Project description:To relate the subcellular molecular events to organ level physiology in heart, we have developed a three-dimensional finite-element-based simulation program incorporating the cellular mechanisms of excitation-contraction coupling and its propagation, and simulated the fluid-structure interaction involved in the contraction and relaxation of the human left ventricle. The FitzHugh-Nagumo model and four-state model representing the cross-bridge kinetics were adopted for cellular model. Both ventricular wall and blood in the cavity were modeled by finite element mesh. An arbitrary Lagrangian Eulerian finite element method with automatic mesh updating has been formulated for large domain changes, and a strong coupling strategy has been taken. Using electrical analog of pulmonary circulation and left atrium as a preload and the windkessel model as an afterload, dynamics of ventricular filling as well as ejection was simulated. We successfully reproduced the biphasic filling flow consisting of early rapid filling and atrial contraction similar to that reported in clinical observation. Furthermore, fluid-structure analysis enabled us to analyze the wave propagation velocity of filling flow. This simulator can be a powerful tool for establishing a link between molecular abnormality and the clinical disorder at the macroscopic level.
Project description:Total cavopulmonary connection (TCPC) hemodynamics has been hypothesized to be associated with long-term complications in single ventricle heart defect patients. Rigid wall assumption has been commonly used when evaluating TCPC hemodynamics using computational fluid dynamics (CFD) simulation. Previous study has evaluated impact of wall compliance on extra-cardiac TCPC hemodynamics using fluid-structure interaction (FSI) simulation. However, the impact of ignoring wall compliance on the presumably more compliant intra-atrial TCPC hemodynamics is not fully understood. To narrow this knowledge gap, this study aims to investigate impact of wall compliance on an intra-atrial TCPC hemodynamics. A patient-specific model of an intra-atrial TCPC is simulated with an FSI model. Patient-specific 3D TCPC anatomies were reconstructed from transverse cardiovascular magnetic resonance images. Patient-specific vessel flow rate from phase-contrast magnetic resonance imaging (MRI) at the Fontan pathway and the superior vena cava under resting condition were prescribed at the inlets. From the FSI simulation, the degree of wall deformation was compared with in vivo wall deformation from phase-contrast MRI data as validation of the FSI model. Then, TCPC flow structure, power loss and hepatic flow distribution (HFD) were compared between rigid wall and FSI simulation. There were differences in instantaneous pressure drop, power loss and HFD between rigid wall and FSI simulations, but no difference in the time-averaged quantities. The findings of this study support the use of a rigid wall assumption on evaluation of time-averaged intra-atrial TCPC hemodynamic metric under resting breath-held condition.
Project description:Electrochemical (EC) carbon dioxide (CO2) reduction, where CO2 is converted to value-added products such as fuel precursors, plays a key role in helping the world's energy system reach net-zero carbon emissions. Simulations of EC cells provide valuable insight into their operation since detailed experimental results on short length and time scales are difficult to obtain. In this work, we construct a 1D simulation of a membrane-electrode-assembly EC cell for CO2 reduction, using a porous silver gas diffusion cathode. We run the simulation under different electrolyte conditions, showing how the cell performance is affected. We then perform a sensitivity analysis of all input parameters to the simulation, which has not been presented before in the literature. We show that the CO partial current density (i CO) is significantly affected by each input parameter of the simulation. i CO is most sensitive to EC kinetic parameters (i 0/α) of all EC reactions, with a 1% change in α resulting in up to 6% change in i CO. Since there is uncertainty associated with the value of each input parameter, this indicates that infidelity between experiment and simulation is likely, and thus, caution should be practiced when comparing experimental results to simulation results. Further, we show that the large range of conditions simulated in literature helps to explain the large variance in reported values of i 0 and α. The results of this paper demonstrate the potential of sensitivity analysis methods to quickly optimize aspects of cell performance (CO2 utilization, Faradaic efficiency, etc.).
Project description:Untreated tricuspid valve regurgitation (TR) is associated with increased rates of mortality, morbidity, and hospitalization. Current pharmacological and surgical treatment options for TR are limited. MitraClip (MC), an edge-to-edge percutaneous intervention, has been reported to be effective for treatment of TR. The goal of this study was to examine the effects of MC position on TR, using a multiphysics fluid-structure-interaction (FSI) analysis. The computational set up included the tricuspid valve (TV), the chordae tendineae, the blood particles, and a tube that surrounded the leaflets and blood particles. The leaflets and chordae were modeled as hyperelastic materials, and blood was modeled using smoothed particle hydrodynamics. FSI analysis was conducted for blood flow through the closed valve for multiple simulations that account for normal, diseased, and treated conditions of the TV. To simulate the diseased TV, a group of chordae between septal and pulmonary leaflets were removed from the normal TV, which produced increased regurgitation. Four MC treated scenarios were considered: i) one MC near the annulus, ii) one MC approximately midway between the annulus and leaflet tip, iii) one MC near the leaflet tip, iv) two MCs: one approximately midway between the annulus and leaflet tip, and one close to the leaflet tip. The TR increased in diseased TV (7.5%) compared to normal TV (2.5%). All MC treated scenarios decreased TR. The MC located near the midway point between the annulus and leaflet tip led to largest decrease in TR (75.2% compared to the untreated condition). The MC located near the leaflet tip was associated with lowest reduction in TR (2.2% compared to the untreated condition). When two MCs were used, reduction in TR was relatively high (68.7%), but TR was not improved compared to the optimal single MC. MC caused high stresses in the vicinity of the clipping area in all conditions; the highest occurred when the MC was near the leaflet tips. Using a quantitative computational approach, we confirm previous clinical reports on the efficacy of MC for treatment of TR. The results of this study could lead to the design of more efficient MC interventions for TR.
Project description:Extracorporeal membrane oxygenation (ECMO) is a vital mechanical circulatory support modality capable of restoring perfusion for the patient in circulatory failure. Despite increasing adoption of ECMO, there is incomplete understanding of its effects on systemic hemodynamics and how the vasculature responds to varying levels of continuous retrograde perfusion. To gain further insight into the complex ECMO:failing heart circulation, computational fluid dynamics simulations focused on perfusion distribution and hemodynamic flow patterns were conducted using a patient-derived aorta geometry. Three case scenarios were simulated: (1) healthy control; (2) 90% ECMO-derived perfusion to model profound heart failure; and, (3) 50% ECMO-derived perfusion to model the recovering heart. Fluid-structure interface simulations were performed to quantify systemic pressure and vascular deformation throughout the aorta over the cardiac cycle. ECMO support alters pressure distribution while decreasing shear stress. Insights derived from computational modeling may lead to better understanding of ECMO support and improved patient outcomes.
Project description:The endothelium in the coronary arteries is subject to wall shear stress and vessel wall strain, which influences the biology of the arterial wall. This study presents vessel-specific fluid-structure interaction (FSI) models of three coronary arteries, using directly measured experimental geometries and boundary conditions. FSI models are used to provide a more physiologically complete representation of vessel biomechanics, and have been extended to include coronary bending to investigate its effect on shear and strain. FSI both without- and with-bending resulted in significant changes in all computed shear stress metrics compared to CFD (p = 0.0001). Inclusion of bending within the FSI model produced highly significant changes in Time Averaged Wall Shear Stress (TAWSS) + 9.8% LAD, + 8.8% LCx, - 2.0% RCA; Oscillatory Shear Index (OSI) + 208% LAD, 0% LCx, + 2600% RCA; and transverse wall Shear Stress (tSS) + 180% LAD, + 150% LCx and + 200% RCA (all p < 0.0001). Vessel wall strain was homogenous in all directions without-bending but became highly anisotropic under bending. Changes in median cyclic strain magnitude were seen for all three vessels in every direction. Changes shown in the magnitude and distribution of shear stress and wall strain suggest that bending should be considered on a vessel-specific basis in analyses of coronary artery biomechanics.
Project description:Hemodynamics in aortic dissection (AD) is closely associated with the risk of aortic aneurysm, rupture, and malperfusion. Altered blood flow in patients with AD can lead to severe complications such as visceral malperfusion. In this study, we aimed to investigate the effect of cannulation flow on hemodynamics in AD using a fluid-structure interaction simulation. We developed a specific-idealized AD model that included an intimal tear in the descending thoracic aorta, a re-entry tear in the left iliac artery, and nine branches. Two different cannulation methods were tested: (1) axillary cannulation (AC) only through the brachiocephalic trunk and (2) combined axillary and femoral cannulation (AFC) through the brachiocephalic trunk and the right common iliac artery. AC was found to result in the development of a pressure difference between the true lumen and false lumen, owing to the difference in the flow rate through each lumen. This pressure difference collapsed the true lumen, disturbing blood flow to the celiac and superior mesenteric arteries. However, in AFC, the pressure levels between the two lumens were similar, and no collapse occurred. Moreover, the visceral flow was higher than that in AC. Lastly, the stiffness of the intimal flap affected the true lumen's collapse.
Project description:Purpose: This paper presents and clinically validates two algorithms for estimating intraocular pressure (IOP) and corneal material behavior using numerical models that consider the fluid-structure interaction between the cornea and the air-puff used in non-contact tonometry. Methods: A novel multi-physics fluid-structure interaction model of the air-puff test was employed in a parametric numerical study simulating human eyes under air-puff pressure with a wide range of central corneal thickness (CCT = 445-645 μm), curvature (R = 7.4-8.4 mm), material stiffness and IOP (10-25 mmHg). Models were internally loaded with IOP using a fluid cavity, then externally with air-puff loading simulated using a turbulent computational fluid dynamics model. Corneal dynamic response parameters were extracted and used in development of two algorithms for IOP and corneal material behavior; fIOP and fSSI, respectively. The two algorithms were validated against clinical corneal dynamic response parameters for 476 healthy participants. The predictions of IOP and corneal material behavior were tested on how they varied with CCT, R, and age. Results: The present study produced a biomechanically corrected estimation of intraocular pressure (fIOP) and a corneal material stiffness parameter or Stress-Strain Index (fSSI), both of which showed no significant correlation with R (p > 0.05) and CCT (p > 0.05). Further, fIOP had no significant correlation with age (p > 0.05), while fSSI was significantly correlated with age (p = 0.001), which was found earlier to be strongly correlated with material stiffness. Conclusion: The present study introduced two novel algorithms for estimating IOP and biomechanical material behavior of healthy corneas in-vivo. Consideration of the fluid structure interaction between the cornea and the air puff of non-contact tonometry in developing these algorithms led to improvements in performance compared with bIOP and SSI.
Project description:Organ-on-a-chip (OoC) technology has experienced exponential growth driven by the need for a better understanding of in-organ processes and the development of novel approaches. This paper investigates and compares the flow behavior and filling characteristics of two microfluidic liver-on-a-chip devices using Computational Fluid Dynamics (CFD) analysis and experimental cell culture growth based on the Huh7 cell line. The conducted computational analyses for the two chips showed that the elliptical chamber chip proposed herein offers improved flow and filling characteristics in comparison with the previously presented circular chamber chip. Huh7 hepatoma cells were cultured in the microfluidic devices for 24 h under static fluidic conditions and for 24 h with a flow rate of 3 μL·min-1. Biocompatibility, continuous flow, and biomarker studies showed cell attachment in the chips, confirming the cell viability and their consistent cell growth. The study successfully analyzed the fluid flow behavior, filling characteristics, and biocompatibility of liver-on-a-chip prototype devices, providing valuable insights to improve design and performance and advance alternative methods of in vitro testing.
Project description:This paper presents a new method for modeling the mechanics of the aortic valve and simulates its interaction with blood. As much as possible, the model construction is based on first principles, but such that the model is consistent with experimental observations. We require that tension in the leaflets must support a pressure, then derive a system of partial differential equations governing its mechanical equilibrium. The solution to these differential equations is referred to as the predicted loaded configuration; it includes the loaded leaflet geometry, fiber orientations and tensions needed to support the prescribed load. From this configuration, we derive a reference configuration and constitutive law. In fluid-structure interaction simulations with the immersed boundary method, the model seals reliably under physiological pressures and opens freely over multiple cardiac cycles. Further, model closure is robust to extreme hypo- and hypertensive pressures. Then, exploiting the unique features of this model construction, we conduct experiments on reference configurations, constitutive laws and gross morphology. These experiments suggest the following conclusions: (1) The loaded geometry, tensions and tangent moduli primarily determine model function. (2) Alterations to the reference configuration have little effect if the predicted loaded configuration is identical. (3) The leaflets must have sufficiently nonlinear material response to function over a variety of pressures. (4) Valve performance is highly sensitive to free edge length and leaflet height. These conclusions suggest appropriate gross morphology and material properties for the design of prosthetic aortic valves. In future studies, our aortic valve modeling framework can be used with patient-specific models of vascular or cardiac flow.