A numerical investigation to evaluate the washout of blood compartments in a total artificial heart.

Total artificial heart (TAH) represents the only valid alternative to heart transplantation, whose number is continuously increasing in recent years. The TAH used in this work, is a biventricular pulsatile, electrically powered, hydraulically actuated flow pump with all components embodied in a single device. One of the major issues for TAHs is the washout capability of the device, strictly correlated with the presence of blood stagnation sites. The aim of this work was to develop a numerical methodology to study the washout coupled with the fluid dynamics evaluation of a total artificial heart under nominal working conditions. The first part of this study focussed on the CT scan analysis of the hybrid membrane kinematics during TAH operation, which was replicated with a fluid-structure interaction simulation in the second part. The difference in percentage between the in vitro and in silico flow rates and stroke volume is 9.7% and 6.3%, respectively. An injection of contrast blood was simulated, and a good washout performance was observed and quantified with the volume fraction of the contrast blood still in the ventricle. The left chamber of the device showed a superior washout performance, with a contrast volume still inside the device after four washout cycles of 6.2%, with the right chamber showing 15%.

Numerical Approach to Study the Behavior of an Artificial Ventricle: Fluid-Structure Interaction Followed By Fluid Dynamics With Moving Boundaries.

Heart failure is a progressive and often fatal pathology among the main causes of death in the world. An implantable total artificial heart (TAH) is an alternative to heart transplantation. Blood damage quantification is imperative to assess the behavior of an artificial ventricle and is strictly related to the hemodynamics, which can be investigated through numerical simulations. The aim of this study is to develop a computational model that can accurately reproduce the hemodynamics inside the left pumping chamber of an existing TAH (Carmat-TAH) together with the displacement of the leaflets of the biological aortic and mitral valves and the displacement of the pericardium-made membrane. The proposed modeling workflow combines fluid-structure interaction (FSI) simulations based on a fixed grid method with computational fluid dynamics (CFD). In particular, the kinematics of the valves is accounted for by means of a dynamic mesh technique in the CFD. The comparison between FSI- and CFD-calculated velocity fields confirmed that the presence of the valves in the CFD model is essential for realistically mimicking blood dynamics, with a percentage difference of 2% during systole phase and 13% during the diastole. The percentage of blood volume in the CFD simulation with a shear stress above the threshold of 50 Pa is less than 0.001%. In conclusion, the application of this workflow to the Carmat-TAH provided consistent results with previous clinical studies demonstrating its utility in calculating local hemodynamic quantities in the presence of complex moving boundaries.

Non-contact tonometry: predicting intraocular pressure using a material-corneal thickness-independent methodology.

Introduction: Glaucoma, a leading cause of blindness worldwide, is primarily caused by elevated intraocular pressure (IOP). Accurate and reliable IOP measurements are the key to diagnose the pathology in time and to provide for effective treatment strategies. The currently available methods for measuring IOP include contact and non contact tonometers (NCT), which estimate IOP based on the corneal deformation caused by an external load, that in the case of NCT is an air pulse. The deformation of the cornea during the tonometry is the result of the coupling between the IOP, the mechanical properties of the corneal tissue, the corneal thickness, and the external force applied. Therefore, there is the need to decouple the four contributions to estimate the IOP more reliably. Methods: This paper aims to propose a new methodology to estimate the IOP based on the analysis of the mechanical work performed by the air jet and by the IOP during the NCT test. A numerical eye model is presented, initially deformed by the action of a falling mass to study the energy balance. Subsequently, Fluid-Structure Interaction (FSI) simulations are conducted to simulate the action of Corvis ST. Results and discussion: The new IOP estimation procedure is proposed based on the results of the simulations. The methodology is centred on the analysis of the time of maximum apex velocity rather than the point of first applanation leading to a new IOP estimation not influenced by the geometrical and mechanical corneal factors.

Improving early detection of keratoconus by Non Contact Tonometry. A computational study and new biomarkers proposal.

Keratoconus is a progressive ocular disorder affecting the corneal tissue, leading to irregular astigmatism and decreased visual acuity. The architectural organization of corneal tissue is altered in keratoconus, however, data from ex vivo testing of biomechanical properties of keratoconic corneas are limited and it is unclear how their results relate to true mechanical properties in vivo. This study explores the mechanical properties of keratoconic corneas through numerical simulations of non-contact tonometry (NCT) reproducing the clinical test of the Corvis ST device. Three sensitivity analyses were conducted to assess the impact of corneal material properties, size, and location of the pathological area on NCT results. Additionally, novel asymmetry-based indices were proposed to better characterize corneal deformations and improve the diagnosis of keratoconus. Our results show that the weakening of corneal material properties leads to increased deformation amplitude and altered biomechanical response. Furthermore, asymmetry indices offer valuable information for locating the pathological tissue. These findings suggest that adjusting the Corvis ST operation, such as a camera rotation, could enhance keratoconus detection and provide insights into the relative position of the affected area. Future research could explore the application of these indices in detecting early-stage keratoconus and assessing the fellow eye's risk for developing the pathology.

On the necessity to include arterial pre-stress in patient-specific simulations of minimally invasive procedures.

Transcatheter aortic valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR) are minimally invasive procedures for treating aortic valves and diseases. Finite element simulations have proven to be valuable tools in predicting device-related complications. In the literature, the inclusion of aortic pre-stress has not been widely investigated. It plays a crucial role in determining the biomechanical response of the vessel and the device-tissue interaction. This study aims at demonstrating how and when to include the aortic pre-stress in patient-specific TAVI and TEVAR simulations. A percutaneous aortic valve and a stent-graft were implanted in aortic models reconstructed from patient-specific CT scans. Two scenarios for each patient were compared, i.e., including and neglecting the wall pre-stress. The neglection of pre-stress underestimates the contact pressure of 48% and 55%, the aorta stresses of 162% and 157%, the aorta strains of 77% and 21% for TAVI and TEVAR models, respectively. The stent stresses are higher than 48% with the pre-stressed aorta in TAVI simulations; while, similar results are obtained in TEVAR cases. The distance between the device and the aorta is similar with and without pre-stress. The inclusion of the aortic wall pre-stress has the capability to give a better representation of the biomechanical behavior of the arterial tissues and the implanted device. It is suggested to include this effect in patient-specific simulations replicating the procedures.

Effect of variability of mechanical properties on the predictive capabilities of vulnerable coronary plaques.

BACKGROUND AND OBJECTIVE: Coronary plaque rupture is a precipitating event responsible for two thirds of myocardial infarctions. Currently, the risk of plaque rupture is computed based on demographic, clinical, and image-based adverse features. However, using these features the absolute event rate per single higher-risk lesion remains low. This work studies the power of a novel framework based on biomechanical markers accounting for material uncertainty to stratify vulnerable and non-vulnerable coronary plaques. METHODS: Virtual histology intravascular ultrasounds from 55 patients, 29 affected by acute coronary syndrome and 26 affected by stable angina pectoris, were included in this study. Two-dimensional vessel cross-sections for finite element modeling (10 sections per plaque) incorporating plaque structure (medial tissue, loose matrix, lipid core and calcification) were reconstructed. A Montecarlo finite element analysis was performed on each section to account for material variability on three biomechanical markers: peak plaque structural stress at diastolic and systolic pressure, and peak plaque stress difference between systolic and diastolic pressures, together with the luminal pressure. Machine learning decision tree classifiers were trained on 75% of the dataset and tested on the remaining 25% with a combination of feature selection techniques. Performance against classification trees based on geometric markers (i.e., luminal, external elastic membrane and plaque areas) was also performed. RESULTS: Our results indicate that the plaque structural stress outperforms the classification capacity of the combined geometric markers only (0.82 vs 0.51 area under curve) when accounting for uncertainty in material parameters. Furthermore, the results suggest that the combination of the peak plaque structural stress at diastolic and systolic pressures with the maximum plaque structural stress difference between systolic and diastolic pressures together with the systolic pressure and the diastolic to systolic pressure gradient is a robust classifier for coronary plaques when the intrinsic variability in material parameters is considered (area under curve equal to [0.91-0.93]). CONCLUSION: In summary, our results emphasize that peak plaque structural stress in combination with the patient's luminal pressure is a potential classifier of plaque vulnerability as it independently considers stress in all directions and incorporates total geometric and compositional features of atherosclerotic plaques.

Validation evidence with experimental and clinical data to establish credibility of TAVI patient-specific simulations.

PURPOSE: The objective of this study is to validate a novel workflow for implementing patient-specific finite element (FE) simulations to virtually replicate the Transcatheter Aortic Valve Implantation (TAVI) procedure. METHODS: Seven patients undergoing TAVI were enrolled. Patient-specific anatomical models were reconstructed from pre-operative computed tomography (CT) scans and subsequentially discretized, considering the native aortic leaflets and calcifications. Moreover, high-fidelity models of CoreValve Evolut R and Acurate Neo2 valves were built. To determine the most suitable material properties for the two stents, an accurate calibration process was undertaken. This involved conducting crimping simulations and fine-tuning Nitinol parameters to fit experimental force-diameter curves. Subsequently, FE simulations of TAVI procedures were conducted. To validate the reliability of the implemented implantation simulations, qualitative and quantitative comparisons with post-operative clinical data, such as angiographies and CT scans, were performed. RESULTS: For both devices, the simulation curves closely matched the experimental data, indicating successful validation of the valves mechanical behaviour. An accurate qualitative superimposition with both angiographies and CTs was evident, proving the reliability of the simulated implantation. Furthermore, a mean percentage difference of 1,79 ± 0,93 % and 3,67 ± 2,73 % between the simulated and segmented final configurations of the stents was calculated in terms of orifice area and eccentricity, respectively. CONCLUSION: This study shows the successful validation of TAVI simulations in patient-specific anatomies, offering a valuable tool to optimize patients care through personalized pre-operative planning. A systematic approach for the validation is presented, laying the groundwork for enhanced predictive modeling in clinical practice.

A finite element model of the embryonic zebrafish heart electrophysiology.

BACKGROUND AND OBJECTIVE: In the last 30 years, a growing interest has involved the study of zebrafish thanks to its physiological characteristics similar to those of humans. The aim of the following work is to create an electrophysiological computational model of the zebrafish heart and lay the foundation for the development of an in-silico model of the zebrafish heart that will allow to study the correlation between pathologies and drug administration with the main electrophysiological parameters as the ECG signal. METHODS: The model considers a whole body and the two chambers of three days post fertilization (3 dpf) zebrafish. A four-variable phenomenological action potential model describes the action potential of different heart regions. Tissue conductivity was calibrated to reproduce the experimentally described activation sequence. RESULTS: The model is able to correctly reproduce the activation sequence and times found in literature, with activation of the atrium and ventricle that correspond to 36 and 59 ms, respectively, and a delay of 14 ms caused by the presence of the atrioventricular band (AV band). Moreover, the obtained in-silico ECG reflects the main characteristics of the zebrafish ECG in good agreement with experimental records, a P-wave with a duration of approximately the total atrial activation, followed by a QRS complex of approximately 109 ms corresponding to ventricle activation. CONCLUSIONS: The model allows the assessment of the main electrophysiological parameters in terms of activation sequence and timing, reproducing monopolar and bipolar ECG signals in line with experimental data. Coupling the proposed model with an electrophysiological detailed action potential model of zebrafish will represent a significant breakthrough toward the development of an in-silico zebrafish heart.

On the need of a scale-dependent material characterization to describe the mechanical behavior of 3D printed Ti6Al4V custom prostheses using finite element models.

Additive manufacturing is widely used in the orthopaedic industry for the high freedom and flexibility in the design and production of personalized custom implants made of Ti6Al4V. Within this context, finite element modeling of 3D printed prostheses is a robust tool both to guide the design phase and to support clinical evaluations, possibly virtually describing the in-vivo behavior of the implant. Given realistic scenarios, a suitable description of the overall implant's mechanical behavior is unavoidable. Considering typical custom prostheses' designs (i.e. acetabular and hemipelvis implants), complex designs involving solid and/or trabeculated parts, and material distribution at different scales hinder a high-fidelity modeling of the prostheses. Moreover, uncertainties in the production and in the material characterization of small parts approaching the accuracy limit of the additive manufacturing technology still exist. While recent works suggest that the mechanical properties of thin 3D-printed parts may be peculiarly affected by specific processing parameters (i.e. powder grain size, printing orientation, samples' thickness) as compared to conventional Ti6Al4V alloy, the current numerical models make gross simplifications in describing the complex material behavior of each part at different scales. The present study focuses on two patient-specific acetabular and hemipelvis prostheses, with the aim of experimentally characterizing and numerically describing the dependency of the mechanical behavior of 3D printed parts on their peculiar scale, therefore, overcoming one major limitation of current numerical models. Coupling experimental activities with finite element analyses, the authors initially characterized 3D printed Ti6Al4V dog-bone samples at different scales, representative of the main material components of the investigated prostheses. Afterwards, the authors implemented the characterized material behaviors into finite element models to compare the implications of adopting scale-dependent vs. conventional scaleindependent approaches in predicting the experimental mechanical behavior of the prostheses in terms of their overall stiffness and the local strain distribution. The material characterization results highlighted the need for a scale-dependent reduction of the elastic modulus for thin samples compared to the conventional Ti6Al4V, which is fundamental to properly describe the overall stiffness and local strain distribution on the prostheses. The presented works demonstrate how an appropriate material characterization and a scale-dependent material description is needed to develop reliable FE models of 3D printed implants characterized by a complex material distribution at different scales.

Applicability assessment for in-silico patient-specific TEVAR procedures.

Thoracic Endovascular Aortic Repair (TEVAR) is a minimally invasive technique to treat thoracic aorta pathologies and consists of placing a self-expandable stent-graft into the pathological region to restore the vessel lumen and recreate a more physiological condition. Exhaustive computational models, namely the finite element analysis, can be implemented to reproduce the clinical procedure. In this context, numerical models, if used for clinical applications, must be reliable and the simulation credibility should be proved to predict clinical procedure outcomes or to build in-silico clinical trials. This work aims first at applying a previously validated TEVAR methodology to a patient-specific case. Then, defining the TEVAR procedure performed on a patient population as the context of use, the overall applicability of the TEVAR modeling is assessed to demonstrate the reliability of the model itself following a step-by-step method based on the ASME V&V40 protocol. Validation evidence sources are identified for the specific context of use and adopted to demonstrate the applicability of the numerical procedure, thereby answering a question of interest that evaluates the deployed stent-graft configuration in the vessel.

Microcatheter tracking in thrombectomy procedures: A finite-element simulation study.

BACKGROUND AND OBJECTIVE: Mechanical thrombectomy is a minimally invasive procedure that aims at removing the occluding thrombus from the vasculature of acute ischemic stroke patients. Thrombectomy success and failure can be studied using in-silico thrombectomy models. Such models require realistic modeling steps to be effective. We here present a new approach to model microcatheter tracking during thrombectomy. METHODS: For 3 patient-specific vessel geometries, we performed finite-element simulations of the microcatheter tracking (1) following the vessel centerline (centerline method) and (2) as a one-step insertion simulation, where the microcatheter tip was advanced along the vessel centerline while its body was free to interact with the vessel wall (tip-dragging method). Qualitative validation of the two tracking methods was performed with the patient's digital subtraction angiography (DSA) images. In addition, we compared simulated thrombectomy outcomes (successful vs unsuccessful thrombus retrieval) and maximum principal stresses on the thrombus between the centerline and tip-dragging method. RESULTS: Qualitative comparison with the DSA images showed that the tip-dragging method more realistically resembles the patient-specific microcatheter-tracking scenario, where the microcatheter approaches the vessel walls. Although the simulated thrombectomy outcomes were similar in terms of thrombus retrieval, the thrombus stress fields (and the associated fragmentation of the thrombus) were strongly different between the two methods, with local differences in the maximum principal stress curves up to 84%. CONCLUSIONS: Microcatheter positioning with respect to the vessel affects the stress fields of the thrombus during retrieval, and therefore, may influence thrombus fragmentation and retrieval in-silico thrombectomy.

Cellular heterogeneity and repolarisation across the atria: an in silico study.

Mechanisms of atrial fibrillation and the susceptibility to reentries can be impacted by the repolarization across the atria. Studies into atrial fibrillation ignore cell-to-cell heterogeneity due to electrotonic coupling. Recent studies show that cellular variability may have a larger impact on electrophysiological behaviour than assumed. This paper aims to determine the impact of cellular heterogeneity on the repolarization phase across the AF remodelled atria. Using a population of models approach, 10 anatomically identical atrial models were created to include cellular heterogeneity. Atrial models were compared with an equivalent homogenous model. Activation, APD90, and repolarization maps were used to compare models. The impact of electrotonic coupling in the tissue was determined through a comparison of RMP, APD20, APD50, APD90, and triangulation between regional atrial tissue and the single cell populations. After calibration, cellular heterogeneity does not impact atrial depolarization. Repolarization patterns were significantly impacted by cellular heterogeneity, with the APD90 across the LA increasing due to heterogeneity and the reverse occurring in the RA. Electrotonic coupling caused a reduction in variability across all biomarkers but did not fully remove variability. Electrotonic coupling resulted in an increase in APD20 and APD50, and reduced triangulation compared to isolated cell populations. Heterogeneity also caused a reduction in triangulation compared with regionally homogeneous atria.

Self-expandable stent for thrombus removal modeling: Solid or beam finite elements?

BACKGROUND: The performance of self-expandable stents is being increasingly studied by means of finite-element analysis. As for peripheral stents, transcatheter valves and stent-grafts, there are numerous computational studies for setting up a proper model, this information is missing for stent-retrievers used in the procedure of thrombus removal in cerebral arteries. It is well known that the selection of the appropriate finite-element dimensions (topology) and formulations (typology) is a fundamental step to set up accurate and reliable computational simulations. In this context, a thorough verification analysis is here proposed, aimed at investigating how the different element typologies and topologies - available to model a stent-retriever - affect simulation results. METHOD: Hexahedral and beam element formulations were analyzed first individually by virtually replicating a crimping test on the device, and then by replicating the thrombectomy procedure aiming at removing a thrombus from a cerebral vessel. In particular, three discretization refinements for each element type and different element formulations including both full and reduced integration were investigated and compared in terms of the resultant radial force of the stent and the stress field generated in the thrombus. RESULTS: The sensitivity analysis on the element formulation performed with the crimping simulations allowed the identification of the optimal setting for each element family. Both setting lead to similar results in terms of stent performance in the virtual thrombectomy and should be used in future studies simulating the mechanical thrombectomy with stent-retrievers. CONCLUSIONS: The carried out virtual thrombectomy procedures confirmed that the beam element formulation results were sufficiently accurate to model the radial force and the performance of the stent-retriever during the procedure. For different self-expandable stents, hexahedral formulation could be essential in stress analysis.

Cardiac cells stimulated with an axial current-like waveform reproduce electrophysiological properties of tissue fibers.

BACKGROUND AND OBJECTIVE: In silico electrophysiological models are generally validated by comparing simulated results with experimental data. When dealing with single-cell and tissue scales simultaneously, as occurs frequently during model development and calibration, the effects of inter-cellular coupling should be considered to ensure the trustworthiness of model predictions. The hypothesis of this paper is that the cell-tissue mismatch can be reduced by incorporating the effects of conduction into the single-cell stimulation current. METHODS: Five different stimulation waveforms were applied to the human ventricular O'Hara-Rudy cell model. The waveforms included the commonly used monophasic and biphasic (symmetric and asymmetric) pulses, a triangular waveform and a newly proposed asymmetric waveform (stimulation A) that resembles the transmembrane current associated with AP conduction in tissue. A comparison between single-cell and fiber simulated results was established by computing the relative difference between the values of AP-derived properties at different scales, and by evaluating the differences in the contributions of ionic conductances to each evaluated property. As a proof of the benefit, we investigated multi-scale differences in the simulation of the effects induced by dofetilide, a selective IKr blocker with high torsadogenic risk, on ventricular repolarization at different pacing rates. RESULTS: Out of the five tested stimulation waveforms, stimulation A produced the closest correspondence between cell and tissue simulations in terms of AP properties at steady-state and under dynamic pacing and of ionic contributors to those AP properties. Also, stimulation A reproduced the effects of dofetilide better than the other alternative waveforms, mirroring the 'beat-skipping' behavior observed at fast pacing rates in experiments with human tissue. CONCLUSIONS: The proposed stimulation current waveform accounts for inter-cellular coupling effects by mimicking cell excitation during AP conduction. The proposed waveform improves the correspondence between simulation scales, which could improve the trustworthiness of single-cell simulations without adding computational cost.

A detailed methodology to model the Non Contact Tonometry: a Fluid Structure Interaction study.

Understanding the corneal mechanical properties has great importance in the study of corneal pathologies and the prediction of refractive surgery outcomes. Non-Contact Tonometry (NCT) is a non-invasive diagnostic tool intended to characterize the corneal tissue response in vivo by applying a defined air-pulse. The biomarkers inferred from this test can only be considered as indicators of the global biomechanical behaviour rather than the intrinsic biomechanical properties of the corneal tissue. A possibility to isolate the mechanical response of the corneal tissue is the use of an inverse finite element method, which is based on accurate and reliable modelling. Since a detailed methodology is still missing in the literature, this paper aims to construct a high-fidelity finite-element model of an idealized 3D eye for in silico NCT. A fluid-structure interaction (FSI) simulation is developed to virtually apply a defined air-pulse to a 3D idealized eye model comprising cornea, limbus, sclera, lens and humors. Then, a sensitivity analysis is performed to examine the influence of the intraocular pressure (IOP) and the structural material parameters on three biomarkers associated with corneal deformation. The analysis reveals the requirements for the in silico study linked to the correct reproduction of three main aspects: the air pressure over the cornea, the biomechanical properties of the tissues, and the IOP. The adoption of an FSI simulation is crucial to capture the correct air pressure profile over the cornea as a consequence of the air-jet. Regarding the parts of the eye, an anisotropic material should be used for the cornea. An important component is the sclera: the stiffer the sclera, the lower the corneal deformation due to the air-puff. Finally, the fluid-like behavior of the humors should be considered in order to account for the correct variation of the IOP during the test which will, otherwise, remain constant. The development of a strong FSI tool amenable to model coupled structures and fluids provides the basis to find the biomechanical properties of the corneal tissue in vivo.

Combined stent-retriever and aspiration intra-arterial thrombectomy performance for fragmentable blood clots: A proof-of-concept computational study.

Mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) patients typically involves use of stent retrievers or aspiration catheters alone or in combination. For in silico trials of AIS patients, it is crucial to incorporate the possibility of thrombus fragmentation during the intervention. This study focuses on two aspects of the thrombectomy simulation: i) Thrombus fragmentation on the basis of a failure model calibrated with experimental tests on clot analogs; ii) the combined stent-retriever and aspiration catheter MT procedure is modeled by adding both the proximal balloon guide catheter and the distal access catheter. The adopted failure criterion is based on maximum principal stress threshold value. If elements of the thrombus exceed this criterion during the retrieval simulation, then they are deleted from the calculation. Comparison with in-vitro tests indicates that the simulation correctly reproduces the procedures predicting thrombus fragmentation in the case of red blood cells rich thrombi, whereas non-fragmentation is predicted for fibrin-rich thrombi. Modeling of balloon guide catheter prevents clot fragments' embolization to further distal territories during MT procedure.

Validation and Verification of High-Fidelity Simulations of Thoracic Stent-Graft Implantation.

Thoracic Endovascular Aortic Repair (TEVAR) is the preferred treatment option for thoracic aortic pathologies and consists of inserting a self-expandable stent-graft into the pathological region to restore the lumen. Computational models play a significant role in procedural planning and must be reliable. For this reason, in this work, high-fidelity Finite Element (FE) simulations are developed to model thoracic stent-grafts. Experimental crimp/release tests are performed to calibrate stent-grafts material parameters. Stent pre-stress is included in the stent-graft model. A new methodology for replicating device insertion and deployment with explicit FE simulations is proposed. To validate this simulation, the stent-graft is experimentally released into a 3D rigid aortic phantom with physiological anatomy and inspected in a computed tomography (CT) scan at different time points during deployment with an ad-hoc set-up. A verification analysis of the adopted modeling features compared to the literature is performed. With the proposed methodology the error with respect to the CT is on average 0.92 ± 0.64%, while it is higher when literature models are adopted (on average 4.77 ± 1.83%). The presented FE tool is versatile and customizable for different commercial devices and applicable to patient-specific analyses.

In silico approaches for transcatheter aortic valve replacement inspection.

Introduction: Increasing applications of transcatheter aortic valve replacement (TAVR) to treat high- or medium-risk patients with aortic diseases have been proposed in recent years. Despite its increasing use, many influential factors are still to be understood. Furthermore, innovative applications of TAVR such as in bicuspid aortic valves or in low-risk patients are emerging in clinical use. Numerical analyses are increasingly used to reproduce clinical treatments. The future trends in this area are foreseen for in silico trials and personalized medicine. Areas covered: This review paper analyzes the recent years (Jan 2018 - Aug 2020) of in silico studies simulating the behavior of transcatheter aortic valves with emphasis on the addressed clinical question and the used modeling strategies. The manuscripts are firstly classified based on their clinical hypothesis. A second classification is based on the adopted modeling approach in terms of patient domain, device modeling, and inclusion or exclusion of the fluid domain. Expert opinion: The TAVR can be virtually performed in numerous vessel geometries and with different devices. This versatility allows a rapid evaluation of the feasibility of different implantation approaches for specific patients, and patient populations, resulting in faster and safer introduction or optimization of new treatments or devices.

Effect of myofibril architecture on the active contraction of dystrophic muscle. A mathematical model.

Duchenne muscular dystrophy (DMD) is a muscle degenerative disease caused by a mutation in the dystrophin gene. The lack of dystrophin leads to persistent inflammation, degeneration/regeneration cycles of muscle fibers, Ca2＋ dysregulation, incompletely regenerated fibers, necrosis, fibrotic tissue replacement, and alterations in the fiber ultrastructure i.e., myofibril misalignment and branched fibers. This work aims to develop a comprehensive chemo-mechanical model of muscle-skeletal tissue accounting for dispersion in myofibrillar orientations, in addition to the disorders in sarcomere pattern and the fiber branching. The model results confirm a significant correlation between the myofibrillar dispersion and the reduction of isometric force in the dystrophic muscle and indicate that the reduction of contraction velocity in the dystrophic muscle seems to be associated with the local disorders in the sarcomere patterns of the myofibrils. Also, the implemented model can predict the force-velocity response to both concentric and eccentric loading. The resulting model represents an original approach to account for defects in the muscle ultrastructure caused by pathologies as DMD.

Applicability analysis to evaluate credibility of an in silico thrombectomy procedure.

Intra-arterial thrombectomy is a minimally invasive procedure in which an obstructing thrombus (clot) is removed using a minimally-invasive device: a stent-retriever. The stent-retriever is first deployed, and then the thrombus is removed during stent-retriever retraction. This procedure can be simulated using a detailed computational model. However, to be useful for an in silico trial in a clinical setting, model credibility should be demonstrated. The aim of this work is to apply a credibility process for the validation phases to the thrombectomy procedure in order to deem it credible for use in an in silico trial. Validation evidence is proposed for the identified context of use and then used to build credibility to the numerical model. Applicability of the proposed model is justified and assessed using a rigorous step-by-step method based on the ASME V&V40 protocol.