Purpose: The purpose of this study is to assess the importance of non-Newtonian rheological models on blood flow in the human thoracic aorta. Methods: The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models (using constant hematocrit) was assessed with respect to (i) magnitude and deviation of the viscosity relative to a reference value (the Newtonian case); (ii) wall shear stress (WSS) and its time derivative; (iii) common WSS-related indicators, OSI, TAWSS and RRT; (iv) relative volume and surface-based retrograde flow; and (v) the impact of rheological models on the transport of small particles in the thoracic aorta. Results: The time-dependent flow in the thoracic aorta implies relatively large variations in the instantaneous WSS, due to variations in the instantaneous viscosity by as much as an order of magnitude. The largest effect was observed for low shear rates (tens s-1). The different viscosity models had a small impact in terms of time- and spaced-averaged quantities. The significance of the rheological models was clearly demonstrated in the instantaneous WSS, for the space-averaged WSS (about 10%) and the corresponding temporal derivative of WSS (up to 20%). The longer-term accumulated effect of the rheological model was observed for the transport of spherical particles of 2 mm and 2 mm in diameter (density of 1200 kg/m3). Large particles' total residence time in the brachiocephalic artery was 60% longer compared to the smaller particles. For the left common carotid artery, the opposite was observed: the smaller particles resided considerably longer than their larger counterparts. Conclusions: The dependence on the non-Newtonian properties of blood is mostly important at low shear regions (near walls, stagnation regions). Time- and space-averaging parameters of interest reduce the impact of the rheological model and may thereby lead to under-estimation of viscous effects. The rheological model affects the local WSS and its temporal derivative. In addition, the transport of small particles includes the accumulated effect of the blood rheological model as the several forces (e.g., drag, added mass and lift) acting on the particles are viscosity dependent. Mass transport is an essential factor for the development of pathologies in the arterial wall, implying that rheological models are important for assessing such risks.

The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.

Aim: The first dedicated neonatal continuous positive airway pressure (CPAP) device using variable flow was the Infant Flow. The system was pressure stable with a low resistance to breathing. The aim of this study was to describe the flow and function of the Infant Flow geometry using simulated breathing and computational fluid dynamics. Method: The original Infant Flow geometry was used with simulated term infant breathing at three levels of CPAP. The large eddy simulation methodology was applied in combination with the WALE sub-grid scale model. Results: The simulation fully resolved the flow phenomena in the Infant Flow geometry. The main flow feature during inspiration was support by gas entrainment and mixing. During expiration, the jet deflected towards the outlet with unstable impingement of the jet at the opposing edge. Conclusion: The proposed mechanism has previously been based on theoretical reasoning, and our results present the first detailed description of the Infant Flow. The pressure stability was based on a jet supporting inspiration by gas entrainment and then being deflected during exhalation. This confirmed previously assumed principles of function and flows within the geometry and provided a base for further developments. 

Patient specific (PS) blood flow studies have become popular in recent years but have thus far had limited clinical impact. This is possibly due to uncertainties and errors in the underlying models and simulations set-up. This study focuses on the sensitivity of simulation results due to in- and outflow boundary conditions (BC:s). Nine different inlet- and seven different outlet BC:s were applied to two variants of a healthy subject’s thoracic aorta. Temporal development of the flow is essential for the formation and development of helical/spiralling flow where the commonly observed clockwise helical motion may change direction during the heart-cycle. The sensitivity to temporal and spatial variations in the inlet conditions is significant both when expressed in terms of mean and maximal wall shear stress (WSS) and its different averaged variables, e.g. Time-Averaged WSS (TAWSS), Oscillating Shear Index (OSI) and Relative Residence Time (RRT). The simulation results are highly sensitive to BC. For example, the maximal WSS may vary over 3 orders of magnitude (1 to 1000 Pa) depending on particular combinations of BC:s. Moreover, certain formulations of outlet boundary conditions may be inconsistent with the computed flow field if the underlying assumptions of the space-time dependence are violated. The results of this study show that CFD simulations can reveal flow details that can enhance understanding of blood flows. However, the results also demonstrate the potential difficulties in mimicking blood flow in clinical situations.

Patient specific based simulation of blood flows in arteries has been proposed as a future approach for better diagnostics and treatment of arterial diseases. The outcome of theoretical simulations strongly depends on the accuracy in describing the problem (the geometry, material properties of the artery and of the blood, flow conditions and the boundary conditions). In this study, the uncertainties associated with the approach for a priori assessment of reconstructive surgery of stenoted arteries are investigated. It is shown that strong curvature in the reconstructed artery leads to large spatial- and temporal-peaks in the wall shear-stress. Such peaks can be removed by appropriate reconstruction that also handles the post-stenotic dilatation of the artery. Moreover, it is shown that the effects of the segmentation approach can be equally important as the effects of using advanced rheological models. This fact has not been recognized in the literature up to this point, making patient specific simulations potentially less reliable.

Blood clot formation can be initiated by local flow conditions where regions of high shear and long residence time regions, such as flow separation and stagnation, have been identified as risk factors. This study highlights coherent structures,some of which not yet considered in the literature that may contribute to blood clot formation in the ECMO (Extra Corporeal Membrane Oxygenator) circuit. The centrifugal ECMO pump investigated in this study is compact and delivers adequate volume of blood with relatively high pressure in order to compensate for the large pressure drop in the membrane oxygenator. These requirements lead to regions with high shear in several different parts of the pump. In the narrow gap between the pump house and the impeller body (the magnet) a Taylor-Couette-like flow is observed with azimuthally aligned wavy vortices, which are also pushed towards the bottom of the pump-house by the flow generated by the blades. At the bottom gap between the impeller house and the pump house one finds spiraling flow structures, due to the rotation of the former structure. Separation bubbles are found near the tongue of the pump and at the lee sides of the blades. Such vortical structures have in literature been identified as regions where platelets may be activated whereby clots may develop.

Two platelet activation models were studied with respect to uncertainties of model parameters and variables. The sensitivity was assessed using two direct/deterministic approaches as well as the statistical Monte Carlo method. The first two, are linear in character whereas the latter is non-linear. The platelet activation models were applied on platelets moving within an extracorporeal centrifugal blood pump. The phenomenological, Lagrangian stress- and time-based power law-based models under consideration, have experimentally calibrated parameters and the stress expressed in a scalar form. The sensitivity of the model with respect to model parameters and the expression of the scalar stress was examined focusing on a smaller group of platelets associated with an elevated risk of activation. The results showed a high disparity between the models in terms of platelet activation state, found to depend on the platelets’ trajectory in the pump and the expression used for the scalar stress. Monte Carlo statistics was applied to the platelets at risk for activation and not to the entire platelet population. The method reveals the non-linear sensitivity of the activation models. The results imply that power-law based models have a restricted range of validity. The conclusions of this study apply to both platelet activation and hemolysis models.

Pulsatile flow in the abdominal aorta and the renal arteries of three patients was studied numerically. Two of the patients had renal artery stenosis. The aim of the study was to assess the use of four types of indicators for determining the risk of new stenosis after revascularization of the affected arteries. The four indicators considered include the time averaged wall shear stress (TAWSS), the oscillatory shear index (OSI), the relative reference time (RRT) and a power law model based in platelet activation modeling but applied to the endothelium, named endothelium activation indicator (EAI). The results show that the indicators can detect the existing stenosis but are less successful in the revascularized cases. The TAWSS and, more clearly, the EAI approach seem to be better in predicting the risk for stenosis relapse at the original location and close to the post-stenotic dilatation. The shortcomings of the respective indicators are discussed along with potential improvements to endothelial activation modeling and its use as an indicator for risks of restenosis.

Extracorporeal membrane oxygenation (ECMO) is used for rescue in severe respiratory and/or circulatory failure. The patient's blood is pumped over artificial surfaces in the ECMO circuit. A platelet activation model was applied to study the potential thrombogenicity of ECMO circuit components: the centrifugal blood pump, cannulae, and tubing connectors. Based on the accumulated effect of the scalar form of the stress acting on the platelet over time, the activation model enables assessment of platelet activation and pinpoints regions of elevated activation risk in a component. Numerical simulations of the flow in different components of the ECMO circuit was carried out where the activation level is a function of the impact of local stress and its history along the path that the platelets follow. The results showed that the pump carried the largest risk for platelet activation followed by the reinfusion cannula and lastly the connectors. Pump thrombogenicity was mainly due to long residence time and high shear-rate while the connector showed a high level of non-stationary shear-rate that in turn may contribute to the formation of aggregates through direct platelet activation or through high shear-rate modulation of the vWF multimers.