining the diastolic pressure gradient across the valve. The numerical results indicate that our valve model is able to reproduce overall physiological and/or pathological conditions, as preliminary assessed on two different patients. This promising approach provides insights into post-PVR haemodynamics and prosthetic valve effects, shedding light on potential implications for patient-specific outcomes., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Computational models of the cardiovascular system are increasingly used for the diagnosis, treatment, and prevention of cardiovascular disease. Before being used for translational applications, the predictive abilities of these models need to be thoroughly demonstrated through verification, validation, and uncertainty quantification. When results depend on multiple uncertain inputs, sensitivity analysis is typically the first step required to separate relevant from unimportant inputs, and is key to determine an initial reduction on the problem dimensionality that will significantly affect the cost of all downstream analysis tasks. For computationally expensive models with numerous uncertain inputs, sample-based sensitivity analysis may become impractical due to the substantial number of model evaluations it typically necessitates. To overcome this limitation, we consider recently proposed Multifidelity Monte Carlo estimators for Sobol' sensitivity indices, and demonstrate their applicability to an idealized model of the common carotid artery. Variance reduction is achieved combining a small number of three-dimensional fluid-structure interaction simulations with affordable one- and zero-dimensional reduced-order models. These multifidelity Monte Carlo estimators are compared with traditional Monte Carlo and polynomial chaos expansion estimates. Specifically, we show consistent sensitivity ranks for both bi- (1D/0D) and tri-fidelity (3D/1D/0D) estimators, and superior variance reduction compared to traditional single-fidelity Monte Carlo estimators for the same computational budget. As the computational burden of Monte Carlo estimators for Sobol' indices is significantly affected by the problem dimensionality, polynomial chaos expansion is found to have lower computational cost for idealized models with smooth stochastic response., (© 2024 John Wiley & Sons Ltd.)

An epicardial approach is often used in radiofrequency (RF) catheter ablation to ablate ventricular tachycardia when an endocardial approach fails. Our objective was to analyze the effect of the position of the dispersive patch (DP) on lesion size using computer modeling during epicardial approach. We compared the posterior position (patient's back), commonly used in clinical practice, to the anterior position (patient's chest). The model considered ventricular wall thicknesses between 4 and 8 mm, and electrode insertion depths between .3 and .7 mm. RF pulses were simulated with 20 W of power for 30 s duration. Statistically significant differences (P < .001) were found between both DP positions in terms of baseline impedance, RF current (at 15 s) and thermal lesion size. The anterior position involved lower impedance (130.8 ± 4.7 vs. 146.2 ± 4.9 Ω) and a higher current (401.5 ± 5.6 vs. 377.5 ± 5.1 mA). The anterior position created lesion sizes larger than the posterior position: 8.9 ± 0.4 vs. 8.4 ± 0.4 mm in maximum width, 8.6 ± 0.4 vs. 8.1 ± 0.4 mm in surface width, and 4.5 ± 0.4 vs. 4.3 ± 0.4 mm in depth. Our results suggest that: (1) the redirection of the RF currents due to repositioning the PD has little impact on lesion size and only affects baseline impedance, and (2) the differences in lesion size are only 0.5 mm wider and 0.2 mm deeper for the anterior position, which does not seem to have a clinical impact in the context of VT ablation., (© 2024 John Wiley & Sons Ltd.)

The aortic valve (AV) is crucial for cardiovascular (CV) hemodynamic, impacting cardiac output (CO) and left ventricular volumetric flow rate (LVQ). Its nonlinear behavior challenges standard LVQ prediction methods as well as CO one. This study presents a novel approach for modeling the AV in the CV system, offering an improved method for estimating crucial parameters like LVQ across various AV conditions, including aortic stenosis (AS). The model, based on AV channel length during the entire cardiac phase, introduces a time-varying AV resistance (TV-AVR) parameterized by the pressure ratio across the AV and LVQ, enabling the simulation of both healthy and AS-related conditions. To validate this model, in vitro measurements are compared using a hybrid mock circulatory loop device. An unconventional use of a convolutional neural network (CNN) corrects the model's estimates, eliminating the need for labeled datasets. This approach, incorporating real-time learning and transforming 1-D CV signals into 2-D tensors, significantly improves the accuracy of LVQ measurements, achieving an error rate of less than 3.41 ± 4.84% for CO in healthy conditions and 2.83 ± 1.35% in AS cases-a 33.13% enhancement over linear diode models. These results underscore the potential of this approach for enhancing the diagnosis, prediction, and treatment of AV diseases. The key contributions of the proposed method encompass nonlinear TV-AVR estimation, investigation of transient CV responses, prediction of instantaneous CO, development of a flexible framework for noninvasive measurements integration, and the introduction of an adjustable resistance model using an extended Kalman filter (EKF) and CNN combination, all without requiring labeled data., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

We present a 3D discrete-continuum model to simulate blood pressure in large microvascular tissues in the absence of known capillary network architecture. Our hybrid approach combines a 1D Poiseuille flow description for large, discrete arteriolar and venular networks coupled to a continuum-based Darcy model, point sources of flux, for transport in the capillary bed. We evaluate our hybrid approach using a vascular network imaged from the mouse brain medulla/pons using multi-fluorescence high-resolution episcopic microscopy (MF-HREM). We use the fully-resolved vascular network to predict the hydraulic conductivity of the capillary network and generate a fully-discrete pressure solution to benchmark against. Our results demonstrate that the discrete-continuum methodology is a computationally feasible and effective tool for predicting blood pressure in real-world microvascular tissues when capillary microvessels are poorly defined., (© 2024 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation., (© 2024 The Author(s). International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

A mathematical model of myocardial perfusion based on the lattice Boltzmann method (LBM) is proposed and its applicability is investigated in both healthy and diseased cases. The myocardium is conceptualized as a porous material in which the transport and mass transfer of a contrast agent in blood flow is studied. The results of myocardial perfusion obtained using LBM in 1D and 2D are confronted with previously reported results in the literature and the results obtained using the mixed-hybrid finite element method. Since LBM is not suitable for simulating flow in heterogeneous porous media, a simplified and computationally efficient 1D-analog approach to 2D diseased case is proposed and its applicability discussed., (© 2024 John Wiley & Sons Ltd.)

Strokes are one of the leading causes of death in the United States. Stroke treatment involves removal or dissolution of the obstruction (usually a clot) in the blocked artery by catheter insertion. A computer simulation to systematically plan such patient-specific treatments needs a network of about 10 5 blood vessels including collaterals. The existing computational fluid dynamic (CFD) solvers are not employed for stroke treatment planning as they are incapable of providing solutions for such big arterial trees in a reasonable amount of time. This work presents a novel one-dimensional mathematical formulation for blood flow modeling in an elastic blood vessel with a centrally placed rigid catheter. The governing equations are first-order hyperbolic partial differential equations, and the hypergeometric function needs to be computed to obtain the characteristic system of these hyperbolic equations. We employed the Discontinuous Galerkin method to solve the hyperbolic system and validated the implementation by comparing it against a well-established 3D CFD solver using idealized vessels and a realistic truncated arterial network. The results showed clinically insignificant differences in steady flow cases, with overall variations between 1D and 3D models remaining below 10%. Additionally, the solver accurately captured wave reflection phenomena at domain discontinuities in unsteady cases. A primary advantage of this model over 3D solvers is its ease in obtaining a discretized geometry of complex vasculatures with multiple arterial branches. Thus, the 1D computational model offers good accuracy and applicability in simulating complex vasculatures, demonstrating promising potential for investigating patient-specific endovascular interventions in strokes., (© 2024 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Background and Purpose: Balloon test occlusion (BTO) evaluates cerebral ischemic tolerance before internal carotid artery (ICA) sacrifice but carries risks like dissection and thrombosis. This study introduces a new approach using a patient-specific circle of Willis (COW) blood flow model, based on non-invasive quantitative MR angiography (qMRA) measurements, to predict the outcomes of BTO., Methods: We developed individualized COW blood flow models for 43 patients undergoing BTO. These models simulated blood flow and pressure under normal conditions and with the ICA occlusion. We then compared the model's predictions of blood flow changes due to the simulated ICA occlusion to actual qMRA measurements before the BTO., Results: For all 31 BTO failures, the ipsilateral hemisphere showed an average flow decrease of 15 ± 10% (mean ± standard deviation), compared to 3 ± 2% in the contralateral hemisphere. In all 12 BTO passes, these figures were 6 ± 3% and 1 ± 0.8%, respectively. Notably, all BTO passes had less than a 10% reduction in the ipsilateral hemisphere. In contrast, 65% of BTO failures and 67% single-photon emission computed tomography (SPECT) failures exhibited a decrease of 10% or more in the same region., Conclusion: Blood flow reduction exceeding 10% in the ipsilateral hemisphere during BTO is a strong predictor of failure in both BTO and SPECT. Our patient-specific COW blood flow models, incorporating detailed flow and arterial geometry data, offered valuable insights for predicting BTO outcomes. These models are especially beneficial for situations where conducting BTO or SPECT is clinically impractical., (© 2024 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

As living standards rise, more and more people are paying attention to their own health, especially issues such as cerebral thrombosis, cerebral infarction, and other cerebral blood flow problems. An accurate simulation of blood flow within cerebral vessels has emerged as a crucial area of research. In this study, we focus on microcirculatory blood flow in ischemic brain tissue and employ a 0D-1D geometric multi-scale coupled model to characterize this process. Given the intricate nature of human cerebral vessels, we apply a numerical method combining the finite element method and the third-order Runge-Kutta method to resolve the coupled model. To enhance computational efficiency, we introduce a fast method based on the reduced-order extrapolation algorithm. Our numerical example underscores the stability of the method and convergence accuracy to O h 3 + τ 3 , while significantly improving the accuracy and efficiency of blood flow simulation, making the mechanism analysis more accurate. Additionally, we present examples detailing variations and distribution of intracranial pressure and blood flow in ischemic brain tissue throughout a cardiac cycle. Both reduced vascular compliance and vascular stenosis can have adverse effects on intracranial cerebral pressure and blood flow, leading to insufficient local oxygen supply and negative effects on brain function. Meanwhile, there will also be corresponding changes in volume flow and pulsatile blood pressure., (© 2024 John Wiley & Sons Ltd.)

We examined the effect of minimal lumen segmentation uncertainty on Fractional Flow Reserve obtained from Coronary Computed Tomography Angiography FFR CT . A total of 14 patient-specific coronary models with different stenosis locations and degrees of severity were enrolled in this study. The optimal segmented coronary lumens were disturbed using intra ± 6 % and inter-operator ± 15 % variations on the segmentation threshold. FFR CT was evaluated in each case by 3D-OD CFD simulations. The findings suggest that the sensitivity of FFR CT to this type of uncertainty increases distally and with the stenosis severity. Cases with moderate or severe distal coronary lesions should undergo either exact and thorough segmentation operations or invasive FFR measurements, particularly if the FFR CT is close to the cutoff (0.80). Therefore, we conclude that it is crucial to consider the lesion's location and degree of severity when evaluating FFR CT results., (© 2024 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Atrial fibrillation (AF) poses a significant risk of stroke due to thrombus formation, which primarily occurs in the left atrial appendage (LAA). Medical image-based computational fluid dynamics (CFD) simulations can provide valuable insight into patient-specific hemodynamics and could potentially enhance personalized assessment of thrombus risk. However, the importance of accurately representing the left atrial (LA) wall dynamics has not been fully resolved. In this study, we compared four modeling scenarios; rigid walls, a generic wall motion based on a reference motion, a semi-generic wall motion based on patient-specific motion, and patient-specific wall motion based on medical images. We considered a LA geometry acquired from 4D computed tomography during AF, systematically performed convergence tests to assess the numerical accuracy of our solution strategy, and quantified the differences between the four approaches. The results revealed that wall motion had no discernible impact on LA cavity hemodynamics, nor on the markers that indicate thrombus formation. However, the flow patterns within the LAA deviated significantly in the rigid model, indicating that the assumption of rigid walls may lead to errors in the estimated risk factors. In contrast, the generic, semi-generic, and patient-specific cases were qualitatively similar. The results highlight the crucial role of wall motion on hemodynamics and predictors of thrombus formation, and also demonstrate the potential of using a generic motion model as a surrogate for the more complex patient-specific motion. While the present study considered a single case, the employed CFD framework is entirely open-source and designed for adaptability, allowing for integration of additional models and generic motions., (© 2024 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention., (© 2024 John Wiley & Sons Ltd.)

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample-based approach. We propose a new offline-online pipeline for probabilistic real-time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero-dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository., (© 2024 John Wiley & Sons Ltd.)

The dialysis catheter indwelling in human bodies has a high risk of inducing thrombus and stenosis. Biomechanical research showed that such physiological complications are triggered by the wall shear stress of the vascular vessel. This study aimed to assess the impact of CVC implantation on central venous haemodynamics and the potential alterations in the haemodynamic environment related to thrombus development. The SVC structure was built from the images from computed tomography. The blood flow was calculated using the Carreau model, and the fluid domain was determined by CFD. The vascular wall and the CVC were computed using FEA. The elastic interaction between the vessel wall and the flow field was considered using FSI simulation. With consideration of the effect of coupling, it was shown that the catheter vibrated in the vascular systems due to the periodic variation of blood pressure, with an amplitude of up to 10% of the vessel width. Spiral flow was observed along the catheter after CVC indwelling, and recirculation flow appeared near the catheter tip. High OSI and WSS regions occurred at the catheter tip and the vascular junction. The arterial lumen tip had a larger effect on the WSS and OSI values on the vascular wall. Considering FSI simulation, the movement of the catheter inside the blood flow was simulated in the deformable vessel. After CVC indwelling, spiral flow and recirculation flow were observed near the regions with high WSS and OSI values., (© 2024 John Wiley & Sons Ltd.)

The study aimed to investigate the mechanical factors for distal stent graft-induced new entry (dSINE) in aortic dissection patients and discussed these factors in conjunction with aortic morphology. Two patients (one dSINE and one non-dSINE), with the same age, gender, and type of implanted stent, were selected, then aortic morphological parameters were calculated. In addition, the stent material parameters used by the patients were also fitted. Simulations were performed based on the patient's aortic model and the stent graft used. The true lumen segment at the distal stent graft was designated as the "dSINE risk zone," and mechanical parameters (maximum principal strain, maximum principal stress) were computed. When approaching the area with higher mechanical parameters in the dSINE risk zone, dSINE patient exhibited higher values and growth rates in mechanical parameters compared to non-dSINE patient. Furthermore, dSINE patient also presented larger aortic taper ratio, stent oversizing ratio, and expansion mismatch ratio of the distal true lumen (EMRDTR). The larger mechanical parameters and growth rates in dSINE patient corresponded to a greater aortic taper ratio, stent oversizing ratio, and EMRDTR. The failure of dSINE prediction by the stent tortuosity index indicated that mechanical parameters were the fundamental reasons for dSINE development., (© 2024 John Wiley & Sons Ltd.)

The deformability of blood vessels in one-dimensional blood flow models is typically described through a pressure-area relation, known as the tube law. The most used tube laws take into account the elastic and viscous components of the tension of the vessel wall. Accurately parametrizing the tube laws is vital for replicating pressure and flow wave propagation phenomena. Here, we present a novel mathematical-property-preserving approach for the estimation of the parameters of the elastic and viscoelastic tube laws. Our goal was to estimate the parameters by using ovine and human in vitro data, while constraining them to meet prescribed mathematical properties. Results show that both elastic and viscoelastic tube laws accurately describe experimental pressure-area data concerning both quantitative and qualitative aspects. Additionally, the viscoelastic tube law can provide a qualitative explanation for the observed hysteresis cycles. The two models were evaluated using two approaches: (i) allowing all parameters to freely vary within their respective ranges and (ii) fixing some of the parameters. The former approach was found to be the most suitable for reproducing pressure-area curves., (© 2024 John Wiley & Sons Ltd.)

Valvular heart diseases (such as stenosis and regurgitation) are recognized as a rapidly growing cause of global deaths and major contributors to disability. The most effective treatment for these pathologies is the replacement of the natural valve with a prosthetic one. Our work considers an innovative design for prosthetic aortic valves that combines the reliability and durability of artificial valves with the flexibility of tissue valves. It consists of a rigid support and three polymer leaflets which can be cut from an extruded flat sheet, and is referred to hereafter as the Wheatley aortic valve (WAV). As a first step towards the understanding of the mechanical behavior of the WAV, we report here on the implementation of a numerical model built with the ICFD multi-physics solver of the LS-DYNA software. The model is calibrated and validated using data from a basic pulsatile-flow experiment in a water-filled straight tube. Sensitivity to model parameters (contact parameters, mesh size, etc.) and to design parameters (height, material constants) is studied. The numerical data allow us to describe the leaflet motion and the liquid flow in great detail, and to investigate the possible failure modes in cases of unfavorable operational conditions (in particular, if the leaflet height is inadequate). In future work the numerical model developed here will be used to assess the thrombogenic properties of the valve under physiological conditions., (© 2023 John Wiley & Sons Ltd.)

The study was carried out to investigate the effect of the artery with different pulse values and stenosis rates on the pressure drop, the peristaltic pump outlet pressure, fractional flow reserve (FFR) and most importantly the amount of power consumed by the peristaltic pump. For this purpose, images taken from the clinical environment were produced as models (10 mm inlet diameter) with 0% and 70% percent areal stenosis rates (PSR) on a three-dimensional (3D) printer. In the experimental system, pure water was used as the fluid at 54, 84, 114, 132, and 168 bpm pulse values. In addition, computational fluid dynamics (CFD) analyzes of the test region were performed using experimental boundary conditions with the help of ANSYS-Fluent software. The findings showed that as PSR increases in the arteries, the pressure drop in the stenosis region increases and this amount increases dramatically with increasing effort. An increase of approximately 40% was observed in the pump outlet pressure value from 54 bpm to 168 bpm in the PSR 0% model and 51% increase in the PSR 70% model. It has been observed that the pump does more work to overcome the increased pressure difference due to increased pulse rate and PSR. With the effect of contraction, the power consumption of the pump increased from 9.2% for 54 bpm to 13.8% for 168 bpm. In both models, the Wall Shear Stress (WSS) increased significantly. WSS increased abruptly in the stenosis and arcuate regions, while sudden decreases were observed in the flow separation region., (© 2023 John Wiley & Sons Ltd.)

A major challenge in the computational fluid dynamics modeling of the heart function is the simulation of isovolumetric phases when the hemodynamics problem is driven by a prescribed boundary displacement. During such phases, both atrioventricular and semilunar valves are closed: consequently, the ventricular pressure may not be uniquely defined, and spurious oscillations may arise in numerical simulations. These oscillations can strongly affect valve dynamics models driven by the blood flow, making unlikely to recovering physiological dynamics. Hence, prescribed opening and closing times are usually employed, or the isovolumetric phases are neglected altogether. In this article, we propose a suitable modification of the Resistive Immersed Implicit Surface (RIIS) method (Fedele et al., Biomech Model Mechanobiol 2017, 16, 1779-1803) by introducing a reaction term to correctly capture the pressure transients during isovolumetric phases. The method, that we call Augmented RIIS (ARIIS) method, extends the previously proposed ARIS method (This et al., Int J Numer Methods Biomed Eng 2020, 36, e3223) to the case of a mesh which is not body-fitted to the valves. We test the proposed method on two different benchmark problems, including a new simplified problem that retains all the characteristics of a heart cycle. We apply the ARIIS method to a fluid dynamics simulation of a realistic left heart geometry, and we show that ARIIS allows to correctly simulate isovolumetric phases, differently from standard RIIS method. Finally, we demonstrate that by the new method the cardiac valves can open and close without prescribing any opening/closing times., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The effect of mechano-electrical feedback on re-entry formation and maintenance was studied using a model of myocardial electromechanics that accounts for two components of myocardial conductivity and delayed strain-dependent changes in membrane capacitance that causes a conduction slowing. Two scenarios were simulated in 2D numerical experiments: (i) propagation of an excitation-contraction wave beyond the edge of a nonconductive nonexcitable obstacle; (ii) circulation of a re-entry wave around a nonconductive nonexcitable obstacle. The simulations demonstrated that the delayed strain-dependent deceleration of the conduction waves promotes the detachment of the excitation-contraction waves from the sharp edge of an elongated obstacle and modulates the re-entry waves rotating around a compact obstacle. The data show that the mechano-electrical feedback, together with an increase in the stimulation frequency and an increase in the excitation threshold, is an arrhythmogenic factor that must be taken into account when analyzing the possibility of the re-entry formation., (© 2022 John Wiley & Sons Ltd.)

When modeling complex fluid networks using one-dimensional (1D) approaches, boundary conditions can be imposed using zero-dimensional (0D) models. An application case is the modeling of the entire human circulation using closed-loop models. These models can be considered as a tool to investigate short-term transient and stationary hemodynamic responses to postural changes. The first shortcoming of existing 1D modeling methods in simulating these sudden maneuvers is their inability to deal with rapid variations in flow conditions, as they are limited to the subsonic case. On the other hand, numerical modeling of 0D models representing microvascular beds, venous valves or heart chambers is also currently modeled assuming subsonic flow conditions in 1D connecting vessels, failing when transonic and supersonic flow conditions appear. Therefore, if numerical simulation of sudden maneuvers is a goal in closed-loop models, it is necessary to reformulate the current methodologies used when coupling 0D and 1D models, allowing the correct handling of flow evolution for both subsonic and transonic conditions. This work focuses on the extension of the general methodology for the Junction Riemann Problem (JRP) when coupling 0D and 1D models. As an example of application, the short-term transient response to head-up tilt (HUT) from supine to upright position of a closed-loop model is shown, demonstrating the potential, capability and necessity of the presented numerical models when dealing with sudden maneuvers., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Blood flow within the left ventricle provides important information regarding cardiac function in health and disease. The mitral valve strongly influences the formation of flow structures and there exist various approaches for the representation of the valve in numerical models of left ventricular blood flow. However, a systematic comparison of the various mitral valve models is missing, making a priori decisions considering the overall model's context of use impossible. Within this study, a benchmark setup to compare the influence of mitral valve modeling strategies on intraventricular flow features was developed. Then, five mitral valve models of increasing complexity: no modeling, static wall, 2D and 3D porous medium with time-dependent porosity, and one-way fluid-structure interaction (FSI) were compared with each other. The flow features velocity, kinetic energy, transmitral pressure drop, vortex formation, flow asymmetry as well as computational cost and ease-of-implementation were evaluated. The one-way FSI approach provides the highest level of flow detail, which is accompanied by the highest numerical costs and challenges with the implementation. As an alternative, the porous medium approach with the expansion including time-dependent porosity provides good results with up to 10% deviations in the flow features (except the transmitral pressure drop) in comparison to the FSI model and only a fraction (11%) of numerical costs. However, jet propagation speed is highly underestimated by all alternative approaches to the FSI model. Taken together, our benchmark setup allows a quantitative comparison of various mitral valve modeling approaches and is provided to the scientific community for further testing and expansion., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Biomechanical modeling and simulation is expected to play a significant role in the development of the next generation tools in many fields of medicine. However, full-order finite element models of complex organs such as the heart can be computationally very expensive, thus limiting their practical usability. Therefore, reduced models are much valuable to be used, for example, for pre-calibration of full-order models, fast predictions, real-time applications, and so forth. In this work, focused on the left ventricle, we develop a reduced model by defining reduced geometry & kinematics while keeping general motion and behavior laws, allowing to derive a reduced model where all variables & parameters have a strong physical meaning. More specifically, we propose a reduced ventricular model based on cylindrical geometry & kinematics, which allows to describe the myofiber orientation through the ventricular wall and to represent contraction patterns such as ventricular twist, two important features of ventricular mechanics. Our model is based on the original cylindrical model of Guccione, McCulloch, & Waldman (1991); Guccione, Waldman, & McCulloch (1993), albeit with multiple differences: we propose a fully dynamical formulation, integrated into an open-loop lumped circulation model, and based on a material behavior that incorporates a fine description of contraction mechanisms; moreover, the issue of the cylinder closure has been completely reformulated; our numerical approach is novel aswell, with consistent spatial (finite element) and time discretizations. Finally, we analyze the sensitivity of the model response to various numerical and physical parameters, and study its physiological response., (© 2023 John Wiley & Sons Ltd.)

Prosthetic polymeric heart valves (PHVs) have the potential to overcome the inherent material and design limitations of traditional valves in the treatment of valvular heart disease; however, their durability remains limited. Optimal design of the valve structure is necessary to improve their durability. This study aimed to enhance the fatigue resistance of PHVs by improving the stress distribution. Iterative subregional thickening of the leaflets was used, and the mechanical stress distribution and hemodynamics of these polymeric tri-leaflet valves were characterized using a fluid-structure interaction approach. Subregional thickening led to a reduction in stress concentration on the leaflet, with the effective orifice area still meeting ISO 5840-3 and the regurgitant volume achieving a similar value to those in previous studies. The maximum stress in the final iteration was reduced by 28% compared with that of the prototype. The proposed method shows potential for analyzing the stress distribution and hemodynamic performance of subregional thickened valves and can further improve the durability of PHVs., (© 2023 John Wiley & Sons Ltd.)

A new general contact model is proposed for preventing inter-leaflet penetration of bio-prosthetic heart valves (BHV) at the end of the systole, which has the advantage of applying kinematic constraints directly and creating smooth free edges. At the end of each time step, the impenetrability constraints and momentum exchange between the impacting bodies are applied separately based on the coefficient of restitution. The contact method is implemented in a rotation-free, large deformation, and thin shell finite-element (FE) framework based on loop's subdivision surfaces. A nonlinear, anisotropic material model for a BHV is employed which uses Fung-elastic constitutive laws for in-plane and bending responses, respectively. The contact model is verified and validated against several benchmark problems. For a BHV-specific validation, the computed strains on different regions of a BHV under constant pressure are compared with experimentally measured data. Finally, dynamic simulations of BHV under physiological pressure waveform are performed for symmetrical and asymmetrical fiber orientations incorporating the new contact model and compared with the penalty contact method. The proposed contact model provides the coaptation area of a functioning BHV during the closing phase for both of the fiber orientations. Our results show that fiber orientation affects the dynamic of leaflets during the opening and closing phases. A swirling motion for the BHV with asymmetrical fiber orientation is observed, similar to experimental data. To include the fluid effects, fluid-structure interaction (FSI) simulation of the BHV is performed and compared to the dynamic results., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

The cerebrovascular blood vessels feed necessary agents such as oxygen, glucose, and so forth. to the brain which maintains the smooth functioning of the human body. However, the blood-brain barrier as a vascular border restricts the entry of drugs that can be necessary for the treatment of neurological disorders. The fluid shear stress in the cerebrovascular blood vessels may regulate the drug delivery in the interface between the cerebrovascular blood vessels and the brain. The intensity of influence by various factors that affects the shear stress in the cerebrovascular blood vessels is scarcely addressed in the present study. A hybrid approach of computational fluid dynamics and Taguchi analysis is proposed to evaluate the influence of various geometrical and operating factors on the shear stress in the microfluidic cerebrovascular channel. Furthermore, the non-Newtonian behavior of blood flow is considered to evaluate the shear stress in the microfluidic cerebrovascular channel. The Newtonian and six non-Newtonian fluids models of Carreau, Carreau-Yasuda, Casson, Cross, Ostwald-de Waele, and Herschel-Bulkley are numerically tested under various conditions of the flow rate, width, and height of the channel to find the viscosity influence on the shear stress. The Taguchi analysis consisting of range and variance analyses is applied to the L 16 orthogonal array to evaluate the effect of various factors on shear stress in terms of influence order, range, F value, and percentage contribution. The parameters for the considered six non-Newtonian fluid models are proposed to accurately map the viscosity behavior with shear strain compared to the actual blood flow behavior. The Newtonian, Carreau, and Carreau-Yasuda non-Newtonian fluid models are found accurately with maximum errors between the experimental and numerical shear stress results as 2.17%, 1.30%, and 1.48%, respectively. The shear stress decreases with an increase in the width and height of the channel and a decrease in the viscosity for all flow rates. The porosity is evaluated as a highly influential factor followed by the flow rate, width, and height of the channel in decreasing order based on their effects on the shear stress. The modified shear stress equation is proposed with an accuracy of 0.96 by integrating the effect of porosity in addition to width, height, flow rate, and viscosity. The in-vitro microfluidic cerebrovascular model could be designed and manufactured based on the proposed results on influence order, F value, and percentage contribution of various factors in direction of achieving the in-vivo level shear stress., (© 2023 John Wiley & Sons Ltd.)