About

Keefe Manning is a Professor of Biomedical Engineering at Penn State University, affiliated with the College of Engineering. His research focuses on artificial organs and cardiovascular engineering, with particular interest in hemodynamics, hemorheology, cardiovascular prosthetics such as artificial hearts, ventricular assist devices, and mechanical heart valves, as well as blood rheology. Manning's work involves computational modeling and experimental validation to understand blood flow dynamics, device-induced thrombosis, and the development of biomedical devices related to cardiovascular health. He has contributed extensively to the field through research on the performance and fluid dynamics of blood-contacting devices, modeling thrombosis and thromboembolism, and investigating the effects of device placement and blood properties on flow and clot formation. Manning's research aims to improve the design and safety of cardiovascular devices and to advance understanding of blood flow mechanics in medical applications.

Research topics

• Medicine
• Nuclear medicine
• Radiology
• Mechanics
• Internal medicine
• Physics
• Nuclear magnetic resonance
• Cardiology
• Biomedical engineering

Selected publications

• Modeling Red Blood Cell Deformation at Supraphysiological Strain Rates Using a Droplet Framework

  Annals of Biomedical Engineering · 2026-01-29 · 1 citations

  articleOpen accessSenior author

  Abstract Purpose Hemolysis remains a concern in mechanical circulatory support devices (MCSDs). Capturing flow-induced red blood cell (RBC) deformation is important to improve these technologies. Deformation models that are feasible for macroscale MCSD flows have not been calibrated with human RBC deformation data across multiple conditions. The purpose of this study is to modify and test a droplet deformation model that is applicable for MCSD flows for predicting human RBC deformation in silico . Methods In vitro human RBC deformation is studied in microfluidic flows in two suspension viscosities (2.05 and 4.17 cP) at MCSD relevant strain rates (5,000 – 200,000 s -1 in shear flow; 330 – 13,160 s -1 in extensional flow). Modifications are made to the deformation model’s constitutive parameters to represent the observed RBC deformation in silico . Results The calibrated model reproduces the unique RBC deformation behaviors observed in shear and extensional flows across a range of conditions. In silico shear deformation index data have mean absolute error (MAE) ≤ 0.15 compared to in vitro results for both viscosity conditions from 5,000 to 200,000 s -1 . Peak in silico extensional deformation data demonstrate MAE ≤ 0.11 compared to our in vitro results for both viscosity conditions from 670 to 1,300 s -1 , while MAE is higher (up to 0.17) for conditions at 330 s -1 . Conclusion The model adaptations successfully produce accurate RBC deformation results at MCSD relevant strain rates for two flow types and two suspension viscosities. The strengths of the model are in relatively high velocity gradient magnitudes and/or suspension viscosities where RBCs emulate liquid droplets.

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• Computational fluid dynamics assessment of altered hemodynamics in the Circle of Willis during acute ischemic stroke and the impact of cerebral collateral development

  Biomechanics and Modeling in Mechanobiology · 2026-03-27

  articleOpen accessSenior author

  Cerebral collateral assessment has become a common metric for treatment planning in acute ischemic stroke patients due to clinical evidence that well-developed collateral networks are correlated with favorable patient outcomes for reperfusion therapies, such as intravenous thrombolytics and mechanical thrombectomy. However, the mechanisms driving these outcome disparities are not well clarified. In the present study, a computational model is used to help clarify these mechanisms by assessing the Circle of Willis hemodynamics during middle cerebral artery occlusion with different levels of collateral development present. The results showed that middle cerebral artery occlusion causes up to a 30% increase in systemic mean arterial pressure, but the increase is less severe in cases with better collateralization, and cases with well-developed collaterals had up to a 66% lower pressure drop across the clot compared to the cases with poor collateral development. The ipsilateral collateral flow increased up to 20-fold following occlusion, which elevated blood flow and mixing distal to the occlusion. These results indicate that cerebral collaterals serve multiple functions that are important to consider in stroke cases. First, collaterals compensate for part of the lost blood flow to the affected brain region by permitting retrograde flow toward the distal end of the occluded vessel. Second, collaterals reduce the pressure forces on the clot, which can improve the susceptibility to reperfusion therapies. Overall, this study shows that we can leverage our unique computational model to better understand the importance of cerebral collateral circulation during stroke and the influence of collaterals on therapeutic outcomes.

  PublisherDOI

• Characterization of the In Situ Stress State of Blood Clots in Ischemic Stroke: The Effect of Initial Conditions and Arterial Interaction

  International Journal for Numerical Methods in Biomedical Engineering · 2025-10-01 · 2 citations

  articleOpen accessCorresponding

  Ischemic stroke, caused by a blood clot lodging in cerebral vasculature, is a leading cause of death worldwide. The mechanics of vessel occlusion and the influence of residual stress on thrombectomy outcomes remain poorly understood. Most computational studies neglect arterial residual stress and the deformation a clot undergoes as it lodges, both of which elevate system stresses. Here, we introduce a method to simulate the initial state of a clot lodged in an idealized artery with residual stress. In this study, the artery is formulated as two concentric right cylinders with fibers embedded in an isotropic mesh, with a pre-deformation used to incorporate residual stress. A base equilibrium state of an elastic clot is simulated in continuous contact with the arterial wall. The opening angle of the artery, un-lodged-to-lodged dimensional ratios, and stiffness of the clot are varied in parametric sweeps to characterize the traction forces of the clot into the arterial wall. An aspiration pressure is applied to the proximal end of the clot to determine the pressures necessary to begin tensile detachment of the clot. As the artery opening angle increased, removal aspiration pressures increased, while the pressures decreased with increasing artery fiber orientation. The stress-free-to-lodged length ratio of the clot influenced the removal aspiration pressure, with pressures increasing nearly a thousand-fold with increased ratio. By incorporating different factors that contribute to the stress state of the system, this study provides a library of realistic initial conditions for simulating aspiration thrombectomy and validating new surgical techniques.

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• Development, characterization, and curve fitting of rate-dependent models of calcified cerebral embolus analogs for acute ischemic stroke

  Biomechanics and Modeling in Mechanobiology · 2025-08-16

  articleOpen accessSenior author

  Acute ischemic stroke (AIS) is a leading cause of death worldwide. In recent years, several studies have characterized the material properties of clot types that were removed from stroke patients, showing a highly nonlinear, asymmetric behavior in compression and tension. However, little is still known about the clot phenotype underlying complications in endovascular thrombectomy (EVT). In this study, we propose a spectrum of clot surrogates for highly stiff, red blood cell-rich, aged, calcified clots that may underpin the outcomes of AIS procedures, often called 'hyperdense middle cerebral artery signs' by clinicians. This study aims to characterize the high-strain, rate-dependent mechanical properties of a broad range of aged and calcified clot analogs. Blood from healthy donors was used to form aged and calcified clots, which were subjected to rate-dependent uniaxial testing and structural analyses. A method for curve fitting standard linear solids with multiple hyperelastic elements is considered, and a subsequent procedure is outlined for fitting rate-dependent data. High-strain clot analog peak stresses and moduli are on the same order of magnitude as previous studies, with the hypercalcified clots nearly an order of magnitude stiffer than previously recorded. The calcification was shown to be time dependent, as the longer the clots incubated in the calcium solutions, the stiffer they became. SEM images show drastic changes in clot morphology, with mineral nucleation evident around all components of the clot. The curve fitting produced parameters for a host of models that can be used in numerical implementation. The authors note that when curve fitting, energy state of the system should be taken into consideration, in addition to the minimization of the relative error. We demonstrate a wide spectrum of clot properties that are captured well by rate-dependent models for the full dataset, the compressive data, and the tensile data. In this study, we provide a method for creating and characterizing hypercalcified clot analogs as surrogates for the clot phenotype underlying EVT complications. The library of clot properties reported here can be used in numerical simulations, with careful considerations of the curve fitting methods that are employed. These data highlight the need for further investigation into this clot phenotype, which may be related to the subset of AIS patients where clots are unable to be removed.

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• MRI Characterization of Intrathrombus Transport and Flow During Vessel Occlusion

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Intrathrombus transport mechanisms are important to model accurately and to validate thrombolytic behavior but are understudied and not well characterized experimentally. Goal(s): Previous models have largely ignored effective porous diffusivity and used unvalidated porosity-permeability relationships. Our goal is to provide new experimental data to help eliminate or validate these assumptions. Approach: This study aims to use novel MRI applications to quantify intrathrombus convection and diffusion by tracking contrast agent movement through different clot types. Results: Initial results demonstrated we can quantify spatially and temporally varying permeability during dissolution. We also observed decreased diffusivity compared to previously reported values. Impact: Understanding intrathrombus transport mechanisms will provide researchers a better understanding of thrombolytic therapy failure and success. These data can be used to explain why certain clots are clinically more resistant to thrombolytics and to help build better predictive computational models.

  PublisherDOI

• Corrigendum: Modeling flow in an in vitro anatomical cerebrovascular model with experimental validation

  Frontiers in Medical Technology · 2025-01-03

  erratumOpen accessSenior authorCorresponding

  In the published article, there was an error in Figure 3b as published. The simulation was based on an incorrect scale and the values have been updated. The corrected Figure 3b and its caption appear below. In the published article, there was an error in Figure 5 as published. The simulation was conducted using an incorrect scale and these values have been revised. The corrected Figure 5 and its caption appear below. In the published article, there was an error in Table 2 as published. The simulation was conducted using an incorrect scale and these values have been revised. The corrected Table 2 and its caption appear below.In In the published article, there was an error in Table 3 as published. The simulation was conducted using an incorrect scale and these values have been revised. The corrected

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• Computational Modeling of Flow in an in Vitro Cerebrovascular Model Under Pulsatile Conditions with Experimental Validation

  Cardiovascular Engineering and Technology · 2025-12-16

  articleOpen accessSenior authorCorresponding

  PURPOSE: Computational fluid dynamics (CFD) has been widely used to understand various cardiovascular diseases such as acute ischemic stroke (AIS), which occurs when a blood clot lodges in the cerebrovasculature and obstructs blood flow that may lead to brain damage or death. Compared with medical imaging, CFD can predict hemodynamics and clot migration, which are crucial in better understanding the biomechanics of AIS. To rely on computational modeling, however, the simulations need to be validated by comparing with experiments METHODS: In this study, we develop an in vitro experimental model of pulsatile flow in the aorta and cerebrovasculature. The model was filled with a blood analog fluid and pulsatile flow was driven by a piston pump to generate realistic physiological flow conditions. Experimental measurements of the time-varying pressure and flow rate were acquired and are used to validate corresponding CFD simulations RESULTS: CFD predictions of the time-averaged pressure at the outlets are shown to be within 8% of the experimental measurements, while the time-averaged flow rate is within 1%. CONCLUSIONS: This work demonstrates a promising capability for modeling embolus migration and lodging in the brain. Future work will validate simulations of clot migration that may be used to better understand AIS biomechanics and treatment options.

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• A hyper-viscoelastic uniaxial characterization of collagenous embolus analogs in acute ischemic stroke

  Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · 2024-08-24 · 4 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Abstract 4140488: Late Gadolinium Enhancement CMR Tissue Characterization for Central Venous Catheter Associated Right Atrial Thrombus – Structural Risk Factors and Stratification of Embolic Outcomes among Systemic Cancer Patients

  Circulation · 2024-11-12

  article

  Background: Central venous catheters (CVC) are common in cancer pts but provide a nidus for right atrial thrombus (RA-Th). CMR can identify presence and risk factors for RA-Th. Objectives: To evaluate predisposing factors and embolic risk conferred by RA-Th. Methods: The population comprised adult (≥18yo) cancer pts with CVC who underwent CMR at two sites; RA-Th was defined by avascularity on LGE-CMR. Registry data included clinical and CVC indices and chart review for pulmonary embolism (PE) 1 month pre- or 6 months post-CMR. Results: 211 pts with CVC (52±17yo; 45% M) were studied, inclusive of RA-Th and controls matched for cancer etiology/stage (heme 28%| GI 27%| sarcoma 22%). CVC type varied (Mediport 81% |PICC 9%| pheresis 6%| HD 4%), as did time between RA-Th and catheter insertion (6.5[2.4-15.8] mo). Pts with and w/o RA-Th were of similar age, sex, CVC type/duration, and cardiac function on CMR (p=NS). CVC depth was greater in pts with RA-Th (2.8±1.6cm vs. 1.5±1.6cm, p<0.001). Prevalence of RA-Th increased in proportion to CVC depth (<1|1-3|>3cm from SVC-RA: 31%|57%|75%; p<0.001 without influencing RA-Th size (p=NS). Anticoagulation (LMWH 42%| NOAC 25%| warfarin 3.4%| combination 26%) was more common in pts with RA-Th (99% vs. 43%; p<0.001). Despite this, RA-Th was strongly associated with embolic risk, as shown by >5-fold higher incidence of PE vs. controls (16% vs 2.5%, p=0.002; OR=7.08 [CI 1.58–31.78], p=0.01; Table 1 ). In pts with RA-Th and PE (n=17), majority of PE (59%) occurred within 1mo of CMR, and the remaining occurred within 1-6mo after CMR ( Fig 1 ). Among pts with RA-Th, the likelihood of PE increased with high lesion mobility (27% vs 10%, p=0.02; OR=3.38 [CI 1.13–10.1], p=0.03). Conclusions: Increased catheter depth increases risk for RA-Th implicating mechanical factors as a key thrombogenic driver. Despite anticoagulation, patients with RA-Th are at markedly higher risk for embolic events, particularly within the first month of detection on CMR.

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• Influence of Hematocrit Level and Integrin αIIbβIII Function on vWF-Mediated Platelet Adhesion and Shear-Induced Platelet Aggregation in a Sudden Expansion

  Cellular and Molecular Bioengineering · 2024-02-01 · 8 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

Recent grants

• A Structured Approach to the Design of Minimally Traumatic Blood Pumps

  NIH · $2.6M · 2018–2024

• Developing a Computational Model to Predict Clot Transport

  NSF · $548k · 2020–2025

Frequent coauthors

• Steven Deutsch

  105 shared

• Brent A. Craven

  Pennsylvania State University

  51 shared

• Arnold A. Fontaine

  Pennsylvania State University

  44 shared

• Bryan C. Good

  University of Tennessee at Knoxville

  28 shared

• Luke H. Herbertson

  United States Food and Drug Administration

  24 shared

• Jason Weiss

  Oregon State University

  22 shared

• John M. Tarbell

  City College of New York

  22 shared

• Kenneth I. Aycock

  United States Food and Drug Administration

  20 shared

Labs

• Keefe Manning LaboratoryPI