Keefe B. Manning

Bio: Keefe B. Manning is an academic researcher from Pennsylvania State University. The author has contributed to research in topics: Pulsatile flow & Particle image velocimetry. The author has an hindex of 22, co-authored 108 publications receiving 1888 citations. Previous affiliations of Keefe B. Manning include Virginia Commonwealth University & Penn State Milton S. Hershey Medical Center.

Assessment of CFD Performance in Simulations of an Idealized Medical Device: Results of FDA’s First Computational Interlaboratory Study

Abstract: While computational fluid dynamics (CFD) is commonly used for medical device development, its usefulness for demonstrating device safety has not been proven. Reliable standardized methods for this specialized need are lacking and are inhibiting the use of computational methods in the regulatory review of medical devices. To meet this need, participants from academia, industry, and the U.S. Food and Drug Administration recently completed a computational interlaboratory study to determine the suitability and methodology for simulating fluid flow in an idealized medical device. A technical working committee designed the study, defined the model geometry and flow conditions, and identified comparison metrics. The model geometry was a 0.012 m diameter cylindrical nozzle with a conical collector and sudden expansion on either side of a 0.04 m long, 0.004 m diameter throat, which is able to cause hemolysis under certain flow conditions. Open invitations to participate in the study were extended through professional societies and organizations. Twenty-eight groups from around the world submitted simulation results for five flow rates, spanning laminar, transitional, and turbulent flows. Concurrently, three laboratories generated experimental validation data on geometrically similar physical models using particle image velocimetry. The simulations showed considerable variation from each other and from experiment. One main source of error involved turbulence model underestimations of the centerline velocities in the inlet and throat regions, because the flow was laminar in these regions. Turbulence models were also unable to accurately predict velocities and shear stresses in the recirculation zones downstream of the sudden expansion. The wide variety in results suggest that CFD studies used to assess safety in medical device submissions to the FDA require careful experimental validation. Better transitional models are needed, as many medical devices operate in the transitional regime. It is imperative that the community undertake and publish quality validation cases of biofluid dynamics and blood damage that include complications such as pulsatility, secondary flows, and short and/or curved inlets and outlets. The results of this interlaboratory study will be available in a benchmark database to help develop improved modeling techniques, and consensus standards and guidelines for using CFD in the evaluation of medical devices.

Multilaboratory Particle Image Velocimetry Analysis of the FDA Benchmark Nozzle Model to Support Validation of Computational Fluid Dynamics Simulations

Abstract: This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re throat ) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re throat = 500) and turbulent flow conditions (Re throat ≥ 3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re throat = 2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models.

Experimental fluid mechanics of pulsatile artificial blood pumps

Abstract: The fluid mechanics of artificial blood pumps has been studied since the early 1970s in an attempt to understand and mitigate hemolysis and thrombus formation by the device. Pulsatile pumps are characterized by inlet jets that set up a rotational “washing” pattern during filling. Strong regurgitant jets through the closed artificial heart valves have Reynolds stresses on the order of 10,000 dynes/cm 2 and are the most likely cause of red blood cell damage and platelet activation. Although the flow in the pump chamber appears benign, low wall shear stresses throughout the pump cycle can lead to thrombus formation at the wall of the smaller pumps (10–50 cc). The local fluid mechanics is critical. There is a need to rapidly measure or calculate the wall shear stress throughout the device so that the results may be easily incorporated into the design process.

FDA Benchmark Medical Device Flow Models for CFD Validation.

Abstract: 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.

Fast parallel algorithms for short-range molecular dynamics

Abstract: Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Theory of cross-correlation analysis of PIV images : Image analysis as measuring technique in flows

Abstract: To improve the performance of particle image velocimetry in measuring instantaneous velocity fields, direct cross-correlation of image fields can be used in place of auto-correlation methods of interrogation of double- or multiple-exposure recordings. With improved speed of photographic recording and increased resolution of video array detectors, cross-correlation methods of interrogation of successive single-exposure frames can be used to measure the separation of pairs of particle images between successive frames. By knowing the extent of image shifting used in a multiple-exposure and by a priori knowledge of the mean flow-field, the cross-correlation of different sized interrogation spots with known separation can be optimized in terms of spatial resolution, detection rate, accuracy and reliability.

New insights into large eddy simulation

Abstract: Fluid dynamic turbulence is one of the most challenging computational physics problems because of the extremely wide range of time and space scales involved, the strong nonlinearity of the governing equations, and the many practical and important applications. While most linear fluid instabilities are well understood, the nonlinear interactions among them makes even the relatively simple limit of homogeneous isotropic turbulence difficult to treat physically, mathematically, and computationally. Turbulence is modeled computationally by a two-stage bootstrap process. The first stage, direct numerical simulation, attempts to resolve the relevant physical time and space scales but its application is limited to diffusive flows with a relatively small Reynolds number (Re). Using direct numerical simulation to provide a database, in turn, allows calibration of phenomenological turbulence models for engineering applications. Large eddy simulation incorporates a form of turbulence modeling applicable when the large-scale flows of interest are intrinsically time dependent, thus throwing common statistical models into question. A promising approach to large eddy simulation involves the use of high-resolution monotone computational fluid dynamics algorithms such as flux-corrected transport or the piecewise parabolic method which have intrinsic subgrid turbulence models coupled naturally to the resolved scales in the computed flow. The physical considerations underlying and evidence supporting this monotone integrated large eddy simulation approach are discussed.