High-Frequency Fluctuations in Post-stenotic Patient Specific Carotid Stenosis Fluid Dynamics: A Computational Fluid Dynamics Strategy Study.

PURPOSE: Screening of asymptomatic carotid stenoses is performed by auscultation of the carotid bruit, but the sensitivity is poor. Instead, it has been suggested to detect carotid bruit as neck's skin vibrations. We here take a first step towards a computational fluid dynamics proof-of-concept study, and investigate the robustness of our numerical approach for capturing high-frequent fluctuations in the post-stenotic flow. The aim was to find an ideal solution strategy from a pragmatic point of view, balancing accuracy with computational cost comparing an under-resolved direct numerical simulation (DNS) approach vs. three common large eddy simulation (LES) models (static/dynamic Smagorinsky and Sigma). METHOD: We found a reference solution by performing a spatial and temporal refinement study of a stenosed carotid bifurcation with constant flow rate. The reference solution [Formula: see text] was compared against LES for both a constant and pulsatile flow. RESULTS: Only the Sigma and Dynamic Smagorinsky models were able to replicate the flow field of the reference solution for a pulsatile simulation, however the computational cost of the Sigma model was lower. However, none of the sub-grid scale models were able to replicate the high-frequent flow in the peak-systolic constant flow rate simulations, which had a higher mean Reynolds number. CONCLUSIONS: The Sigma model was the best combination between accuracy and cost for simulating the pulsatile post-stenotic flow field, whereas for the constant flow rate, the under-resolved DNS approach was better. These results can be used as a reference for future studies investigating high-frequent flow features.

Assessing the Performance of Ultrafast Vector Flow Imaging in the Neonatal Heart via Multiphysics Modeling and In Vitro Experiments.

Ultrafast vector flow imaging would benefit newborn patients with congenital heart disorders, but still requires thorough validation before translation to clinical practice. This paper investigates 2-D speckle tracking (ST) of intraventricular blood flow in neonates when transmitting diverging waves at ultrafast frame rate. Computational and in vitro studies enabled us to quantify the performance and identify artifacts related to the flow and the imaging sequence. First, synthetic ultrasound images of a neonate's left ventricular flow pattern were obtained with the ultrasound simulator Field II by propagating point scatterers according to 3-D intraventricular flow fields obtained with computational fluid dynamics (CFD). Noncompounded diverging waves (opening angle of 60°) were transmitted at a pulse repetition frequency of 9 kHz. ST of the B-mode data provided 2-D flow estimates at 180 Hz, which were compared with the CFD flow field. We demonstrated that the diastolic inflow jet showed a strong bias in the lateral velocity estimates at the edges of the jet, as confirmed by additional in vitro tests on a jet flow phantom. Furthermore, ST performance was highly dependent on the cardiac phase with low flows (<5 cm/s), high spatial flow gradients, and out-of-plane flow as deteriorating factors. Despite the observed artifacts, a good overall performance of 2-D ST was obtained with a median magnitude underestimation and angular deviation of, respectively, 28% and 13.5° during systole and 16% and 10.5° during diastole.

Fluid-Structure Interaction Simulation of Prosthetic Aortic Valves: Comparison between Immersed Boundary and Arbitrary Lagrangian-Eulerian Techniques for the Mesh Representation.

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results.

Assessment of shear stress related parameters in the carotid bifurcation using mouse-specific FSI simulations.

The ApoE(-)(/)(-) mouse is a common small animal model to study atherosclerosis, an inflammatory disease of the large and medium sized arteries such as the carotid artery. It is generally accepted that the wall shear stress, induced by the blood flow, plays a key role in the onset of this disease. Wall shear stress, however, is difficult to derive from direct in vivo measurements, particularly in mice. In this study, we integrated in vivo imaging (micro-Computed Tomography-µCT and ultrasound) and fluid-structure interaction (FSI) modeling for the mouse-specific assessment of carotid hemodynamics and wall shear stress. Results were provided for 8 carotid bifurcations of 4 ApoE(-)(/)(-) mice. We demonstrated that accounting for the carotid elasticity leads to more realistic flow waveforms over the complete domain of the model due to volume buffering capacity in systole. The 8 simulated cases showed fairly consistent spatial distribution maps of time-averaged wall shear stress (TAWSS) and relative residence time (RRT). Zones with reduced TAWSS and elevated RRT, potential indicators of atherosclerosis-prone regions, were located mainly at the outer sinus of the external carotid artery. In contrast to human carotid hemodynamics, no flow recirculation could be observed in the carotid bifurcation region.

Differential impact of local stiffening and narrowing on hemodynamics in repaired aortic coarctation: an FSI study.

Even after successful treatment of aortic coarctation, a high risk of cardiovascular morbidity and mortality remains. Uncertainty exists on the factors contributing to this increased risk among which are the presence of (1) a residual narrowing leading to an additional resistance and (2) a less distensible zone disturbing the buffer function of the aorta. As the many interfering factors and adaptive physiological mechanisms present in vivo prohibit the study of the isolated impact of these individual factors, a numerical fluid-structure interaction model is developed to predict central hemodynamics in coarctation treatment. The overall impact of a stiffening on the hemodynamics is limited, with a small increase in systolic pressure (up to 8 mmHg) proximal to the stiffening which is amplified with increasing stiffening and length. A residual narrowing, on the other hand, affects the hemodynamics significantly. For a short segment (10 mm), the combination of a stiffening and narrowing (coarctation index 0.5) causes an increase in systolic pressure of 58 mmHg, with 31 mmHg due to narrowing and an additional 27 mmHg due to stiffening. For a longer segment (25 mm), an increase in systolic pressure of 50 mmHg is found, of which only 9 mmHg is due to stiffening.

An animal-specific FSI model of the abdominal aorta in anesthetized mice.

Recent research has revealed that angiotensin II-induced abdominal aortic aneurysm in mice can be related to medial ruptures occurring in the vicinity of abdominal side branches. Nevertheless a thorough understanding of the biomechanics near abdominal side branches in mice is lacking. In the current work we present a mouse-specific fluid-structure interaction (FSI) model of the abdominal aorta in ApoE(-/-) mice that incorporates in vivo stresses. The aortic geometry was based on contrast-enhanced in vivo micro-CT images, while aortic flow boundary conditions and material model parameters were based on in vivo high-frequency ultrasound. Flow waveforms predicted by FSI simulations corresponded better to in vivo measurements than those from CFD simulations. Peak-systolic principal stresses at the inner and outer aortic wall were locally increased caudal to the celiac and left lateral to the celiac and mesenteric arteries. Interestingly, these were also the locations at which a tear in the tunica media had been observed in previous work on angiotensin II-infused mice. Our preliminary results therefore suggest that local biomechanics play an important role in the pathophysiology of branch-related ruptures in angiotensin-II infused mice. More elaborate follow-up research is needed to demonstrate the role of biomechanics and mechanobiology in a longitudinal setting.

The aortic reservoir-wave as a paradigm for arterial haemodynamics: insights from three-dimensional fluid-structure interaction simulations in a model of aortic coarctation.

BACKGROUND: The reservoir-wave paradigm considers aortic pressure as the superposition of a 'reservoir pressure', directly related to changes in reservoir volume, and an 'excess' component ascribed to wave dynamics. The change in reservoir pressure is assumed to be proportional to the difference between aortic inflow and outflow (i.e. aortic volume changes), an assumption that is virtually impossible to validate in vivo. The aim of this study is therefore to apply the reservoir-wave paradigm to aortic pressure and flow waves obtained from three-dimensional fluid-structure interaction simulations in a model of a normal aorta, aortic coarctation (narrowed descending aorta) and stented coarctation (stiff segment in descending aorta). METHOD AND RESULTS: We found no unequivocal relation between the intraaortic volume and the reservoir pressure for any of the simulated cases. When plotted in a pressure-volume diagram, hysteresis loops are found that are looped in a clockwise way indicating that the reservoir pressure is lower than the pressure associated with the change in volume. The reservoir-wave analysis leads to very high excess pressures, especially for the coarctation models, but to surprisingly little changes of the reservoir component despite the impediment of the buffer capacity of the aorta. CONCLUSION: With the observation that reservoir pressure is not related to the volume in the aortic reservoir in systole, an intrinsic assumption in the wave-reservoir concept is invalidated and, consequently, also the assumption that the excess pressure is the component of pressure that can be attributed to wave travel and reflection.

Wave reflection leads to over- and underestimation of local wave speed by the PU- and QA-loop methods: theoretical basis and solution to the problem.

Single-point methods such as the PU- and QA-loop methods are used to estimate local pulse wave velocity (PWVPU and PWVQA) in arteries from a combination of pressure (P), flow (Q), velocity (U) or cross-sectional area (A) waveforms. Available data indicate that the PU-loop method tends to overestimate PWV, while the QA-loop method tends to underestimate. Wave reflection has been suggested as a factor playing a role in the agreement between different methods. In this work, we first provide a theoretical basis to (i) demonstrate the interference of wave reflection with the PU-loop method for both solitary sinusoidal waves as well as physiological waveforms; (ii) develop an operator-independent method to correct for the presence of reflections. Fluid-structure interaction simulations in a tube and carotid artery model with known mechanical properties confirm the theory. For the carotid artery model, PWVPU severely overestimates PWV, while PWVQA underestimates PWV. Correction (leading to an estimate termed PWV1-5) seems to eliminate the impact of reflections. Finally, methods are applied in vivo. Compared to PWVPU and PWVQA, PWV1-5 leads to significantly better correlations of carotid PWV with PWV derived from carotid distensibility based on the Bramwell-Hill equation (with r(2) improving from about 0.25 to 0.91). We conclude that neither the PU-loop nor the QA-loop method provides reliable estimates of local PWV in settings where wave reflections are present-even when the PU- or QA-loops show a linear segment. They offer no alternative for the Bramwell-Hill based approach and their application should therefore be discouraged, especially for the carotid artery, although caution is probably warranted in general.

A 3D porous media liver lobule model: the importance of vascular septa and anisotropic permeability for homogeneous perfusion.

The hepatic blood circulation is complex, particularly at the microcirculatory level. Previously, 2D liver lobule models using porous media and a 3D model using real sinusoidal geometries have been developed. We extended these models to investigate the role of vascular septa (VS) and anisotropic permeability. The lobule was modelled as a hexagonal prism (with or without VS) and the tissue was treated as a porous medium (isotropic or anisotropic permeability). Models were solved using computational fluid dynamics. VS inclusion resulted in more spatially homogeneous perfusion. Anisotropic permeability resulted in a larger axial velocity component than isotropic permeability. A parameter study revealed that results are most sensitive to the lobule size and radial pressure drop. Our model provides insight into hepatic microhaemodynamics, and suggests that inclusion of VS in the model leads to perfusion patterns that are likely to reflect physiological reality. The model has potential for applications to unphysiological and pathological conditions.

Measurement of small molecule diffusion with an optofluidic silicon chip.

In this work we explore the micro-ring resonator platform to study the diffusion-driven mass transport of small molecules within microfluidic channels. The micro-ring resonators are integrated on a silicon-on-insulator photonic chip and combined with microfluidics in poly(dimethylsiloxane) (PDMS). We apply a strong initial gradient in the solute concentration and use the micro-ring resonators to observe how this concentration evolves over time and space. This can be achieved by tracking the optical resonances of multiple micro-rings as they shift with changing solute concentration. Experiments are performed for both glucose and NaCl and at different temperatures. The measured concentration profiles are used to calculate the diffusion coefficient of both glucose and NaCl in water. The good agreement between measurement and theoretical prediction demonstrates the relevance of this method.

Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge.

Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

Velocity profiles in the human ductus venosus: a numerical fluid structure interaction study.

The veins distributing oxygenated blood from the placenta to the fetal body have been given much attention in clinical Doppler velocimetry studies, in particular the ductus venosus. The ductus venosus is embedded in the left liver lobe and connects the intra-abdominal portion of the umbilical vein (IUV) directly to the inferior vena cava, such that oxygenated blood can bypass the liver and flow directly to the fetal heart. In the current work, we have developed a mathematical model to assist the clinical assessment of volumetric flow rate at the inlet of the ductus venosus. With a robust estimate of the velocity profile shape coefficient (VC), the volumetric flow rate may be estimated as the product of the time-averaged cross-sectional area, the time-averaged cross-sectional maximum velocity and the VC. The time average quantities may be obtained from Doppler ultrasound measurements, whereas the VC may be estimated from numerical simulations. The mathematical model employs a 3D fluid structure interaction model of the bifurcation formed by the IUV, the ductus venosus and the left portal vein. Furthermore, the amniotic portion of the umbilical vein, the right liver lobe and the inferior vena cava were incorporated as lumped model boundary conditions for the fluid structure interaction model. A hyperelastic material is used to model the structural response of the vessel walls, based on recently available experimental data for the human IUV and ductus venous. A parametric study was constructed to investigate the VC at the ductus venosus inlet, based on a reference case for a human fetus at 36 weeks of gestation. The VC was found to be [Formula: see text] (Mean [Formula: see text] SD of parametric case study), which confirms previous studies in the literature on the VC at the ductus venosus inlet. Additionally, CFD simulations with rigid walls were performed on a subsection of the parametric case study, and only minor changes in the predicted VCs were observed compared to the FSI cases. In conclusion, the presented mathematical model is a promising tool for the assessment of ductus venosus Doppler velocimetry.

Modeling hemodynamics in vascular networks using a geometrical multiscale approach: numerical aspects.

On the one hand the heterogeneity of the circulatory system requires the use of different models in its different compartments, featuring different assumptions on the spatial degrees of freedom. On the other hand, the mutual interactions between its compartments imply that these models should preferably not be considered separately. These requirements have led to the concept of geometrical multiscale modeling, where the main idea is to couple 3D models with reduced 1D and/or 0D models. As such detailed information on the flow field in a specific region of interest can be obtained while accounting for the global circulation. However, the combination of models with different mathematical features gives rise to many difficulties such as the assignment of boundary conditions at the interface between two models and the development of robust coupling algorithms, as the subproblems are usually solved in a partitioned way. This review aims to give an overview of the most important aspects concerning 3D-1D-0D coupled models. In addition, some applications are presented in order to illustrate the potentialities of these coupled models.

Comparison of non-invasive methods for measurement of local pulse wave velocity using FSI-simulations and in vivo data.

In the search for better predictors of cardiovascular events, pulse wave velocity (PWV) has gained considerable interest. We compared three single-location methods to locally estimate PWV based on simultaneous measurements of pressure (P), velocity (U) or arterial diameter (D): the PU, ln(D)U and QA-method. First, the performance of these methods was analyzed using 3D fluid-structure interaction simulations (FSI) in a tube and patient-specific carotid artery. We demonstrated that the outcome was dependent on whether the methods were tested in the ideal conditions of a 3D axisymmetrical and reflection-free tube or in the more realistic setup of a carotid artery. The three single-location PWV methods performed similarly in the tube (4.29 m/s for PU, 4.44 m/s for ln(D)U and 4.38 m/s for QA) while the carotid data showed that the PU-method dramatically overestimates PWV (9.16 m/s), and the ln(D)U and QA-method underestimate (3.86 and 3.84 m/s, respectively). The erroneously high wavespeeds from the PU-method were attributed to wave reflections, which was confirmed by measurements in 37 healthy adults. This in vivo study showed similar discrepancies between the 3 single-location techniques as present in the carotid simulations, with the difference between the PU- and ln(D)U-method related to the magnitude of wave reflection.

Effect of the degree of LAD stenosis on "competitive flow" and flow field characteristics in LIMA-to-LAD bypass surgery.

The long-term patency of the left internal mammary artery (LIMA) in left anterior descending (LAD) coronary stenosis bypass surgery is believed to be related to the degree of competitive flow between the LAD and LIMA. To investigate the effect of the LAD stenosis severity on this phenomenon and on haemodynamics in the LIMA and anastomosis region, a numerical LIMA-LAD model was developed based on 3D geometric (obtained from a cast) and hemodynamic data from an experimental pig study. Proximal LAD pressure was used as upstream boundary condition. The model counted 13 outlets (12 septal arteries and the distal LAD) where flow velocities were imposed in systole, while myocardial conductance was imposed in diastole via an implicit scheme. LAD stenoses of 100 (total occlusion), 90, 75 and 0 % area reduction were constructed. Low degree of LAD stenosis was associated with highly competitive flow and low wall shear stress (WSS) in the LIMA, an unfavourable hemodynamic regime which might contribute to WSS-related remodelling of the LIMA and suboptimal long-term LIMA bypass performance.

Perfusion characteristics of the human hepatic microcirculation based on three-dimensional reconstructions and computational fluid dynamic analysis.

The perfusion of the liver microcirculation is often analyzed in terms of idealized functional units (hexagonal liver lobules) based on a porous medium approach. More elaborate research is essential to assess the validity of this approach and to provide a more adequate and quantitative characterization of the liver microcirculation. To this end, we modeled the perfusion of the liver microcirculation using an image-based three-dimensional (3D) reconstruction of human liver sinusoids and computational fluid dynamics techniques. After vascular corrosion casting, a microvascular sample (±0.134 mm(3)) representing three liver lobules, was dissected from a human liver vascular replica and scanned using a high resolution (2.6 µm) micro-CT scanner. Following image processing, a cube (0.15 × 0.15 × 0.15 mm(3)) representing a sample of intertwined and interconnected sinusoids, was isolated from the 3D reconstructed dataset to define the fluid domain. Three models were studied to simulate flow along three orthogonal directions (i.e., parallel to the central vein and in the radial and circumferential directions of the lobule). Inflow and outflow guidances were added to facilitate solution convergence, and good quality volume meshes were obtained using approximately 9 × 10(6) tetrahedral cells. Subsequently, three computational fluid dynamics models were generated and solved assuming Newtonian liquid properties (viscosity 3.5 mPa s). Post-processing allowed to visualize and quantify the microvascular flow characteristics, to calculate the permeability tensor and corresponding principal permeability axes, as well as the 3D porosity. The computational fluid dynamics simulations provided data on pressure differences, preferential flow pathways and wall shear stresses. Notably, the pressure difference resulting from the flow simulation parallel to the central vein (0-100 Pa) was clearly smaller than the difference from the radial (0-170 Pa) and circumferential (0-180 Pa) flow directions. This resulted in a higher permeability along the central vein direction (k(d,33) = 3.64 × 10(-14) m(2)) in comparison with the radial (k(d,11) = 1.56 × 10(-14) m(2)) and circumferential (k(d,22) = 1.75 × 10(-14) m(2)) permeabilities which were approximately equal. The mean 3D porosity was 14.3. Our data indicate that the human hepatic microcirculation is characterized by a higher permeability along the central vein direction, and an about two times lower permeability along the radial and circumferential directions of a lobule. Since the permeability coefficients depend on the flow direction, (porous medium) liver microcirculation models should take into account sinusoidal anisotropy.

A fast strong coupling algorithm for the partitioned fluid-structure interaction simulation of BMHVs.

The numerical simulation of Bileaflet Mechanical Heart Valves (BMHVs) has gained strong interest in the last years, as a design and optimisation tool. In this paper, a strong coupling algorithm for the partitioned fluid-structure interaction simulation of a BMHV is presented. The convergence of the coupling iterations between the flow solver and the leaflet motion solver is accelerated by using the Jacobian with the derivatives of the pressure and viscous moments acting on the leaflets with respect to the leaflet accelerations. This Jacobian is numerically calculated from the coupling iterations. An error analysis is done to derive a criterion for the selection of useable coupling iterations. The algorithm is successfully tested for two 3D cases of a BMHV and a comparison is made with existing coupling schemes. It is observed that the developed coupling scheme outperforms these existing schemes in needed coupling iterations per time step and CPU time.

Accuracy of carotid strain estimates from ultrasonic wall tracking: a study based on multiphysics simulations and in vivo data.

We used a multiphysics model to assess the accuracy of carotid strain estimates derived from a 1-D ultrasonic wall tracking algorithm. The presented tool integrates fluid-structure interaction (FSI) simulations with an ultrasound simulator (Field II), which allows comparison of the ultrasound (US) images with a ground truth. Field II represents tissue as random points on which US waves reflect and whose position can be updated based on the flow field and vessel wall deformation from FSI. We simulated the RF-signal of a patient-specific carotid bifurcation, including the blood pool as well as the vessel wall and surrounding tissue. Distension estimates were obtained from a wall tracking algorithm using tracking points at various depths within the wall, and further processed to assess radial and circumferential strain. The simulated data demonstrated that circumferential strain can be estimated with reasonable accuracy (especially for the common carotid artery and at the lumen-intima and media-adventitia interface), but the technique does not allow to reliably assess intra-arterial radial strain. These findings were supported by in vivo data of 10 healthy adults, showing similar circumferential and radial strain profiles throughout the arterial wall. We concluded that these deviations are present due to the complex 3-D vessel wall deformation, the presence of specular reflections and, to a lesser extent, the spatially varying beam profile, with the error depending on the phase in the cardiac cycle and the scanning location.

The upstream boundary condition influences the leaflet opening dynamics in the numerical FSI simulation of an aortic BMHV.

In this paper, the influence of the upstream boundary condition in the numerical simulation of an aortic bileaflet mechanical heart valve (BMHV) is studied. Three three-dimensional cases with different upstream boundary conditions are compared. The first case consists of a rigid straight tube with a velocity profile at its inlet. In the second case, the upstream geometry is a contracting left ventricle (LV), positioned symmetrically with respect to the valve. In the last case, the LV is positioned asymmetrical with respect to the valve. The cases are used to simulate the same three-dimensional BMHV. The change in time of the LV volume is calculated such that the flow rate through the valve is identical in each case. The opening dynamics of the BMHV are modelled using fluid-structure interaction. The simulations show that differences occur in the leaflet movement of the three cases. In particular, with the asymmetric LV, one of the leaflets impacts the blocking mechanism at its open position with a 34% higher velocity than when using the velocity profile, and with an 88% higher velocity than in the symmetric LV case. Therefore, when simulating such an impact, the upstream boundary condition needs to be chosen carefully.