Examining the universality of the hemolysis power law model from simulations of the FDA nozzle using calibrated model coefficients.

Computational fluid dynamics (CFD) is widely used to predict mechanical hemolysis in medical devices. The most popular hemolysis model is the stress-based power law model that is based on an empirical correlation between hemoglobin release from red blood cells (RBCs) and the magnitude of flow-induced stress and exposure time. Empirical coefficients are traditionally calibrated using data from experiments in simplified Couette-type blood-shearing devices with uniform-shear laminar flow and well-defined exposure times. Use of such idealized coefficients in simulations of real medical devices with complex hemodynamics is thought to be a primary reason for the historical inaccuracy of absolute hemolysis predictions using the power law model. Craven et al. (Biomech Model Mechanobiol 18:1005-1030, 2019) recently developed a CFD-based Kriging surrogate modeling approach for calibrating empirical coefficients in real devices that could potentially be used to more accurately predict absolute hemolysis. In this study, we use the FDA benchmark nozzle to investigate whether utilizing such calibrated coefficients improves the predictive accuracy of the standard Eulerian power law model. We first demonstrate the credibility of our CFD flow simulations by comparing with particle image velocimetry measurements. We then perform hemolysis simulations and compare the results with in vitro experiments. Importantly, the simulations use coefficients calibrated for the flow of a suspension of bovine RBCs through a small capillary tube, which is relatively comparable to the flow of bovine blood through the FDA nozzle. The results show that the CFD predictions of relative hemolysis in the FDA nozzle are reasonably accurate. The absolute predictions are, however, highly inaccurate with modified index of hemolysis values from CFD in error by roughly three orders of magnitude compared with the experiments, despite using calibrated model coefficients from a relatively similar geometry. We rigorously examine the reasons for the inaccuracy that include differences in the flow conditions in the hemolytic regions of each device and the lack of universality of the hemolysis power law model that is entirely empirical. Thus, while the capability to predict relative hemolysis is valuable for product development, further improvements are needed before the power law model can be relied upon to accurately predict the absolute hemolytic potential of a medical device.

Clot embolization studies and computational framework for embolization in a canonical tube model.

Despite recent advances in the development of computational methods of modeling thrombosis, relatively little effort has been made in developing methods of modeling blood clot embolization. Such a model would provide substantially greater understanding of the mechanics of embolization, as in-vitro and in-vivo characterization of embolization is difficult. Here, a method of computationally simulating embolization is developed. Experiments are performed of blood clots formed in a polycarbonate tube, where phosphate-buffered saline is run through the tube at increasing flow rates until the clot embolizes. The experiments revealed embolization can be initiated by leading edge and trailing edge detachment or by non-uniform detachment. Stress-relaxation experiments are also performed to establish values of constitutive parameters for subsequent simulations. The embolization in the tube is reproduced in silico using a multiphase volume-of-fluid approach, where the clot is modeled as viscoelastic. By varying the constitutive parameters at the wall, embolization can be reproduced in-silico at varying flow rates, and a range of constitutive parameters fitting the experiments is reported. Here, the leading edge embolization is simulated at flow rates consistent with the experiments demonstrating excellent agreement in this specific behavior.

Toward modeling thrombosis and thromboembolism in laminar and turbulent flow regimes.

Thrombosis and thromboembolism are deadly risk factors in blood-contacting biomedical devices, and in-silico models of thrombosis are attractive tools to understand the mechanics of these processes, though the simulation of thromboembolism remains underdeveloped. The purpose of this study is to modify an existing computational thrombosis model to allow for thromboembolism and to investigate the behavior of the modified model at a range of flow rates. The new and existing models are observed to lead to similar predictions of thrombosis in a canonical backward-facing step geometry across flow rates, and neither model predicts thrombosis in a turbulent flow. Simulations are performed by increasing flow rates in the case of a clot formed at lower flow to induce embolization. While embolization is observed, most of the clot breakdown is by shear rather than by breakup and subsequent transport of clotted material, and further work is required in the formulation and validation of embolization. This model provides a framework to further investigate thromboembolization.

Computational Investigation of Anastomosis Options of a Right-Heart Pump to Patient Specific Pulmonary Arteries.

Patients with Fontan circulation have increased risk of heart failure, but are not always candidates for heart transplant, leading to the development of the subpulmonic Penn State Fontan Circulation Assist Device. The aim of this study was to use patient-specific computational fluid dynamics simulations to evaluate anastomosis options for implanting this device. Simulations were performed of the pre-surgical anatomy as well as four surgical options: a T-junction and three Y-grafts. Cases were evaluated based on several fluid-dynamic quantities. The impact of imbalanced left-right pulmonary flow distribution was also investigated. Results showed that a 12-mm Y-graft was the most energy efficient. However, an 8-mm graft showed more favorable wall shear stress distribution, indicating lower risk of thrombosis and endothelial damage. The 8-mm Y-grafts also showed a more balanced pulmonary flow split, and lower residence time, also indicating lower thrombosis risk. The relative performance of the surgical options was largely unchanged whether or not the pulmonary vascular resistance remained imbalanced post-implantation.

Refining a numerical model for device-induced thrombosis and investigating the effects of non-Newtonian blood models.

Thrombosis is one of the main causes of failure in device implantation. Computational thrombosis simulation is a convenient approach to evaluate the risk of thrombosis for a device. However, thrombosis is a complicated process involving multiple species and reactions. Application of a macroscopic, single-scale computational model for device-induced thrombosis is a cost-effective approach. The current study has refined an existing thrombosis model, which simulated thrombosis by tracing four species in blood: non-activated platelets, activated platelets, surface adherent platelets, and ADP. Platelets are activated mechanically by shear stress, and chemically by ADP. Platelet adhesion occurs on surfaces with low wall shear stress with platelet aggregation inhibited in regions of high shear stress. The study improves the existing thrombosis model by: 1) Modifying the chemical platelet activation function so that ADP activates platelets; 2) Modifying the function describing thrombus deposition and growth to distinguish between thrombus deposition on wall surfaces and thrombus growth on existing thrombus surfaces; 3) Modifying the thrombus breakdown function to allow for thrombus breakdown by shear stress; 4) Modeling blood flow as non-Newtonian. The results show that the inclusion of ADP and the use of a non-Newtonian model improve agreement with experimental data.

Large-Eddy Simulations of Flow in the FDA Benchmark Nozzle Geometry to Predict Hemolysis.

PURPOSE: Modeling of hemolysis due to fluid stresses faces significant methodological challenges, particularly in geometries with turbulence or complex flow patterns. It is currently unclear how existing phenomenological blood-damage models based on laminar viscous stresses can be implemented into turbulent computational fluid dynamics simulations. The aim of this work is to generalize the existing laminar models to turbulent flows based on first principles, and validate this generalization with existing experimental data. METHODS: A novel analytical and numerical framework for the simulation of flow-induced hemolysis based on the intermittency-corrected turbulent viscous shear stress (ICTVSS) is introduced. The proposed large-eddy simulation framework is able to seamlessly transition from laminar to turbulent conditions in a single flow domain by linking laminar shear stresses to dissipation of mechanical energy, accounting for intermittency in turbulent dissipation, and relying on existing power-law hemolysis models. Simulations are run to reproduce previously published hemolysis data with bovine blood in a benchmark geometry. Two sets of experimental data are relied upon to tune power-law parameters and justify that tuning. The first presents hemolysis measurements in a simple laminar flow, and the second is hemolysis in turbulent flow through the FDA benchmark nozzle. Validation is performed by simulation of blood injected into a turbulent jet of phosphate-buffered saline, with modifications made to account for the local concentration of blood. RESULTS: Hemolysis predictions are found to be very sensitive to power-law parameters in the turbulent case, though a set of parameters is presented that both matches the turbulent data and is well-justified by the laminar data. The model is shown to be able to predict the general behavior of hemolysis in a second turbulent case. Results suggest that wall shear may play a dominant role in most cases. CONCLUSION: The ICTVSS framework of generalizing laminar power-law models to turbulent flows shows promise, but would benefit from further numerical validation and carefully designed experiments.

Towards uncovering the structure of power fluctuations of wind farms.

The structure of the turbulence-driven power fluctuations in a wind farm is fundamentally described from basic concepts. A derived tuning-free model, supported with experiments, reveals the underlying spectral content of the power fluctuations of a wind farm. It contains two power-law trends and oscillations in the relatively low- and high-frequency ranges. The former is mostly due to the turbulent interaction between the flow and the turbine properties, whereas the latter is due to the advection between turbine pairs. The spectral wind-farm scale power fluctuations Φ_{P} exhibit a power-law decay proportional to f^{-5/3-2} in the region corresponding to the turbulence inertial subrange and at relatively large scales, Φ_{P}∼f^{-2}. Due to the advection and turbulent diffusion of large-scale structures, a spectral oscillation exists with the product of a sinusoidal behavior and an exponential decay in the frequency domain.