At test condition 5, the outlet jet in the exit diffuser was skewed toward the outer wall in all four data sets (Figures 5 and 6B). This asymmetry created a large recirculation region near the inner wall of the pump diffuser (see Video, Supplemental Digital Content, http://links.lww.com/ASAIO/A129, which demonstrates the exit jet and recirculating flow pattern). For flow rates above 4.5 L/min (i.e., conditions 4, 5, and 6), the exit jet angled toward the outer wall for both pump speeds (2500 and 3500 rpm). However, for Q = 2.5 L/min (test conditions 1 and 2), the jet was skewed toward the inner wall of the exit diffuser.
Computational fluid dynamics simulations of the blood pump model.
Where noted, results that were deemed to be unreliable due to suspected participant reporting errors were not included in the present analyses. For the CFD pressure head predictions (n = 19–21 at each test condition), 57% were within the one standard deviation bounds defined by the pressure measurements made during the hemolysis and PIV experiments at each test condition (Figure 4B). The variability in CFD predictions of pressure head was greatest for conditions 3–6.
For this summary, only the velocity results for 12 of the 14 submitted steady-state simulations are presented because of suspected reporting errors in two submissions. Comparison of the interpolated participant velocity field data in the blade passage plane for condition 5 showed that the steady-state CFD simulations qualitatively predicted similar flow patterns in the pump, but highly varied flow patterns in the diffuser (Figure 7). In most of the CFD submissions, the maximum velocities occurred around the front, outer, or trailing edge of the impeller tip with values slightly greater than the impeller tip speed (9.52 m/s, r = 26 mm). Subtle differences in the CFD-predicted flow patterns for a few participants included small regions of low-speed flow in the vicinity of the cutwater (Figure 7E, H, I, and K) and along the upper wall of the pump housing (Figure 7B and G).
All participants predicted separated flow in the diffuser, but the location of the exit jet and recirculation zone varied. Three submissions (Figure 7A, K, and L) predicted that the flow attaches to the inner wall of the diffuser, whereas two participants (Figure 7C and F) predicted that the jet forms roughly in the center of the diffuser. The other seven steady-state CFD simulations shown in Figure 7 all predicted skewed flow toward the outer wall of the diffuser, which is more consistent with the PIV experimental observations (Figure 5).
Within the rotating region of the pump, the velocity magnitude predicted by the steady-state CFD submissions compared reasonably well with the PIV data (Figure 6A and C). At x = 0.035 m within the diffuser, however, only two of the steady-state CFD submissions accurately predicted the location and magnitude of the detached jet when compared with the experiments (Figure 6B and D). A preliminary analysis indicates that this may be at least partially due to the same choice of turbulence model in both submissions (realizable k–ε).
Hemolysis testing of the blood pump model.
The blood used in the tests had an adjusted hematocrit of 36 ± 1%, a viscosity of 3.4 ± 0.5 cP (measured at a shear rate of 500 s−1 at 25°C), and a density of 1.03 ± 0.01 g/ml, which matched the blood parameters used by the CFD modelers. During the 2 hour hemolysis tests, the loop blood temperature remained at 25 ± 1°C, and the temperature of the shaft blood seal gland stabilized at 27–29°C.
Hemolysis generation occurred at a constant rate over time (i.e., for pfHb vs. time, 88% of all hemolysis tests had r 2 > 0.95). Figure 8 shows the in vitro pfHb results for the blood pump model at the six operating points. Of the 96 total pump hemolysis tests (six test conditions with 16 repeats each), a total of four single outliers were identified at four separate test conditions. Hemolysis levels were statistically different between the two extreme test conditions and most of the other test conditions (by ANOVA test after removal of outliers). Specifically, condition 1 was statistically different from conditions 3–6, and condition 6 was statistically different from all of the other conditions. Levels of hemolysis in the clinical control blood pump loops (data not shown) were significantly lower at each test condition as compared to the benchmark blood pump model (ANOVA, p < 0.05).
Computational fluid dynamics predictions of hemolysis were reported only in 8 of the 24 blood pump submissions. Because of suspected reporting errors by three participants, absolute levels of generated plasma hemoglobin for direct comparison to the experimental hemolysis results are not presented. Instead, the participant-provided relative hemolysis values are compared with the experimentally calculated RHI results. As shown in Figure 9, the computationally derived values of RHI from the eight participants vary widely, even though seven of the eight participants used a shear stress–based power-law model.4,16,29
Computational fluid dynamics modeling is a valuable tool in the design stages of medical device development, but the lack of standard procedures for demonstrating the validity of complex flow field simulations and blood damage predictions limits its use in risk-based evaluations. This article provides an overview of our collaborative research efforts to contribute publicly available data to help improve the use of CFD as a credible tool in the safety evaluation of blood-contacting medical devices. The main goals of our project are to: 1) establish a set of benchmark models that are representative of cardiovascular medical devices and provide experimental data (for velocity, pressure, shear stresses, and hemolysis) which could be used for validating CFD practices; 2) understand current practices of applying CFD to medical devices by facilitating open CFD challenges; 3) collaboratively develop standards for applying CFD in the regulatory evaluation process for medical devices; and 4) promote the further development of methods to reliably predict blood damage (e.g., hemolysis, thrombosis, platelet activation).
Two benchmark flow models, a nozzle and a centrifugal blood pump, were characterized under varying flow conditions using PIV analysis (to measure the velocity, shear stress, and pressure fields) and hemolysis testing (to determine blood damage potential) for comparison to computational predictions. Experiments were performed in multiple laboratories to establish ranges of measurement error and to make the results as robust as possible. All details about the benchmark models, the CFD simulation challenges, and the available experimental results can be found at https://fdacfd.nci.nih.gov.30
Analysis of the nozzle benchmark model revealed that CFD predictions of the velocity field in even a simple, steady-flow model may present challenges, as many of the simulations were unable to accurately predict velocities and shear stresses in the recirculation zones downstream of the sudden expansion.9 Moreover, this study also demonstrated the modeling issues associated with accurately predicting transition from laminar to turbulent flow, which often occurs in medical devices.4,10,11 Based on the nozzle analysis, a list of 21 “CFD Best Practice” guidelines were developed that include justifying the choice of a turbulence model and its parameters, identifying and quantifying the necessary boundary and initial conditions, confirming numerical convergence, performing a grid refinement study, and validating the simulation to reliable experimental data obtained in similar types of models using quantitative measures.9,10 These and other important considerations for verification and validation of computational modeling used to evaluate medical devices are described in an FDA Guidance Document12 and a draft American Society of Mechanical Engineers (ASME) standard.14
The significance of this project is further exemplified by the use of our interlaboratory PIV data for the nozzle model by multiple groups as a benchmark data set for validating and improving in-house, open-source, and commercial CFD solvers. In the laminar flow regime, White et al.31 used this model to assess the Lattice Boltzmann method, and Trias et al.32 concluded that treating the blood as Newtonian instead of a non-Newtonian fluid led to an underestimation of the hemolysis levels. Several studies have also used the nozzle PIV data to validate advanced turbulence models. Fabritious et al.33 used a genetic algorithm-based optimization method to derive improved model coefficients for some of the most common RANS turbulence models, including k–ε, k–ω, and Spalart–Allmaras. Janiga et al.34 used the PIV data at Re = 6500 to show that their large eddy simulation (LES) model predicted the temporally averaged flow velocities better than commonly used RANS models. Zmijanovic et al.35 showed that the downstream jet breakdown location for transitional flow through the nozzle was strongly affected by the solver numerics (grid size, temporal integration scheme, time step) and low-level inlet perturbations. Bhushan et al.,36 Delorme et al.,37 and Passerini et al.38 used the data to validate their hybrid RANS/LES, LES/immersed boundary method, and direct numerical simulation solvers, respectively.
Subsequent experimental studies have also been performed on the nozzle model to more fully characterize the flow fields for CFD validation. To resolve flow regions with large velocity ranges and gradients (such as the region downstream of the nozzle throat where a high-velocity jet is bounded by recirculation zones at the walls), Raben et al.3 used increased PIV image spatial resolution, ensemble correlation, dynamic range enhancement, and phase correlations to increase signal-to-noise ratios and measurement accuracy compared with the original multi-laboratory PIV measurements. As local velocity uncertainty was found to vary greatly and depend largely on local conditions such as particle seeding, velocity gradients, and particle displacements, suggestions for improving PIV measurement practices in medical device evaluations have also been proposed.3,24 Recently, high spatial resolution two-component laser Doppler velocimetry (LDV) measurements in the jet shear layer downstream of the nozzle throat at Re = 5000 showed that peak turbulent shear stresses of 1000–2000 Pa, which may impact predictive models of hemolysis, were an order of magnitude higher than the peak viscous shear stresses (<100 Pa).39
As CFD is often used in the design and evaluation of circulatory assist devices,1,2,4 the second benchmark model consisted of a centrifugal blood pump with a simple rotor and housing geometry. Pressure head measured across the pump matched well between the PIV and hemolysis tests, whereas some individual CFD predictions varied significantly from the experiments. Although the majority of the pressure head estimates from the CFD submissions were within the experimental bounds, this does not imply that these models are considered validated for the present blood pump. To use CFD to predict hemolysis in blood pumps, validation should be performed at two different levels. The first level of validation should focus on the fluid dynamics including pressure, velocity, and viscous and turbulent stresses. The second level should focus on validating predictions of the biological response (e.g., relative and absolute levels of hemolysis). The amount and rigor of validation required at each level is a function of two factors: 1) how influential the model is in the decision-making process, and 2) the consequence to the patient if the decision made based on the model results is wrong.14 Hence, as the influence of the computational model increases in the regulatory decision-making process, the rigor of validation required to establish its credibility will also increase accordingly. An important, and often overlooked, aspect for medical devices is to ensure that the geometry used in the CFD simulation is the same as the finished, fabricated device and not the nominal “as-designed” device. If the fabricated and design dimensions differ significantly in critical regions of the device (e.g., rotor tip gap of a ventricular assist device, radius of curvature on a sharp corner, surface roughness), this may impact predictions of the local flow fields, shear stresses, blood damage, and the overall performance of the device, regardless of whether the physics are accurately modeled.
This summary article mainly focused on one pump operating condition (6 L/min, 3500 rpm), one plane for the velocity field analysis (i.e., in the upper-blade plane that transected the cutwater and exit tube), and only the steady-state CFD submissions. Reports detailing further results of the CFD and PIV analyses throughout the entire pump, such as the shear stress fields, will follow. Within the body of the pump, which is dominated by rotational flow from the spinning rotor, velocity fields measured in three laboratories using PIV matched well to most of the steady-flow CFD simulations. The largest discrepancies between the CFD and PIV results occurred in the prediction of where the flow separates within the diffuser region. Particle image velocimetry experiments at high flow rates consistently showed a jet angled from the center of the exit volute toward the outer wall of the diffuser, whereas several CFD simulations predicted it on the inner wall or central core of the diffuser. Our subsequent studies will focus on analyzing how different simulation models and input parameters, such as turbulence model, mesh density, and solver type (steady versus unsteady), affect the accuracy of the CFD results in comparison to the interlaboratory PIV and hemolysis results.
The benchmark blood pump model met its design goal of producing more hemolysis than the clinical blood pump at each test condition. This demonstrates that the source of the hemolysis was primarily caused by the blood pump model and not the other components of the flow loops (e.g., backpressure clamp, reservoir, heat exchanger). However, the hemolysis results for the pump model were found to be limited for blood damage validation as the six pump test conditions did not create highly differentiable levels of hemolysis (i.e., generated hemolysis levels for conditions 2–5 were not significantly different from each other). Although the variability in the hemolysis results was high (coefficient of variation was 58–133% for the test conditions), it was comparable to the variability reported for in vitro testing of a clinical blood pump (18–94%).25 The hemolysis level increased significantly at test condition 6 compared with the other test conditions. In preliminary experiments using high-speed video recording of sodium iodide solution at 7 L/min (and 25°C), intermittent cavitation bubbles were visually observed at the cutwater lip. Further studies are needed to determine whether increased blood damage occurred because of infrequent cavitation or from increased flow-induced shear stresses at this test condition.
Notably, only 37% of all CFD submissions provided a hemolysis prediction (11 of 28 submissions for the nozzle, and 8 of 24 submissions for the pump). Possible reasons for the low response rate are that hemolysis solvers are not standard in commercial software and users have to implement the models themselves, or there may be a lack of confidence in the hemolysis models. Hariharan et al.15 recently identified some common user errors in CFD predictions of hemolysis (e.g., incorrect hemolysis units based on experimental data, improper mass-flow weighting). We also observed errors in the benchmark pump study, as three of the eight submitted absolute hemolysis data set predictions did not correspond to their calculated relative hemolysis (RHI) values. This again emphasizes the need for credible verification and validation of hemolysis predictions, both on a relative and absolute scale, to support CFD simulations. To help with the first step in this process, Hariharan et al.15 provided idealized flow-based benchmarks to verify the implementation of commonly cited power law-based hemolysis models in CFD.
A limitation to the current study is that the hemolysis results may only be applicable to the specific blood properties (i.e., porcine blood, 36% hematocrit, 25°C, ACDA anticoagulation, blood age up to 56 hours) and pump model used during testing in one laboratory. Taskin et al.16 reported that power law–based predictions of hemolysis using equation constants from experiments in other laboratories could not accurately reproduce absolute hemolysis levels in blood pump models in their laboratory. However, they did find that an Eulerian scalar transport model of hemolysis estimation could be used for making relative hemolysis comparisons.16 As many factors can affect blood damage test results (e.g., blood species, variability between donors, blood age, anticoagulation, hematocrit, platelet count, temperature, plasma protein and lipid content, glucose level, and pH),40 we advocate interlaboratory blood damage testing over a range of blood preparation conditions to generate robust data for validation on a relative and absolute scale.25 To this end, the FDA is currently working with device industry partners through the Medical Device Innovation Consortium (www.MDIC.org) to develop other benchmark test models and data sets for improving predictive models of blood damage (hemolysis and thrombosis).
In summary, as noted in the FDA-recognized ISO circulatory support device standard,7 the current recommended use of CFD is limited to evaluating relative changes during the device design stage rather than assessing absolute values of predicted quantities. To be further considered as a regulatory-grade tool, CFD simulations must undergo a systematic hierarchical validation of predictions of the flow field, shear stress distribution, and biological response in a device. Commonly used models of blood damage rely on calculations of shear stresses from local velocity gradients. If CFD cannot accurately predict flow patterns in a device, then it cannot provide reliable predictions of the local shear stress field and, consequently, mechanical blood damage.3,24 Our aim was to generate detailed hydrodynamic characterization and hemolysis data for flows through a nozzle and blood pump model to support needed improvements in CFD validation processes for medical devices. Besides the possibility of damage to red blood cells and platelets from high shear stresses, it is also critical to identify recirculation zones in medical devices as they can be the nexus for thrombus formation. Our two benchmark CFD challenges identified significant discrepancies between experimental and computational results that were most prominent in regions where the flow area expanded and flow separation and recirculation occurred. Clearly, more work is needed to identify computational modeling techniques which can better resolve transitional and separating flows, as these characteristics are likely to occur in blood-contacting medical devices. Through the generation of standards,14 FDA Guidance Documents,12 and publicly available experimental benchmark models and data sets, industry, academia, and regulatory bodies can continue to collaboratively develop CFD methodologies to improve the credibility of simulations, which will eventually impact the safety and effectiveness evaluations of medical devices.
Valuable assistance for this project was provided by members of the Technical Planning Committee, including the following: Dr. Sandy Stewart (FDA), Dr. Greg Burgreen (Mississippi State University), Dr. Eric Paterson (Virginia Tech University), and Dr. Matt Myers (FDA). Matthew Giarra (Rochester Institute of Technology) was the principal design engineer for the blood pump model, under the direction of SWD and in collaboration with RAM. Our thanks to FDA personnel Dr. Yao Huang for statistical support, and Dr. Tina Morrison for manuscript review.
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Keywords:Copyright © 2017 by the American Society for Artificial Internal Organs
computational fluid dynamics; validation; medical devices; particle image velocimetry; in vitro hemolysis testing