Explore the vast range of titles available.

Coronary flow is different from the flow in other parts of the arterial system because it is influenced by the contraction and relaxation of the heart. To model coronary flow realistically, the compressive force of the heart acting on the coronary vessels needs to be included. In this study, we developed a method that predicts coronary flow and pressure of three-dimensional epicardial coronary arteries by considering models of the heart and arterial system and the interactions between the two models. For each coronary outlet, a lumped parameter coronary vascular bed model was assigned to represent the impedance of the downstream coronary vascular networks absent in the computational domain. The intramyocardial pressure was represented with either the left or right ventricular pressure depending on the location of the coronary arteries. The left and right ventricular pressure were solved from the lumped parameter heart models coupled to a closed loop system comprising a three-dimensional model of the aorta, three-element Windkessel models of the rest of the systemic circulation and the pulmonary circulation, and lumped parameter models for the left and right sides of the heart. The computed coronary flow and pressure and the aortic flow and pressure waveforms were realistic as compared to literature data.

Aortic flow and pressure result from the interactions between the heart and arterial system. In this work, we considered these interactions by utilizing a lumped parameter heart model as an inflow boundary condition for three-dimensional finite element simulations of aortic blood flow and vessel wall dynamics. The ventricular pressure–volume behavior of the lumped parameter heart model is approximated using a time varying elastance function scaled from a normalized elastance function. When the aortic valve is open, the coupled multidomain method is used to strongly couple the lumped parameter heart model and three-dimensional arterial models and compute ventricular volume, ventricular pressure, aortic flow, and aortic pressure. The shape of the velocity profiles of the inlet boundary and the outlet boundaries that experience retrograde flow are constrained to achieve a robust algorithm. When the aortic valve is closed, the inflow boundary condition is switched to a zero velocity Dirichlet condition. With this method, we obtain physiologically realistic aortic flow and pressure waveforms. We demonstrate this method in a patient-specific model of a normal human thoracic aorta under rest and exercise conditions and an aortic coarctation model under pre- and post-interventions.

This paper is motivated by the modeling of blood flows through the beating myocardium, namely cardiac perfusion. As in other works, perfusion is modeled here as a flow through a poroelastic medium. The main contribution of this study is the derivation of a general poroelastic model valid for a nearly incompressible medium which experiences finite deformations. A numerical procedure is proposed to iteratively solve the porous flow and the nonlinear poroviscoelastic problems. Three-dimensional numerical experiments are presented to illustrate the model. The first test cases consist of typical poroelastic configurations: swelling and complete drainage. Finally, a simulation of cardiac perfusion is presented in an idealized left ventricle embedded with active fibers. Results show the complex temporal and spatial interactions of the muscle and blood, reproducing several key phenomena observed in cardiac perfusion.

The objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases-to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes.

Anatomical and physiological changes alter airflow characteristics and aerosol distribution in the developing lung. Correlation between age and aerosol dosimetry is needed, specifically because youth are more susceptible to medication side effects. In this study, we estimate aerosol dosages (particle diameters of 1, 3, and 5  μ m) in a 3 month-old infant, a 6 year-old child, and a 36 year-old adult by performing whole lung subject-specific particle simulations throughout respiration. For 3  μ m diameter particles we estimate total deposition as 88, 73, and 66 % and the conducting versus respiratory deposition ratios as 4.0, 0.5, and 0.4 for the infant, child, and adult, respectively. Due to their lower tidal volumes and functional residual capacities the deposited mass is smaller while the tissue concentrations are larger in the infant and child subjects, compared to the adult. Furthermore, we find that dose cannot be predicted by simply scaling by tidal volumes. These results highlight the need for additional clinical and computational studies that investigate the efficiency of treatment, while optimizing dosage levels in order to alleviate side effects, in youth.

We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS) of SK-MES-1 cells, a non-small cell lung cancer (NSCLC) cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM), cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions. We thus ultimately arrive at a model that mimics the MCTS growth under multiple conditions to a great extent. Interestingly, the final model, is a minimal model capable of explaining all data simultaneously in the sense, that the number of mechanisms it contains is sufficient to explain the data and missing out any of its mechanisms did not permit fit between all data and the model within physiological parameter ranges. Nevertheless, compared to earlier models it is quite complex i.e., it includes a wide range of mechanisms discussed in biological literature. In this model, the cells lacking oxygen switch from aerobe to anaerobe glycolysis and produce lactate. Too high concentrations of lactate or too low concentrations of ATP promote cell death. Only if the extracellular matrix density overcomes a certain threshold, cells are able to enter the cell cycle. Dying cells produce a diffusive growth inhibitor. Missing out the spatial information would not permit to infer the mechanisms at work. Our findings suggest that this iterative data integration together with intermediate model sensitivity analysis at each model development stage, provide a promising strategy to infer predictive yet minimal (in the above sense) quantitative models of tumor growth, as prospectively of other tissue organization processes. Importantly, calibrating the model with two nutriment-rich growth conditions, the outcome for two nutriment-poor growth conditions could be predicted. As the final model is however quite complex, incorporating many mechanisms, space, time, and stochastic processes, parameter identification is a challenge. This calls for more efficient strategies of imaging and image analysis, as well as of parameter identification in stochastic agent-based simulations.

The liver function may be degraded after partial liver ablation surgery. Adverse liver hemodynamics have been shown to be associated to liver failure. The link between these hemodynamics changes and ablation size is however poorly understood. This article proposes to explain with a closed-loop lumped model the hemodynamics changes observed during twelve surgeries in pigs. The portal venous tree is modeled with a pressure-dependent variable resistor. The variables measured, before liver ablation, are used to tune the model parameters. Then, the liver partial ablation is simulated with the model and the simulated pressures and flows are compared with post-operative measurements. Fluid infusion and blood losses occur during the surgery. The closed-loop model presented accounts for these blood volume changes. Moreover, the impact of blood volume changes and the liver lobe mass estimations on the simulated variables is studied. The typical increase of portal pressure, increase of liver pressure loss, slight decrease of portal flow and major decrease in arterial flow are quantitatively captured by the model for a 75% hepatectomy. It appears that the 75% decrease in hepatic arterial flow can be explained by the resistance increase induced by the surgery, and that no hepatic arterial buffer response (HABR) mechanism is needed to account for this change. The different post-operative states, observed in experiments, are reproduced with the proposed model. Thus, an explanation for inter-subjects post-operative variability is proposed. The presented framework can easily be adapted to other species circulations and to different pathologies for clinical hepatic applications.