Luke H. Herbertson

Fda Benchmark Medical Device Flow Models for Cfd Validation.

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal’s Web site (www.asaiojournal.com) to listen.

Wavelet Transforms in the Analysis of Mechanical Heart Valve Cavitation

Cavitation is known to cause blood element damage and may introduce gaseous emboli into the cerebral circulation, increasing the patients risk of stroke. Discovering methods to reduce the intensity of cavitation induced by mechanical heart valves (MHVs) has long been an area of interest. A novel approach for analyzing MHV cavitation is presented. A wavelet denoising method is explored because currently used analytical techniques fail to suitably unmask the cavitation signal from other valve closing sounds and noise detected with a hydrophone. Wavelet functions are used to denoise the cavitation signal during MHV closure and rebound. The wavelet technique is applied to the signal produced by closure of a 29-mm Medtronic-Hall MHV in degassed water with a gas content of 5 ppm. Valve closing dynamics are investigated under loading conditions of 500, 2500, and 4500 mm Hg/s. The results display a marked improvement in the quantity and quality of information that can be extracted from acoustic cavitation signals using the wavelet technique compared to conventional analytical techniques. Time and frequency data indicate the likelihood and characteristics of cavitation formation under specified conditions. Using this wavelet technique we observe an improved signal-to-noise ratio, an enhanced time-dependent aspect, and the potential to minimize valve closing sounds, which disguise individual cavitation events. The overall goal of this work is to eventually link specific valves with characteristic waveforms or distinct types of cavitation, thus promoting improved valve designs.

Multilaboratory Study of Flow-Induced Hemolysis Using the FDA Benchmark Nozzle Model

Multilaboratory in vitro blood damage testing was performed on a simple nozzle model to determine how different flow parameters and blood properties affect device-induced hemolysis and to generate data for comparison with computational fluid dynamics-based predictions of blood damage as part of an FDA initiative for assessing medical device safety. Three independent laboratories evaluated hemolysis as a function of nozzle entrance geometry, flow rate, and blood properties. Bovine blood anticoagulated with acid citrate dextrose solution (2-80 h post-draw) was recirculated through nozzle-containing and paired nozzle-free control loops for 2 h. Controlled parameters included hematocrit (36 ± 1.5%), temperature (25 °C), blood volume, flow rate, and pressure. Three nozzle test conditions were evaluated (n = 26-36 trials each): (i) sudden contraction at the entrance with a blood flow rate of 5 L/min, (ii) gradual cone at the entrance with a 6-L/min blood flow rate, and (iii) sudden-contraction inlet at 6 L/min. The blood damage caused only by the nozzle model was calculated by subtracting the hemolysis generated by the paired control loop test. Despite high intralaboratory variability, significant differences among the three test conditions were observed, with the sharp nozzle entrance causing the most hemolysis. Modified index of hemolysis (MIHnozzle ) values were 0.292 ± 0.249, 0.021 ± 0.128, and 1.239 ± 0.667 for conditions i-iii, respectively. Porcine blood generated hemolysis results similar to those obtained with bovine blood. Although the interlaboratory hemolysis results are only applicable for the specific blood parameters and nozzle model used here, these empirical data may help to advance computational fluid dynamics models for predicting blood damage.

Limitations of using synthetic blood clots for measuring in vitro clot capture efficiency of inferior vena cava filters

The purpose of this study was first to evaluate the clot capture efficiency and capture location of six currently-marketed vena cava filters in a physiological venous flow loop, using synthetic polyacrylamide hydrogel clots, which were intended to simulate actual blood clots. After observing a measured anomaly for one of the test filters, we redirected the focus of the study to identify the cause of poor clot capture performance for large synthetic hydrogel clots. We hypothesized that the uncharacteristic low clot capture efficiency observed when testing the outlying filter can be attributed to the inadvertent use of dense, stiff synthetic hydrogel clots, and not as a result of the filter design or filter orientation. To study this issue, sheep blood clots and polyacrylamide (PA) synthetic clots were injected into a mock venous flow loop containing a clinical inferior vena cava (IVC) filter, and their captures were observed. Testing was performed with clots of various diameters (3.2, 4.8, and 6.4 mm), length-to-diameter ratios (1:1, 3:1, 10:1), and stiffness. By adjusting the chemical formulation, PA clots were fabricated to be soft, moderately stiff, or stiff with elastic moduli of 805 ± 2, 1696 ± 10 and 3295 ± 37 Pa, respectively. In comparison, the elastic moduli for freshly prepared sheep blood clots were 1690 ± 360 Pa. The outlying filter had a design that was characterized by peripheral gaps (up to 14 mm) between its wire struts. While a low clot capture rate was observed using large, stiff synthetic clots, the filter effectively captured similarly sized sheep blood clots and soft PA clots. Because the stiffer synthetic clots remained straight when approaching the filter in the IVC model flow loop, they were more likely to pass between the peripheral filter struts, while the softer, physiological clots tended to fold and were captured by the filter. These experiments demonstrated that if synthetic clots are used as a surrogate for animal or human blood clots for in vitro evaluation of vena cava filters, the material properties (eg, elastic modulus) and dynamic behavior of the surrogate should first be assessed to ensure that they accurately mimic an actual blood clot within the body.

Near Valve Flows and Potential Blood Damage During Closure of a Bileaflet Mechanical Heart Valve

Blood damage and thrombosis are major complications that are commonly seen in patients with implanted mechanical heart valves. For this in vitro study, we isolated the closing phase of a bileaflet mechanical heart valve to study near valve fluid velocities and stresses. By manipulating the valve housing, we gained optical access to a previously inaccessible region of the flow. Laser Doppler velocimetry and particle image velocimetry were used to characterize the flow regime and help to identify the key design characteristics responsible for high shear and rotational flow. Impact of the closing mechanical leaflet with its rigid housing produced the highest fluid stresses observed during the cardiac cycle. Mean velocities as high as 2.4 m/s were observed at the initial valve impact. The velocities measured at the leaflet tip resulted in sustained shear rates in the range of 1500-3500 s(-1), with peak values on the order of 11,000-23,000 s(-1). Using velocity maps, we identified regurgitation zones near the valve tip and through the central orifice of the valve. Entrained flow from the transvalvular jets and flow shed off the leaflet tip during closure combined to generate a dominant vortex posterior to both leaflets after each valve closing cycle. The strength of the peripheral vortex peaked within 2 ms of the initial impact of the leaflet with the housing and rapidly dissipated thereafter, whereas the vortex near the central orifice continued to grow during the rebound phase of the valve. Rebound of the leaflets played a secondary role in sustaining closure-induced vortices.

A dialyzer-based flow system for validating dynamic contrast enhanced MR image acquisition

Dynamic contrast enhanced magnetic resonance imaging (MRI) has proven to be quite sensitive for the characterization of masses and early response to therapy. However, it is fraught with a number of procedural challenges as well as a lack of standardization. In this article, we describe the use of a simple dialyzer‐based flow system to evaluate reproducibility of dynamic contrast enhanced MRI under active flow conditions.

A Reusable, Compliant, Small Volume Blood Reservoir for In Vitro Hemolysis Testing.

Bench-top in vitro hemolysis testing is a fundamental tool during the design and regulatory safety evaluation of blood-contacting medical devices. While multiple published experimental protocols exist, descriptions of the test loop reservoir remain ambiguous. A critical fixture within the circuit, there is no readily available blood reservoir that ensures thorough mixing and complete air evacuation: two major factors which can affect results. As part of the Food and Drug Administration (FDA) Critical Path Initiative, we developed a three-piece reservoir consisting of a 3D-printed base, a plastic clamp set, and a medical-grade blood bag. This simple, reusable, and cost-effective design was used successfully in the hemolysis assessment of FDA benchmark nozzles and prototype rotary blood pumps, and may be useful as an integral component to any in vitro blood circulation loop.

Correlating Leaflet Design and Closing Dynamics With Turbulent Flows Near Bileaflet Mechanical Heart Valves

Significant advances have been made in the field of heart valve replacement, especially in terms of anticoagulation therapy and valve design. Mechanical heart valves have been successfully implanted for decades to replace irreparable diseased or failing native valves. However, heart valve patients remain more susceptible to hemolysis and thrombosis [1]. In this experimental study, we focus on the closing dynamics of bileaflet mechanical heart valves to better understand the roles that valve design and environmental conditions have on the local fluid mechanics.Copyright

Fluid Mechanical Analysis at Closure of the On-X Mechanical Heart Valve

Three-dimensional laser Doppler velocimetry (LDV) was used to characterize the flow created by the On-X bileaflet mechanical heart valve (MHV) manufactured by Medical Carbon Research Institute (MCRI), Inc. (Austin, TX). The valve was mounted into a pneumatically driven single-shot chamber in the mitral position such that only the closure dynamics were simulated. Measurements taken 2 mm proximal to the valve housing showed a peak velocity of 1.8 m/s and maximum Reynolds Shear Stresses (RSS) of 17,500 dynes/cm2, which were found along the centerline of the valve in the hinge region 2 ms after valve closure. The large velocity and RSS gradients denote the presence of complex flow structures. These results provide an initial basis for understanding the impact of valve geometry on hemolysis and thrombosis associated with the On-X MHV.Copyright

Development of a Wavelet Analytical Tool for Isolating and Evaluating Cavitation-Induced Hemolysis Generated During Mechanical Heart Valve Closure

Cavitation formed during the closure of mechanical heart valves (MHVs) can harm nearby blood cells and valve surfaces. In this study we focus on an approach to accurately measure cavitation energy in order to compare the effectiveness of replacement valves. Cavitation energy is difficult to measure acoustically because it is masked by other pressure fluctuations in the body or system. To improve upon currently used analytical techniques, a wavelet isolation technique was developed to quantify cavitation energy. With this method, acoustic signals captured by a hydrophone are decomposed, denoised, and then reconstructed. Wavelet analysis should prove to be particularly valuable in vivo, where visual evidence of cavitation cannot be obtained.Copyright