Structured tree impedance outflow boundary conditions for 3D lung simulations.

In this paper, we develop structured tree outflow boundary conditions for modeling the airflow in patient specific human lungs. The utilized structured tree is used to represent the nonimageable vessels beyond the 3D domain. The coupling of the two different scales (1D and 3D) employs a Dirichlet-Neumann approach. The simulations are performed under a variety of conditions such as light breathing and constant flow ventilation (which is characterized by very rapid acceleration and deceleration). All results show that the peripheral vessels significantly impact the pressure, however, the flow is relatively unaffected, reinforcing the fact that the majority of the lung impedance is due to the lower generations rather than the peripheral vessels. Furthermore, simulations of a hypothetical diseased lung (restricted flow in the superior left lobe) under mechanical ventilation show that the mean pressure at the outlets of the 3D domain is about 28% higher. This hypothetical model illustrates potential causes of volutrauma in the human lung and furthermore demonstrates how different clinical scenarios can be studied without the need to assume the unknown flow distribution into the downstream region.

Assessing Changes in Airflow and Energy Loss in a Progressive Tracheal Compression Before and After Surgical Correction.

The energy needed to drive airflow through the trachea normally constitutes a minor component of the work of breathing. However, with progressive tracheal compression, patient subjective symptoms can include severe breathing difficulties. Many patients suffer multiple respiratory co-morbidities and so it is important to assess compression effects when evaluating the need for surgery. This work describes the use of computational prediction to determine airflow resistance in compressed tracheal geometries reconstructed from a series of CT scans. Using energy flux analysis, the regions that contribute the most to airway resistance during inhalation are identified. The principal such region is where flow emerging from the zone of maximum constriction undergoes breakup and turbulent mixing. Secondary regions are also found below the tongue base and around the glottis, with overall airway resistance scaling nearly quadratically with flow rate. Since the anatomical extent of the imaged airway varied between scans-as commonly occurs with clinical data and when assessing reported differences between research studies-the effect of sub-glottic inflow truncation is considered. Analysis shows truncation alters the location of jet breakup and weakly influences the pattern of pressure recovery. Tests also show that placing a simple artificial glottis in the inflow to a truncated model can replicate patterns of energy loss in more extensive models, suggesting a means to assess sensitivity to domain truncation in tracheal airflow simulations.

Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points.

BACKGROUND AND AIMS: Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. METHODS: Evans' Blue dye-labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. RESULTS: Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p < 0.05), and the same pattern was seen when only the largest hotspots were considered. CONCLUSIONS: The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions.

SPH simulations of WBC adhesion to the endothelium: the role of haemodynamics and endothelial binding kinetics.

A multiscale Lagrangian particle solver introduced in our previous work is extended to model physiologically realistic near-wall cell dynamics. Three-dimensional simulation of particle trajectories is combined with realistic receptor-ligand adhesion behaviour to cover full cell interactions in the vicinity of the endothelium. The selected stochastic adhesion model, which is based on a Monte Carlo acceptance-rejection method, fits in our Lagrangian framework and does not compromise performance. Additionally, appropriate inflow/outflow boundary conditions are implemented for our SPH solver to enable realistic pulsatile flow simulation. The model is tested against in-vitro data from a 3D geometry with a stenosis and sudden expansion. In both steady and pulsatile flow conditions, results show close agreement with the experimental ones. Furthermore we demonstrate, in agreement with experimental observations, that haemodynamics alone does not account for adhesion of white blood cells, in this case U937 monocytic human cells. Our findings suggest that the current framework is fully capable of modelling cell dynamics in large arteries in a realistic and efficient manner.

A multiscale SPH particle model of the near-wall dynamics of leukocytes in flow.

A novel multiscale Lagrangian particle solver based on SPH is developed with the intended application of leukocyte transport in large arteries. In such arteries, the transport of leukocytes and red blood cells can be divided into two distinct regions: the bulk flow and the near-wall region. In the bulk flow, the transport can be modeled on a continuum basis as the transport of passive scalar concentrations. Whereas in the near-wall region, specific particle tracking of the leukocytes is required and lubrication forces need to be separately taken into account. Because of large separation of spatio-temporal scales involved in the problem, simulations of red blood cells and leukocytes are handled separately. In order to take the exchange of leukocytes between the bulk fluid and the near-wall region into account, solutions are communicated through coupling of conserved quantities at the interface between these regions. Because the particle tracking is limited to those leukocytes lying in the near-wall region only, our approach brings considerable speedup to the simulation of leukocyte circulation in a test geometry of a backward-facing step, which encompasses many flow features observed in vivo.

A novel formulation for Neumann inflow boundary conditions in biomechanics.

Neumann boundary conditions prescribing the total momentum flux at inflow boundaries of biomechanical problems are proposed in this study. This approach enables the simultaneous application of velocity/flow rate and pressure curves at inflow boundaries. As the basic numerical method, a residual-based variational multiscale (or stabilized) finite element method is presented. The focus of the numerical examples in this work is on respiratory flows with complete flow reversals. However, the proposed formulation is just as well suited for cardiovascular flow problems with partial retrograde flow. Instabilities, which were reported for such problems in the literature, are resolved by the present approach without requiring the additional consideration of a Lagrange multiplier technique. The suitability of the approach is demonstrated for two respiratory flow examples, a rather simple tube and complex tracheobronchial airways (up to the fourth generation, segmented from end-expiratory CT images). For the latter example, the boundary conditions are generated from mechanical ventilation data obtained from an intensive care unit patient suffering from acute lung injury. For the tube, analytical pressure profiles can be replicated, and for the tracheobronchial airways, a correct distribution of the prescribed total momentum flux at the inflow boundary into velocity and pressure part is observed.

ATP transport in saccular cerebral aneurysms at arterial bends.

ATP acts as an extracellular signaling molecule in purinergic signaling that regulates vascular tone. ATP binds purinergic P2 nucleotide receptors on endothelial cells. Understanding the mass transport of ATP to endothelial cells by blood flow is thus important to predict functional changes in aneurysmal walls. While some clinical observations indicate a difference of wall pathology between ruptured and unruptured aneurysms, no study has focused on the mass transport in aneurysms. We investigated the characteristics of ATP concentration at aneurysmal wall using a numerical model of ATP transport in aneurysms formed at arterial bends. The magnitude of ATP concentration at the aneurysmal wall was significantly smaller than that at the arterial wall. In particular, significantly low concentration was predicted at the proximal side of the aneurysmal sac. A strong correlation was revealed between the inflow flux at the aneurysmal neck and the resultant concentration at the aneurysmal wall.

Computer model of nucleotide transport in a realistic porcine aortic trifurcation.

Adenosine triphosphate (ATP) is a ubiquitous blood borne agonist which is responsible for the regulation of vascular tone via purinogenic signalling pathways. The present study models the transport of ATP in a realistic porcine aortic trifurcation, which includes multiple branches and bifurcations. The focus of the present study is understanding how pulsatile flow effects mass transfer, observing both mean and transient variations. Unlike in the many idealized models which model transport of low diffusion coefficient species, the realistic geometry leads to very different mass transfer characteristics. These include spiral patterns in the distribution of low concentration fluid. Furthermore, the mean ATP distribution was found to be elevated compared with the steady state; this is attributed to the effects of convective mixing. The results strongly implicate that under certain conditions mass transport in pulsatile flow exhibits different hydrolysis characteristics at the endothelium compared with steady state. Transient variations throughout the the cardiac cycle were found to be small. This small transient response is primarily due to low ATP diffusivity.

Effects of arterial bifurcation geometry on nucleotide concentration at the endothelium.

A mathematical and computational analysis of nucleotide concentration for a two-dimensional artery bifurcation has been developed. This region of the vasculature is known to be exposed to spatially varying wall shear stress (WSS), hence the variation of adenosine nucleotides is of interest. A previously derived similarity solution for mass transport in blood boundary layers for arbitrary wall shear stress function has been used. For the analytical model, the geometric condition has been incorporated into the system using the theory for flow past a wedge. As the bifurcation angle varies different characteristics are exhibited, such as maxima in ADP concentration and the existence of a low wall shear stress region around the stagnation point, for large angles. In the limiting case of two-dimensional stagnation point flow the concentration was constant throughout the domain length. The computational simulations provided a more detailed understanding into how nucleotides vary. Similarities existed between the two solution methods in the vicinity of the stagnation point, but deviated as the fully developed condition prevailed. Additionally, the effect of pulsatile flow has been included, leading to considerable gradients in wall shear stress, both temporal and spatial. However, the resulting nucleotide concentration is determined by the time-averaged wall shear stress. The effects of flow-induced ATP release have also been included, leading to significant changes in ATP concentration. Under rapid release, the concentration at the surface increased relative to the bulk concentration.