Alison Marsden is an associate professor and Wall Center scholar in the departments of Pediatrics, Bioengineering, and, by courtesy, Mechanical Engineering at Stanford University. From 2007-2015 she was a faculty member in the Mechanical and Aerospace Engineering Department at the University of California San Diego. She graduated with a bachelor's degree in Mechanical Engineering from Princeton University in 1998, and a PhD in Mechanical Engineering from Stanford in 2005 working with Prof. Parviz Moin. She was a postdoctoral fellow at Stanford University in Bioengineering and Pediatric Cardiology from 2005-07 working with Charles Taylor and Jeffrey Feinstein. She was the recipient of a Burroughs Wellcome Fund Career Award at the Scientific Interface in 2007, an NSF CAREER award in 2011, and is a fellow of the American Institute of Medical and Biological Engineers and the Society for Industrial and Applied Mathematics. She received the UCSD graduate student association faculty mentor award in 2014 and MAE department teaching award at UCSD in 2015. She has published over 90 peer reviewed journal papers, and has received funding from the NSF, NIH, and several private foundations. She is currently on the editorial boards of several leading journals in biomechanics. Her work focuses on the development of numerical methods for cardiovascular blood flow simulation, medical device design, application of optimization to large-scale fluid mechanics simulations, and application of engineering tools to impact patient care in cardiovascular surgery and congenital heart disease.

Academic Appointments

Honors & Awards

  • Fellow, American Institute of Medical and Biological Engineers (2018)
  • Fellow, Society for Industrial and Applied Mathematics (2018)
  • Vera Moulton Wall Center, Faculty Scholar (2016)
  • Teacher of the year, MAE department, UCSD (2015)
  • Graduate student association faculty mentor award, University of California San Diego (2014)
  • CAREER Award, National Science Foundation (2012)
  • Career Award at the Scientific Interface, Burroughs Wellcome Fund (2007)

Boards, Advisory Committees, Professional Organizations

  • Advisory Board, Burroughs Wellcome Fund CASI Program (2016 - Present)
  • Associate Editor, Journal of Biomechanical Engineering (2014 - Present)
  • Section Editor, Current Opinion in Biomedical Engineering (2016 - Present)
  • Associate Editor, PLOS Computational Biology (2016 - Present)

Professional Education

  • BSE, Princeton University, Mechanical Engineering (1998)
  • MSE, Stanford University, Mechanical Engineering (2000)
  • PhD, Stanford University, Mechanical Engineering (2005)

Research & Scholarship

Current Research and Scholarly Interests

The Cardiovascular Biomechanics Computation Lab at Stanford develops novel computational methods for the study of cardiovascular disease progression, surgical methods, and medical devices. We have a particular interest in pediatric cardiology, and use virtual surgery to design novel surgical concepts for children born with heart defects.


2018-19 Courses

Stanford Advisees

Graduate and Fellowship Programs


All Publications

  • Uncertainty quantification of simulated biomechanical stimuli in coronary artery bypass grafts COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Tran, J. S., Schiavazzi, D. E., Kahn, A. M., Marsden, A. L. 2019; 345: 402–28
  • Hemodynamic variables in aneurysms are associated with thrombotic risk in children with Kawasaki disease. International journal of cardiology Grande Gutierrez, N., Mathew, M., McCrindle, B. W., Tran, J. S., Kahn, A. M., Burns, J. C., Marsden, A. L. 2019


    BACKGROUND: Thrombosis is a major adverse outcome associated with coronary artery aneurysms (CAAs) resulting from Kawasaki disease (KD). Clinical guidelines recommend initiation of anticoagulation therapy with maximum CAA diameter (Dmax) ≥8 mm or Z-score ≥ 10. Here, we investigate the role of aneurysm hemodynamics as a superior method for thrombotic risk stratification in KD patients.METHODS AND RESULTS: We retrospectively studied ten KD patients with CAAs, including five patients who developed thrombosis. We constructed patient-specific anatomic models from cardiac magnetic resonance images and performed computational hemodynamic simulations using SimVascular. Our simulations incorporated pulsatile flow, deformable arterial walls and boundary conditions automatically tuned to match patient-specific arterial pressure and cardiac output. From simulation results, we derived local hemodynamic variables including time-averaged wall shear stress (TAWSS), low wall shear stress exposure, and oscillatory shear index (OSI). Local TAWSS was significantly lower in CAAs that developed thrombosis (1.2 ± 0.94 vs. 7.28 ± 9.77 dynes/cm2, p = 0.006) and the fraction of CAA surface area exposed to low wall shear stress was larger (0.69 ± 0.17 vs. 0.25 ± 0.26%, p = 0.005). Similarly, longer residence times were obtained in branches where thrombosis was confirmed (9.07 ± 6.26 vs. 2.05 ± 2.91 cycles, p = 0.004). No significant differences were found for OSI or anatomical measurements such us Dmax and Z-score. Assessment of thrombotic risk according to hemodynamic variables had higher sensitivity and specificity compared to standard clinical metrics (Dmax, Z-score).CONCLUSIONS: Hemodynamic variables can be obtained non-invasively via simulation and may provide improved thrombotic risk stratification compared to current diameter-based metrics, facilitating long-term clinical management of KD patients with persistent CAAs.

    View details for DOI 10.1016/j.ijcard.2019.01.092

    View details for PubMedID 30728104

  • Evolution of hemodynamic forces in the pulmonary tree with progressively worsening pulmonary arterial hypertension in pediatric patients. Biomechanics and modeling in mechanobiology Yang, W., Dong, M., Rabinovitch, M., Chan, F. P., Marsden, A. L., Feinstein, J. A. 2019


    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling resulting in right ventricular (RV) dysfunction and ultimately RV failure. Mechanical stimuli acting on the vessel walls of the full pulmonary tree have not previously been comprehensively characterized. The goal of this study is to characterize wall shear stress (WSS) and strain in pediatric PAH patients at different stages of disease severity using computational patient-specific modeling. Computed tomography, magnetic resonance imaging and right heart catheterization data were collected and assimilated into pulmonary artery (PA) models for patients with and without PAH. Patients were grouped in three disease severity groups (control, moderate and severe) based on clinical evaluations. A finite element solver was employed to quantify hemodynamics and wall strains. To estimate WSS in the distal small PAs with diameters ranging from 50 to 500[Formula: see text], a morphometric tree model was created, with inputs coming from outlets of the 3D model. WSS in the proximal PAs decreased with disease severity (control 20.5 vs. moderate 15.8 vs. severe 6.3[Formula: see text], [Formula: see text]). Oscillatory shear index increased in the main pulmonary artery (MPA) with disease severity (0.13 vs. 0.13 vs. 0.2, [Formula: see text]). Wall strains measured by the first invariant of Green strain tensor decreased with disease severity (0.16 vs. 0.12 vs. 0.11, [Formula: see text]). Mean WSS for the distal PAs between 100 and 500[Formula: see text] significantly increased with disease severity (20 vs. 52 vs. 116 [Formula: see text], [Formula: see text]). In conclusion, 3D flow simulations showed that WSS is significantly decreased in the MPA with disease while the mathematical morphometric model suggested increased WSS in the distal small vessels. Computational models can reveal mechanical stimuli acting on vessel walls that may inform patient risk stratification and flow shear experiments.

    View details for PubMedID 30635853

  • Simulating Developmental Cardiac Morphology in Virtual Reality Using a Deformable Image Registration Approach ANNALS OF BIOMEDICAL ENGINEERING Abiri, A., Ding, Y., Abiri, P., Packard, R., Vedula, V., Marsden, A., Kuo, C., Hsiai, T. K. 2018; 46 (12): 2177–88


    While virtual reality (VR) has potential in enhancing cardiovascular diagnosis and treatment, prerequisite labor-intensive image segmentation remains an obstacle for seamlessly simulating 4-dimensional (4-D, 3-D + time) imaging data in an immersive, physiological VR environment. We applied deformable image registration (DIR) in conjunction with 3-D reconstruction and VR implementation to recapitulate developmental cardiac contractile function from light-sheet fluorescence microscopy (LSFM). This method addressed inconsistencies that would arise from independent segmentations of time-dependent data, thereby enabling the creation of a VR environment that fluently simulates cardiac morphological changes. By analyzing myocardial deformation at high spatiotemporal resolution, we interfaced quantitative computations with 4-D VR. We demonstrated that our LSFM-captured images, followed by DIR, yielded average dice similarity coefficients of 0.92 ± 0.05 (n = 510) and 0.93 ± 0.06 (n = 240) when compared to ground truth images obtained from Otsu thresholding and manual segmentation, respectively. The resulting VR environment simulates a wide-angle zoomed-in view of motion in live embryonic zebrafish hearts, in which the cardiac chambers are undergoing structural deformation throughout the cardiac cycle. Thus, this technique allows for an interactive micro-scale VR visualization of developmental cardiac morphology to enable high resolution simulation for both basic and clinical science.

    View details for DOI 10.1007/s10439-018-02113-z

    View details for Web of Science ID 000451997300019

    View details for PubMedID 30112710

    View details for PubMedCentralID PMC6249076

  • A unified continuum and variational multiscale formulation for fluids, solids, and fluid-structure interaction COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Liu, J., Marsden, A. L. 2018; 337: 549–97
  • Spatial and temporal variations in hemodynamic forces initiate cardiac trabeculation JCI INSIGHT Lee, J., Vedula, V., Baek, K., Chen, J., Hsu, J. J., Ding, Y., Chang, C., Kang, H., Small, A., Fei, P., Chuong, C., Li, R., Demer, L., Packard, R., Marsden, A. L., Hsiai, T. K. 2018; 3 (13)


    Hemodynamic shear force has been implicated as modulating Notch signaling-mediated cardiac trabeculation. Whether the spatiotemporal variations in wall shear stress (WSS) coordinate the initiation of trabeculation to influence ventricular contractile function remains unknown. Using light-sheet fluorescent microscopy, we reconstructed the 4D moving domain and applied computational fluid dynamics to quantify 4D WSS along the trabecular ridges and in the groves. In WT zebrafish, pulsatile shear stress developed along the trabecular ridges, with prominent endocardial Notch activity at 3 days after fertilization (dpf), and oscillatory shear stress developed in the trabecular grooves, with epicardial Notch activity at 4 dpf. Genetic manipulations were performed to reduce hematopoiesis and inhibit atrial contraction to lower WSS in synchrony with attenuation of oscillatory shear index (OSI) during ventricular development. γ-Secretase inhibitor of Notch intracellular domain (NICD) abrogated endocardial and epicardial Notch activity. Rescue with NICD mRNA restored Notch activity sequentially from the endocardium to trabecular grooves, which was corroborated by observed Notch-mediated cardiomyocyte proliferations on WT zebrafish trabeculae. We also demonstrated in vitro that a high OSI value correlated with upregulated endothelial Notch-related mRNA expression. In silico computation of energy dissipation further supports the role of trabeculation to preserve ventricular structure and contractile function. Thus, spatiotemporal variations in WSS coordinate trabecular organization for ventricular contractile function.

    View details for PubMedID 29997298

  • Benchmark problems for numerical treatment of backflow at open boundaries INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Bertoglio, C., Caiazzo, A., Bazilevs, Y., Braack, M., Esmaily, M., Gravemeier, V., Marsden, A. L., Pironneau, O., Vignon-Clementel, I. E., Wall, W. A. 2018; 34 (2)

    View details for DOI 10.1002/cnm.2918

    View details for Web of Science ID 000424359400006

  • Optimization of the Assisted Bidirectional Glenn Procedure for First Stage Single Ventricle Repair Optimization of the Assisted Bidirectional Glenn Procedure for First Stage Single Ventricle Repair Verma, A., Esmaily, M., Shang, J., Figliola, R., Feinstein, J., Hsia, T., Marsden, A. 2018; 9 (2): 157-170


    First-stage single-ventricle palliation is challenging to manage, and significant interstage morbidity and mortality remain. Prior computational and in vitro studies of the assisted bidirectional Glenn (ABG), a novel first-stage procedure that has shown potential for early conversion to a more stable augmented Glenn physiology, demonstrated increased pulmonary flow and oxygen delivery while decreasing cardiac work, as compared to conventional stage-1 alternatives. This study aims to identify optimal shunt designs for the ABG to improve pulmonary flow while maintaining or decreasing superior vena caval (SVC) pressure.A representative three-dimensional model of a neonatal bidirectional Glenn (BDG) was created, with a shunt connecting the innominate artery to the SVC. The shunt design was studied as a six-parameter constrained shape optimization problem. We simulated hemodynamics for each candidate designs using a multiscale finite element flow solver and compared performance against designs with taper-less shunts, the standalone BDG, and a simplified control volume model. Three values of pulmonary vascular resistance (PVR) of 2.3, 4.3, and 7.1 WUm2 were studied.Increases in pulmonary flow were generally accompanied by increases in SVC pressure, except at low PVR (2.3 WUm2), where the optimal shunt geometry achieved a 13% increase in pulmonary flow without incurring any increase in SVC pressure. Shunt outlet area was the most influential design parameter, while others had minimal effect.Assisted bidirectional Glenn performance is sensitive to PVR and shunt outlet diameter. An increase in pulmonary flow without a corresponding increase in SVC pressure is possible only when PVR is low.

    View details for DOI 10.1177/2150135117745026

  • Right Ventricular Stroke Work Correlates with Outcomes in Pediatric Pulmonary Arterial Hypertension. Pulmonary circulation Yang, W., Marsden, A. L., Ogawa, M. T., Sakarovitch, C., Hall, K. K., Rabinovitch, M., Feinstein, J. A. 2018: 2045894018780534

    View details for PubMedID 29767574

  • A re-engineered interface and workflow for the open source SimVascular cardiovascular modeling package A re-engineered interface and workflow for the open source SimVascular cardiovascular modeling package Lan, H., Updegrove, A., Wilson, N., Maher, G., Shadden, S., Marsden, A. 2018; 140 (2): 024501-024501-11


    Patient-specific simulation plays an important role in cardiovascular disease research, diagnosis, surgical planning and medical device design, as well as education in cardiovascular biomechanics. simvascular is an open-source software package encompassing an entire cardiovascular modeling and simulation pipeline from image segmentation, three-dimensional (3D) solid modeling, and mesh generation, to patient-specific simulation and analysis. SimVascular is widely used for cardiovascular basic science and clinical research as well as education, following increased adoption by users and development of a GATEWAY web portal to facilitate educational access. Initial efforts of the project focused on replacing commercial packages with open-source alternatives and adding increased functionality for multiscale modeling, fluid-structure interaction (FSI), and solid modeling operations. In this paper, we introduce a major SimVascular (SV) release that includes a new graphical user interface (GUI) designed to improve user experience. Additional improvements include enhanced data/project management, interactive tools to facilitate user interaction, new boundary condition (BC) functionality, plug-in mechanism to increase modularity, a new 3D segmentation tool, and new computer-aided design (CAD)-based solid modeling capabilities. Here, we focus on major changes to the software platform and outline features added in this new release. We also briefly describe our recent experiences using SimVascular in the classroom for bioengineering education.

    View details for DOI 10.1115/1.4038751

    View details for PubMedCentralID PMC5816252

  • Computational blood flow simulations in Kawasaki disease patients: Insight into coronary artery aneurysm hemodynamics. Global cardiology science & practice Grande Gutierrez, N., Kahn, A., Burns, J. C., Marsden, A. L. 2017; 2017 (3): e201729

    View details for DOI 10.21542/gcsp.2017.29

    View details for PubMedID 29564350

  • Gradual loading ameliorates maladaptation in computational simulations of vein graft growth and remodelling. Journal of the Royal Society, Interface Ramachandra, A. B., Humphrey, J. D., Marsden, A. L. 2017; 14 (130)


    Vein graft failure is a prevalent problem in vascular surgeries, including bypass grafting and arteriovenous fistula procedures in which veins are subjected to severe changes in pressure and flow. Animal and clinical studies provide significant insight, but understanding the complex underlying coupled mechanisms can be advanced using computational models. Towards this end, we propose a new model of venous growth and remodelling (G&R) based on a constrained mixture theory. First, we identify constitutive relations and parameters that enable venous adaptations to moderate perturbations in haemodynamics. We then fix these relations and parameters, and subject the vein to a range of combined loads (pressure and flow), from moderate to severe, and identify plausible mechanisms of adaptation versus maladaptation. We also explore the beneficial effects of gradual increases in load on adaptation. A gradual change in flow over 3 days plus an initial step change in pressure results in fewer maladaptations compared with step changes in both flow and pressure, or even a gradual change in pressure and flow over 3 days. A gradual change in flow and pressure over 8 days also enabled a successful venous adaptation for loads as severe as the arterial loads. Optimization is used to accelerate parameter estimation and the proposed framework is general enough to provide a good starting point for parameter estimations in G&R simulations.

    View details for DOI 10.1098/rsif.2016.0995

    View details for PubMedID 28566510

  • Optimizing fluid-structure interaction systems with immersogeometric analysis and surrogate modeling: Application to a hydraulic arresting gear COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Wu, M. C., Kamensky, D., Wang, C., Herrema, A. J., Xu, F., Pigazzini, M. S., Verma, A., Marsden, A. L., Bazilevs, Y., Hsu, M. 2017; 316: 668-693
  • Patient-specific parameter estimation in single-ventricle lumped circulation models under uncertainty. International journal for numerical methods in biomedical engineering Schiavazzi, D. E., Baretta, A., Pennati, G., Hsia, T., Marsden, A. L. 2017; 33 (3)


    Computational models of cardiovascular physiology can inform clinical decision-making, providing a physically consistent framework to assess vascular pressures and flow distributions, and aiding in treatment planning. In particular, lumped parameter network (LPN) models that make an analogy to electrical circuits offer a fast and surprisingly realistic method to reproduce the circulatory physiology. The complexity of LPN models can vary significantly to account, for example, for cardiac and valve function, respiration, autoregulation, and time-dependent hemodynamics. More complex models provide insight into detailed physiological mechanisms, but their utility is maximized if one can quickly identify patient specific parameters. The clinical utility of LPN models with many parameters will be greatly enhanced by automated parameter identification, particularly if parameter tuning can match non-invasively obtained clinical data. We present a framework for automated tuning of 0D lumped model parameters to match clinical data. We demonstrate the utility of this framework through application to single ventricle pediatric patients with Norwood physiology. Through a combination of local identifiability, Bayesian estimation and maximum a posteriori simplex optimization, we show the ability to automatically determine physiologically consistent point estimates of the parameters and to quantify uncertainty induced by errors and assumptions in the collected clinical data. We show that multi-level estimation, that is, updating the parameter prior information through sub-model analysis, can lead to a significant reduction in the parameter marginal posterior variance. We first consider virtual patient conditions, with clinical targets generated through model solutions, and second application to a cohort of four single-ventricle patients with Norwood physiology. Copyright © 2016 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/cnm.2799

    View details for PubMedID 27155892

  • SimVascular: An Open Source Pipeline for Cardiovascular Simulation. Annals of biomedical engineering Updegrove, A., Wilson, N. M., Merkow, J., Lan, H., Marsden, A. L., Shadden, S. C. 2017; 45 (3): 525-541


    Patient-specific cardiovascular simulation has become a paradigm in cardiovascular research and is emerging as a powerful tool in basic, translational and clinical research. In this paper we discuss the recent development of a fully open-source SimVascular software package, which provides a complete pipeline from medical image data segmentation to patient-specific blood flow simulation and analysis. This package serves as a research tool for cardiovascular modeling and simulation, and has contributed to numerous advances in personalized medicine, surgical planning and medical device design. The SimVascular software has recently been refactored and expanded to enhance functionality, usability, efficiency and accuracy of image-based patient-specific modeling tools. Moreover, SimVascular previously required several licensed components that hindered new user adoption and code management and our recent developments have replaced these commercial components to create a fully open source pipeline. These developments foster advances in cardiovascular modeling research, increased collaboration, standardization of methods, and a growing developer community.

    View details for DOI 10.1007/s10439-016-1762-8

    View details for PubMedID 27933407

  • Superior performance of continuous over pulsatile flow ventricular assist devices in the single ventricle circulation: A computational study. Journal of biomechanics Schmidt, T., Rosenthal, D., Reinhartz, O., Riemer, K., He, F., Hsia, T., Marsden, A., Kung, E. 2017; 52: 48-54


    This study compares the physiological responses of systemic-to-pulmonary shunted single ventricle patients to pulsatile and continuous flow ventricular assist devices (VADs). Performance differences between pulsatile and continuous flow VADs have been clinically observed, but the underlying mechanism remains poorly understood. Six systemic-to-pulmonary shunted single ventricle patients (mean BSA=0.30m(2)) were computationally simulated using a lumped-parameter network tuned to match patient specific clinical data. A first set of simulations compared current clinical implementation of VADs in single ventricle patients. A second set modified pulsatile flow VAD settings with the goal to optimize cardiac output (CO). For all patients, the best-case continuous flow VAD CO was at least 0.99L/min greater than the optimized pulsatile flow VAD CO (p=0.001). The 25 and 50mL pulsatile flow VADs exhibited incomplete filling at higher heart rates that reduced CO as much as 9.7% and 37.3% below expectations respectively. Optimization of pulsatile flow VAD settings did not achieve statistically significant (p<0.05) improvement to CO. Results corroborate clinical experience that continuous flow VADs produce higher CO and superior ventricular unloading in single ventricle patients. Impaired filling leads to performance degradation of pulsatile flow VADs in the single ventricle circulation.

    View details for DOI 10.1016/j.jbiomech.2016.12.003

    View details for PubMedID 28038771

  • A generalized multi-resolution expansion for uncertainty propagation with application to cardiovascular modeling COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Schiavazzi, D. E., Doostan, A., Iaccarino, G., Marsden, A. L. 2017; 314: 196-221


    Computational models are used in a variety of fields to improve our understanding of complex physical phenomena. Recently, the realism of model predictions has been greatly enhanced by transitioning from deterministic to stochastic frameworks, where the effects of the intrinsic variability in parameters, loads, constitutive properties, model geometry and other quantities can be more naturally included. A general stochastic system may be characterized by a large number of arbitrarily distributed and correlated random inputs, and a limited support response with sharp gradients or event discontinuities. This motivates continued research into novel adaptive algorithms for uncertainty propagation, particularly those handling high dimensional, arbitrarily distributed random inputs and non-smooth stochastic responses. In this work, we generalize a previously proposed multi-resolution approach to uncertainty propagation to develop a method that improves computational efficiency, can handle arbitrarily distributed random inputs and non-smooth stochastic responses, and naturally facilitates adaptivity, i.e., the expansion coefficients encode information on solution refinement. Our approach relies on partitioning the stochastic space into elements that are subdivided along a single dimension, or, in other words, progressive refinements exhibiting a binary tree representation. We also show how these binary refinements are particularly effective in avoiding the exponential increase in the multi-resolution basis cardinality and significantly reduce the regression complexity for moderate to high dimensional random inputs. The performance of the approach is demonstrated through previously proposed uncertainty propagation benchmarks and stochastic multi-scale finite element simulations in cardiovascular flow.

    View details for DOI 10.1016/j.cma.2016.09.024

    View details for Web of Science ID 000392782900012

    View details for PubMedCentralID PMC5568857

  • How successful is successful? Aortic arch shape after successful aortic coarctation repair correlates with left ventricular function JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Brusc, J. L., Khushnood, A., McLeod, K., Biglino, G., Sermesant, M., Pennec, X., Taylor, A. M., Hsia, T., Schievano, S., Khambadkone, S., De Leval, M., Bove, E., Dorfman, A., Baker, G. H., Hlavacek, A., Migliavacca, F., Pennati, G., Dubini, G., Marsden, A., Vignon-Clementel, I., Figliola, R. 2017; 153 (2): 418-427
  • Automated tuning for parameter identification and uncertainty quantification in multi-scale coronary simulations COMPUTERS & FLUIDS Tran, J. S., Schiavazzi, D. E., Ramachandra, A. B., Kahn, A. M., Marsden, A. L. 2017; 142: 128-138


    Atherosclerotic coronary artery disease, which can result in coronary artery stenosis, acute coronary artery occlusion, and eventually myocardial infarction, is a major cause of morbidity and mortality worldwide. Non-invasive characterization of coronary blood flow is important to improve understanding, prevention, and treatment of this disease. Computational simulations can now produce clinically relevant hemodynamic quantities using only non-invasive measurements, combining detailed three dimensional fluid mechanics with physiological models in a multiscale framework. These models, however, require specification of numerous input parameters and are typically tuned manually without accounting for uncertainty in the clinical data, hindering their application to large clinical studies. We propose an automatic, Bayesian, approach to parameter estimation based on adaptive Markov chain Monte Carlo sampling that assimilates non-invasive quantities commonly acquired in routine clinical care, quantifies the uncertainty in the estimated parameters and computes the confidence in local predicted hemodynamic indicators.

    View details for DOI 10.1016/j.compfluid.2016.05.015

    View details for Web of Science ID 000390077800015

    View details for PubMedID 28163340

    View details for PubMedCentralID PMC5287494

  • Computational simulation of postoperative pulmonary flow distribution in Alagille patients with peripheral pulmonary artery stenosis Computational simulation of postoperative pulmonary flow distribution in Alagille patients with peripheral pulmonary artery stenosis Yang, W., Feinstein, J., Marsden, A., Vignon-Clementel, I. 2017; 00: 1–10

    View details for DOI 10.1111/chd.12556

  • SimVascular as an Instructional Tool in the Classroom Goergen, C. J., Shadden, S. C., Marsden, A. L., IEEE IEEE. 2017
  • Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques ANNALS OF VASCULAR SURGERY Ward, E. P., Shiavazzi, D., Sood, D., Marsden, A., Lane, J., Owens, E., Barleben, A. 2017; 38: 151-157
  • A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling. PLoS computational biology Vedula, V., Lee, J., Xu, H., Kuo, C. J., Hsiai, T. K., Marsden, A. L. 2017; 13 (10): e1005828


    Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present a novel computational framework to simulate cardiac hemodynamics in developing zebrafish embryos by coupling 4-D light sheet imaging with a stabilized finite element flow solver, and extract time-dependent mechanical stimuli data. We employ deformable image registration methods to segment the motion of the ventricle from high resolution 4-D light sheet image data. This results in a robust and efficient workflow, as segmentation need only be performed at one cardiac phase, while wall position in the other cardiac phases is found by image registration. Ventricular hemodynamics are then quantified by numerically solving the Navier-Stokes equations in the moving wall domain with our validated flow solver. We demonstrate the applicability of the workflow in wild type zebrafish and three treated fish types that disrupt trabeculation: (a) chemical treatment using AG1478, an ErbB2 signaling inhibitor that inhibits proliferation and differentiation of cardiac trabeculation; (b) injection of gata1a morpholino oligomer (gata1aMO) suppressing hematopoiesis and resulting in attenuated trabeculation; (c) weak-atriumm58 mutant (wea) with inhibited atrial contraction leading to a highly undeveloped ventricle and poor cardiac function. Our simulations reveal elevated wall shear stress (WSS) in wild type and AG1478 compared to gata1aMO and wea. High oscillatory shear index (OSI) in the grooves between trabeculae, compared to lower values on the ridges, in the wild type suggest oscillatory forces as a possible regulatory mechanism of cardiac trabeculation development. The framework has broad applicability for future cardiac developmental studies focused on quantitatively investigating the role of hemodynamic forces and mechanotransduction during morphogenesis.

    View details for DOI 10.1371/journal.pcbi.1005828

    View details for PubMedID 29084212

    View details for PubMedCentralID PMC5679653

  • Assessment of Coronary Artery Aneurysms Caused By Kawasaki Disease Using Transluminal Attenuation Gradient Analysis of CT Angiograms Assessment of Coronary Artery Aneurysms Caused By Kawasaki Disease Using Transluminal Attenuation Gradient Analysis of CT Angiograms Grande Gutierrez, N., Shirinsky, O., Gagarina, N., Lyskina, G., Fukazawa, R., Ogawa, S., Burns, J., Marsden, A., Kahn, A. 2017; 120 (4)
  • Atlas-Based Ventricular Shape Analysis for Understanding Congenital Heart Disease. Progress in pediatric cardiology Farrar, G., Suinesiaputra, A., Gilbert, K., Perry, J. C., Hegde, S., Marsden, A., Young, A. A., Omens, J. H., McCulloch, A. D. 2016; 43: 61-69


    Congenital heart disease is associated with abnormal ventricular shape that can affect wall mechanics and may be predictive of long-term adverse outcomes. Atlas-based parametric shape analysis was used to analyze ventricular geometries of eight adolescent or adult single-ventricle CHD patients with tricuspid atresia and Fontans. These patients were compared with an "atlas" of non-congenital asymptomatic volunteers, resulting in a set of z-scores which quantify deviations from the control population distribution on a patient-by-patient basis. We examined the potential of these scores to: (1) quantify abnormalities of ventricular geometry in single ventricle physiologies relative to the normal population; (2) comprehensively quantify wall motion in CHD patients; and (3) identify possible relationships between ventricular shape and wall motion that may reflect underlying functional defects or remodeling in CHD patients. CHD ventricular geometries at end-diastole and end-systole were individually compared with statistical shape properties of an asymptomatic population from the Cardiac Atlas Project. Shape analysis-derived model properties, and myocardial wall motions between end-diastole and end-systole, were compared with physician observations of clinical functional parameters. Relationships between altered shape and altered function were evaluated via correlations between atlas-based shape and wall motion scores. Atlas-based shape analysis identified a diverse set of specific quantifiable abnormalities in ventricular geometry or myocardial wall motion in all subjects. Moreover, this initial cohort displayed significant relationships between specific shape abnormalities such as increased ventricular sphericity and functional defects in myocardial deformation, such as decreased long-axis wall motion. These findings suggest that atlas-based ventricular shape analysis may be a useful new tool in the management of patients with CHD who are at risk of impaired ventricular wall mechanics and chamber remodeling.

    View details for DOI 10.1016/j.ppedcard.2016.07.010

    View details for PubMedID 28082823

  • Right Ventricular Stroke Work Correlates With Outcomes in Pediatric Pulmonary Arterial Hypertension (PAH) Patients Quality of Care and Outcomes Research Scientific Sessions Yang, W., Marsden, A. L., Ogawa, M. T., Phillips, K. K., Rabinovitch, M., Feinstein, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2016
  • Computed Tomography Fractional Flow Reserve Can Identify Culprit Lesions in Aortoiliac Occlusive Disease Using Minimally Invasive Techniques. Annals of vascular surgery Ward, E. P., Shiavazzi, D., Sood, D., Marsden, A., Lane, J., Owens, E., Barleben, A. 2016


    Currently, the gold standard diagnostic examination for significant aortoiliac lesions is angiography. Fractional flow reserve (FFR) has a growing body of literature in coronary artery disease as a minimally invasive diagnostic procedure. Improvements in numerical hemodynamics have allowed for an accurate and minimally invasive approach to estimating FFR, utilizing cross-sectional imaging. We aim to demonstrate a similar approach to aortoiliac occlusive disease (AIOD).A retrospective review evaluated 7 patients with claudication and cross-sectional imaging showing AIOD. FFR was subsequently measured during conventional angiogram with pull-back pressures in a retrograde fashion. To estimate computed tomography (CT) FFR, CT angiography (CTA) image data were analyzed using the SimVascular software suite to create a computational fluid dynamics model of the aortoiliac system. Inlet flow conditions were derived based on cardiac output, while 3-element Windkessel outlet boundary conditions were optimized to match the expected systolic and diastolic pressures, with outlet resistance distributed based on Murray's law. The data were evaluated with a Student's t-test and receiver operating characteristic curve.All patients had evidence of AIOD on CT and FFR was successfully measured during angiography. The modeled data were found to have high sensitivity and specificity between the measured and CT FFR (P = 0.986, area under the curve = 1). The average difference between the measured and calculated FFRs was 0.136, with a range from 0.03 to 0.30.CT FFR successfully identified aortoiliac lesions with significant pressure drops that were identified with angiographically measured FFR. CT FFR has the potential to provide a minimally invasive approach to identify flow-limiting stenosis for AIOD.

    View details for DOI 10.1016/j.avsg.2016.08.010

    View details for PubMedID 27575305

  • Patient-Specific Simulations Reveal Significant Differences in Mechanical Stimuli in Venous and Arterial Coronary Grafts. Journal of cardiovascular translational research Ramachandra, A. B., Kahn, A. M., Marsden, A. L. 2016; 9 (4): 279-290


    Mechanical stimuli are key to understanding disease progression and clinically observed differences in failure rates between arterial and venous grafts following coronary artery bypass graft surgery. We quantify biologically relevant mechanical stimuli, not available from standard imaging, in patient-specific simulations incorporating non-invasive clinical data. We couple CFD with closed-loop circulatory physiology models to quantify biologically relevant indices, including wall shear, oscillatory shear, and wall strain. We account for vessel-specific material properties in simulating vessel wall deformation. Wall shear was significantly lower (p = 0.014*) and atheroprone area significantly higher (p = 0.040*) in venous compared to arterial grafts. Wall strain in venous grafts was significantly lower (p = 0.003*) than in arterial grafts while no significant difference was observed in oscillatory shear index. Simulations demonstrate significant differences in mechanical stimuli acting on venous vs. arterial grafts, in line with clinically observed graft failure rates, offering a promising avenue for stratifying patients at risk for graft failure.

    View details for DOI 10.1007/s12265-016-9706-0

    View details for PubMedID 27447176

  • On a sparse pressure-flow rate condensation of rigid circulation models. Journal of biomechanics Schiavazzi, D. E., Hsia, T. Y., Marsden, A. L. 2016; 49 (11): 2174-2186


    Cardiovascular simulation has shown potential value in clinical decision-making, providing a framework to assess changes in hemodynamics produced by physiological and surgical alterations. State-of-the-art predictions are provided by deterministic multiscale numerical approaches coupling 3D finite element Navier Stokes simulations to lumped parameter circulation models governed by ODEs. Development of next-generation stochastic multiscale models whose parameters can be learned from available clinical data under uncertainty constitutes a research challenge made more difficult by the high computational cost typically associated with the solution of these models. We present a methodology for constructing reduced representations that condense the behavior of 3D anatomical models using outlet pressure-flow polynomial surrogates, based on multiscale model solutions spanning several heart cycles. Relevance vector machine regression is compared with maximum likelihood estimation, showing that sparse pressure/flow rate approximations offer superior performance in producing working surrogate models to be included in lumped circulation networks. Sensitivities of outlets flow rates are also quantified through a Sobol׳ decomposition of their total variance encoded in the orthogonal polynomial expansion. Finally, we show that augmented lumped parameter models including the proposed surrogates accurately reproduce the response of multiscale models they were derived from. In particular, results are presented for models of the coronary circulation with closed loop boundary conditions and the abdominal aorta with open loop boundary conditions.

    View details for DOI 10.1016/j.jbiomech.2015.11.028

    View details for PubMedID 26671219

  • Uncertainty quantification in virtual surgery hemodynamics predictions for single ventricle palliation INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Schiavazzi, D. E., Arbia, G., Baker, C., Hlavacek, A. M., Hsia, T. Y., Marsden, A. L., Vignon-Clementel, I. E. 2016; 32 (3)


    The adoption of simulation tools to predict surgical outcomes is increasingly leading to questions about the variability of these predictions in the presence of uncertainty associated with the input clinical data. In the present study, we propose a methodology for full propagation of uncertainty from clinical data to model results that, unlike deterministic simulation, enables estimation of the confidence associated with model predictions. We illustrate this problem in a virtual stage II single ventricle palliation surgery example. First, probability density functions (PDFs) of right pulmonary artery (PA) flow split ratio and average pulmonary pressure are determined from clinical measurements, complemented by literature data. Starting from a zero-dimensional semi-empirical approximation, Bayesian parameter estimation is used to find the distributions of boundary conditions that produce the expected PA flow split and average pressure PDFs as pre-operative model results. To reduce computational cost, this inverse problem is solved using a Kriging approximant. Second, uncertainties in the boundary conditions are propagated to simulation predictions. Sparse grid stochastic collocation is employed to statistically characterize model predictions of post-operative hemodynamics in models with and without PA stenosis. The results quantify the statistical variability in virtual surgery predictions, allowing for placement of confidence intervals on simulation outputs.

    View details for DOI 10.1002/cnm.2737

    View details for Web of Science ID 000372155900001

    View details for PubMedID 26217878

  • Computational modeling and engineering in pediatric and congenital heart disease. Current opinion in pediatrics Marsden, A. L., Feinstein, J. A. 2015; 27 (5): 587-596


    Recent methodological advances in computational simulations are enabling increasingly realistic simulations of hemodynamics and physiology, driving increased clinical utility. We review recent developments in the use of computational simulations in pediatric and congenital heart disease, describe the clinical impact in modeling in single-ventricle patients, and provide an overview of emerging areas.Multiscale modeling combining patient-specific hemodynamics with reduced order (i.e., mathematically and computationally simplified) circulatory models has become the de-facto standard for modeling local hemodynamics and 'global' circulatory physiology. We review recent advances that have enabled faster solutions, discuss new methods (e.g., fluid structure interaction and uncertainty quantification), which lend realism both computationally and clinically to results, highlight novel computationally derived surgical methods for single-ventricle patients, and discuss areas in which modeling has begun to exert its influence including Kawasaki disease, fetal circulation, tetralogy of Fallot (and pulmonary tree), and circulatory support.Computational modeling is emerging as a crucial tool for clinical decision-making and evaluation of novel surgical methods and interventions in pediatric cardiology and beyond. Continued development of modeling methods, with an eye towards clinical needs, will enable clinical adoption in a wide range of pediatric and congenital heart diseases.

    View details for DOI 10.1097/MOP.0000000000000269

    View details for PubMedID 26262579

  • In Vitro Assessment of the Assisted Bidirectional Glenn Procedure for Stage One Single Ventricle Repair. Cardiovascular engineering and technology Zhou, J., Esmaily-Moghadam, M., Conover, T. A., Hsia, T., Marsden, A. L., Figliola, R. S. 2015; 6 (3): 256-267


    This in vitro study compares the hemodynamic performance of the Norwood and the Glenn circulations to assess the performance of a novel assisted bidirectional Glenn (ABG) procedure for stage one single ventricle surgery. In the ABG, the flow in a bidirectional Glenn procedure is assisted by injection of a high-energy flow stream from the systemic circulation using an aorta-caval shunt with nozzle. The aim is to explore experimentally the potential of the ABG as a surgical alternative to current surgical practice. The experiments are directly compared against previously published numerical simulations. A multiscale mock circulatory system was used to measure the hemodynamic performance of the three circulations. For each circulation, the system was tested using both low and high values of pulmonary vascular resistance. Resulting parameters measured were: pressure and flow rate at left/right pulmonary artery and superior vena cava (SVC). Systemic oxygen delivery (OD) was calculated. A parametric study of the ratio of ABG nozzle to shunt diameter was done. We report time-based comparisons with numerical simulations for the three surgical variants tested. The ABG circulation demonstrated an increase of 30-38% in pulmonary flow with a 2-3.7 mmHg increase in SVC pressure compared to the Glenn and a 4-14% higher systemic OD than either the Norwood or the Glenn. The nozzle/shunt diameter ratio affected the local hemodynamics. These experimental results agreed with those of the numerical model: mean flow values were not significantly different (p > 0.05) while mean pressures were comparable within 1.2 mmHg. The results verify the approaches providing two tools to study this complicated circulation. Using a realistic experimental model we demonstrate the performance of a novel surgical procedure with potential to improve patient hemodynamics in early palliation of the univentricular circulation.

    View details for DOI 10.1007/s13239-015-0232-z

    View details for PubMedID 26577359

  • Integration of Clinical Data Collected at Different Times for Virtual Surgery in Single Ventricle Patients: A Case Study ANNALS OF BIOMEDICAL ENGINEERING Corsini, C., Baker, C., Baretta, A., Biglino, G., Hlavacek, A. M., Hsia, T., Kung, E., Marsden, A., Migliavacca, F., Vignon-Clementel, I., Pennati, G. 2015; 43 (6): 1310-1320


    Newborns with single ventricle physiology are usually palliated with a multi-staged procedure. When cardiovascular complications e.g., collateral vessel formation occur during the inter-stage periods, further treatments are required. An 8-month-old patient, who underwent second stage (i.e., bi-directional Glenn, BDG) surgery at 4 months, was diagnosed with a major veno-venous collateral vessel (VVC) which was endovascularly occluded to improve blood oxygen saturations. Few clinical data were collected at 8 months, whereas at 4 months a more detailed data set was available. The aim of this study is threefold: (i) to show how to build a patient-specific model describing the hemodynamics in the presence of VVC, using patient-specific clinical data collected at different times; (ii) to use this model to perform virtual VVC occlusion for quantitative hemodynamics prediction; and (iii) to compare predicted hemodynamics with post-operative measurements. The three-dimensional BDG geometry, resulting from the virtual surgery on the first stage model, was coupled with a lumped parameter model (LPM) of the 8-month patient's circulation. The latter was developed by scaling the 4-month LPM to account for changes in vascular impedances due to growth and adaptation. After virtual VVC closure, the model confirmed the 2 mmHg BDG pressure increase, as clinically observed, suggesting the importance of modeling vascular adaptation following the BDG procedure.

    View details for DOI 10.1007/s10439-014-1113-6

    View details for Web of Science ID 000355924000005

    View details for PubMedID 25344350

  • Computational Modeling of Pathophysiologic Responses to Exercise in Fontan Patients ANNALS OF BIOMEDICAL ENGINEERING Kung, E., Perry, J. C., Davis, C., Migliavacca, F., Pennati, G., Giardini, A., Hsia, T., Marsden, A. 2015; 43 (6): 1335-1347


    Reduced exercise capacity is nearly universal among Fontan patients. Although many factors have emerged as possible contributors, the degree to which each impacts the overall hemodynamics is largely unknown. Computational modeling provides a means to test hypotheses of causes of exercise intolerance via precisely controlled virtual experiments and measurements. We quantified the physiological impacts of commonly encountered, clinically relevant dysfunctions introduced to the exercising Fontan system via a previously developed lumped-parameter model of Fontan exercise. Elevated pulmonary arterial pressure was observed in all cases of dysfunction, correlated with lowered cardiac output (CO), and often mediated by elevated atrial pressure. Pulmonary vascular resistance was not the most significant factor affecting exercise performance as measured by CO. In the absence of other dysfunctions, atrioventricular valve insufficiency alone had significant physiological impact, especially under exercise demands. The impact of isolated dysfunctions can be linearly summed to approximate the combined impact of several dysfunctions occurring in the same system. A single dominant cause of exercise intolerance was not identified, though several hypothesized dysfunctions each led to variable decreases in performance. Computational predictions of performance improvement associated with various interventions should be weighed against procedural risks and potential complications, contributing to improvements in routine patient management protocol.

    View details for DOI 10.1007/s10439-014-1131-4

    View details for Web of Science ID 000355924000007

    View details for PubMedID 25260878

  • Multiscale Modeling of Cardiovascular Flows for Clinical Decision Support APPLIED MECHANICS REVIEWS Marsden, A. L., Esmaily-Moghadam, M. 2015; 67 (3)

    View details for DOI 10.1115/1.4029909

    View details for Web of Science ID 000360285400004

  • Distribution of aerosolized particles in healthy and emphysematous rat lungs: Comparison between experimental and numerical studies JOURNAL OF BIOMECHANICS Oakes, J. M., Marsden, A. L., Grandmont, C., Darquenne, C., Vignon-Clementel, I. E. 2015; 48 (6): 1147-1157


    In silico models of airflow and particle deposition in the lungs are increasingly used to determine the therapeutic or toxic effects of inhaled aerosols. While computational methods have advanced significantly, relatively few studies have directly compared model predictions to experimental data. Furthermore, few prior studies have examined the influence of emphysema on particle deposition. In this work we performed airflow and particle simulations to compare numerical predictions to data from our previous aerosol exposure experiments. Employing an image-based 3D rat airway geometry, we first compared steady flow simulations to coupled 3D-0D unsteady simulations in the healthy rat lung. Then, in 3D-0D simulations, the influence of emphysema was investigated by matching disease location to the experimental study. In both the healthy unsteady and steady simulations, good agreement was found between numerical predictions of aerosol delivery and experimental deposition data. However, deposition patterns in the 3D geometry differed between the unsteady and steady cases. On the contrary, satisfactory agreement was not found between the numerical predictions and experimental data for the emphysematous lungs. This indicates that the deposition rate downstream of the 3D geometry is likely proportional to airflow delivery in the healthy lungs, but not in the emphysematous lungs. Including small airway collapse, variations in downstream airway size and tissue properties, and tracking particles throughout expiration may result in a more favorable agreement in future studies.

    View details for DOI 10.1016/j.jbiomech.2015.01.004

    View details for Web of Science ID 000352672100036

    View details for PubMedID 25682537

  • A bi-partitioned iterative algorithm for solving linear systems arising from incompressible flow problems COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Esmaily-Moghadam, M., Bazilevs, Y., Marsden, A. L. 2015; 286: 40-62
  • Simulations Reveal Adverse Hemodynamics in Patients With Multiple Systemic to Pulmonary Shunts JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Esmaily-Moghadam, M., Murtuza, B., Hsia, T., Marsden, A. 2015; 137 (3)


    For newborns diagnosed with pulmonary atresia or severe pulmonary stenosis leading to insufficient pulmonary blood flow, cyanosis can be mitigated with placement of a modified Blalock-Taussig shunt (MBTS) between the innominate and pulmonary arteries. In some clinical scenarios, patients receive two systemic-to-pulmonary connections, either by leaving the patent ductus arteriosus (PDA) open or by adding an additional central shunt (CS) in conjunction with the MBTS. This practice has been motivated by the thinking that an additional source of pulmonary blood flow could beneficially increase pulmonary flow and provide the security of an alternate pathway in case of thrombosis. However, there have been clinical reports of premature shunt occlusion when more than one shunt is employed, leading to speculation that multiple shunts may in fact lead to unfavorable hemodynamics and increased mortality. In this study, we hypothesize that multiple shunts may lead to undesirable flow competition, resulting in increased residence time (RT) and elevated risk of thrombosis, as well as pulmonary overcirculation. Computational fluid dynamics-based multiscale simulations were performed to compare a range of shunt configurations and systematically quantify flow competition, pulmonary circulation, and other clinically relevant parameters. In total, 23 cases were evaluated by systematically changing the PDA/CS diameter, pulmonary vascular resistance (PVR), and MBTS position and compared by quantifying oxygen delivery (OD) to the systemic and coronary beds, wall shear stress (WSS), oscillatory shear index (OSI), WSS gradient (WSSG), and RT in the pulmonary artery (PA), and MBTS. Results showed that smaller PDA/CS diameters can lead to flow conditions consistent with increased thrombus formation due to flow competition in the PA, and larger PDA/CS diameters can lead to insufficient OD due to pulmonary hyperfusion. In the worst case scenario, it was found that multiple shunts can lead to a 160% increase in RT and a 10% decrease in OD. Based on the simulation results presented in this study, clinical outcomes for patients receiving multiple shunts should be critically investigated, as this practice appears to provide no benefit in terms of OD and may actually increase thrombotic risk.

    View details for DOI 10.1115/1.4029429

    View details for Web of Science ID 000350572600002

    View details for PubMedID 25531794

  • Computational Simulation of the Adaptive Capacity of Vein Grafts in Response to Increased Pressure JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Ramachandra, A. B., Sankaran, S., Humphrey, J. D., Marsden, A. L. 2015; 137 (3)


    Vein maladaptation, leading to poor long-term patency, is a serious clinical problem in patients receiving coronary artery bypass grafts (CABGs) or undergoing related clinical procedures that subject veins to elevated blood flow and pressure. We propose a computational model of venous adaptation to altered pressure based on a constrained mixture theory of growth and remodeling (G&R). We identify constitutive parameters that optimally match biaxial data from a mouse vena cava, then numerically subject the vein to altered pressure conditions and quantify the extent of adaptation for a biologically reasonable set of bounds for G&R parameters. We identify conditions under which a vein graft can adapt optimally and explore physiological constraints that lead to maladaptation. Finally, we test the hypothesis that a gradual, rather than a step, change in pressure will reduce maladaptation. Optimization is used to accelerate parameter identification and numerically evaluate hypotheses of vein remodeling.

    View details for DOI 10.1115/1.4029021

    View details for Web of Science ID 000350572600010

    View details for PubMedID 25376151

  • The assisted bidirectional Glenn: A novel surgical approach for first-stage single-ventricle heart palliation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Esmaily-Moghadam, M., Hsia, T., Marsden, A. L. 2015; 149 (3): 699-705


    Outcomes after a modified Blalock-Taussig shunt (mBTS) in neonates with single-ventricle physiology remain unsatisfactory. However, initial palliation with a superior cavopulmonary connection, such as a bidirectional Glenn (BDG), is discouraged, owing to potential for inadequate pulmonary blood flow (PBF). We tested the feasibility of a novel surgical approach, adopting the engineering concept of an ejector pump, whereby the flow in the BDG is "assisted" by injection of a high-energy flow stream from the systemic circulation.Realistic 3-dimensional models of the neonatal mBTS and BDG circulations were created. The "assisted" bidirectional Glenn (ABG) consisted of a shunt between the right innominate artery and the superior vena cava (SVC), with a 1.5-mm clip near the SVC anastomosis to create a Venturi effect. The 3 models were coupled to a validated hydraulic circulation model, and 2 pulmonary vascular resistance (PVR) values (7 and 2.3 Wood units) were simulated.The ABG provided the highest systemic oxygen saturation and oxygen delivery at both PVR levels. In addition to achieving higher PBF than the BDG, the ABG produced a lower single-ventricular workload than mBTS. SVC pressure was highest in the ABG model (ABG: 15; Glenn: 11; mBTS: 3 mm Hg; PVR = 7 Wood units), but at low PVR, the SVC pressure was significantly lower (ABG: 8; Glenn: 6; mBTS: <3 mm Hg).Adopting the principle of an ejector pump, with additional flow directed into the SVC in a BDG, the ABG appears to increase PBF with a modest increase in SVC and pulmonary arterial pressure. Although multiscale modeling results demonstrate the conceptual feasibility of the ABG circulation, further technical refinement and investigations are necessary, especially in an appropriate animal model.

    View details for DOI 10.1016/j.jtcvs.2014.10.035

    View details for Web of Science ID 000351930600027

    View details for PubMedID 25454920

  • Hemodynamic effects of left pulmonary artery stenosis after superior cavopulmonary connection: A patient-specific multiscale modeling study JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Schiavazzi, D. E., Kung, E. O., Marsden, A. L., Baker, C., Pennati, G., Hsia, T., Hlavacek, A., Dorfman, A. L. 2015; 149 (3): 689-?


    Currently, no quantitative guidelines have been established for treatment of left pulmonary artery (LPA) stenosis. This study aims to quantify the effects of LPA stenosis on postoperative hemodynamics for single-ventricle patients undergoing stage II superior cavopulmonary connection (SCPC) surgery, using a multiscale computational approach.Image data from 6 patients were segmented to produce 3-dimensional models of the pulmonary arteries before stage II surgery. Pressure and flow measurements were used to tune a 0-dimensional model of the entire circulation. Postoperative geometries were generated through stage II virtual surgery; varying degrees of LPA stenosis were applied using mesh morphing and hemodynamics assessed through coupled 0-3-dimensional simulations. To relate metrics of stenosis to clinical classifications, pediatric cardiologists and surgeons ranked the degrees of stenosis in the models. The effects of LPA stenosis were assessed based on left-to-right pulmonary artery flow split ratios, mean pressure drop across the stenosis, cardiac pressure-volume loops, and other clinically relevant parameters.Stenosis of >65% of the vessel diameter was required to produce a right pulmonary artery:LPA flow split <30%, and/or a mean pressure drop of >3.0 mm Hg, defined as clinically significant changes.The effects of <65% stenosis on SCPC hemodynamics and physiology were minor and may not justify the increased complexity of adding LPA arterioplasty to the SCPC operation. However, in the longer term, pulmonary augmentation may affect outcomes of the Fontan completion surgery, as pulmonary artery distortion is a risk factor that may influence stage III physiology.

    View details for DOI 10.1016/j.jtcvs.2014.12.040

    View details for Web of Science ID 000351930600025

    View details for PubMedID 25659189

  • Flow simulations and validation for the first cohort of patients undergoing the Y-graft Fontan procedure JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, W., Chan, F. P., Reddy, V. M., Marsden, A. L., Feinstein, J. A. 2015; 149 (1): 247-255


    In this study, with the use of computational fluid dynamics, we evaluate the postoperative hemodynamic performance of the first cohort of patients undergoing a handcrafted Y-graft Fontan procedure and validate simulation predictions of hepatic blood flow distribution against in vivo clinical data.An 18-12 × 2-mm handcrafted Y-graft modification of the Fontan procedure was performed in 6 patients. Early (at the time of discharge) and 6-month postoperative 3-dimensional magnetic resonance imaging data were collected. Patient-specific models were constructed for flow simulations.Hepatic blood flow distribution varied among patients. Lung perfusion data (n = 3) showed good agreement with simulations. Postoperative asymmetry in hepatic blood flow distribution was reduced 6 months postoperatively. In 1 patient, low wall shear stress was found in the left limb of the Y-graft, corresponding to the location of subsequent thrombosis in the patient.The credibility and accuracy of simulation-based predictions of postoperative hepatic flow distribution for the Fontan surgery have been validated by in vivo lung perfusion data. The performance of the Y-graft design is highly patient-specific. The anastomosis location is likely the most important factor influencing hepatic blood flow distribution. Although the development of thrombosis is multifactorial, the occurrence in 1 patient suggests that simulations should not solely consider the hepatic blood flow distribution but also aim to avoid low wall shear stress in the limbs.

    View details for DOI 10.1016/j.jtcvs.2014.08.069

    View details for PubMedID 25439766

  • Impact of data distribution on the parallel performance of iterative linear solvers with emphasis on CFD of incompressible flows COMPUTATIONAL MECHANICS Esmaily-Moghadam, M., Bazilevs, Y., Marsden, A. L. 2015; 55 (1): 93-103
  • Technical feasibility and intermediate outcomes of using a handcrafted, area-preserving, bifurcated Y-graft modification of the Fontan procedure JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Martin, M. H., Feinstein, J. A., Chan, F. P., Marsden, A. L., Yang, W., Reddy, V. M. 2015; 149 (1): 239-U381


    To demonstrate the technical feasibility and describe intermediate outcomes for the initial patients undergoing handcrafted, area-preserving, Y-graft modification of the Fontan procedure.A retrospective review of a pilot study was undertaken to describe preoperative, intraoperative, and postoperative results.Six patients underwent successful procedures and remain alive 3 to 4 years later. The median age at operation was 3.3 years, and median weight was 13.2 kg. Five operations were done without cardiopulmonary bypass and no intraoperative pressure gradients were found. Five patients were extubated by postoperative day 1, Fontan pressures were 12 to 14 mm Hg, transpulmonary gradients were 6 to 8 mm Hg, and no renal or hepatic function abnormalities were found. Length of stay was 10 to 64 days. One patient required venovenous extracorporeal membrane oxygenation for previously undiagnosed plastic bronchitis (64-day stay); another required reoperation for an incidentally diagnosed aortic thrombus (44-day stay). One patient had occlusion of a Y-graft limb noted on magnetic resonance imaging follow-up at 3 months. Catheterization showed excellent hemodynamic parameters and no Fontan obstruction. Occlusion was believed to be due to right-sided pulmonary arteriovenous malformations and widely discrepant flow (80%) to the right lung leading to low flow in the left limb.The area-preserving, bifurcated Y-graft Fontan modification is technically feasible and shows excellent intermediate outcomes. Additional study is required to determine whether the advantages seen in the computational models will be realized in patients over the long-term, and to optimize patient selection for each of the various Fontan options now available.

    View details for DOI 10.1016/j.jtcvs.2014.08.058

    View details for Web of Science ID 000350550100068

    View details for PubMedID 25439786

  • Technical feasibility and intermediate outcomes of using a handcrafted, area-preserving, bifurcated Y-graft modification of the Fontan procedure. journal of thoracic and cardiovascular surgery Martin, M. H., Feinstein, J. A., Chan, F. P., Marsden, A. L., Yang, W., Reddy, V. M. 2015; 149 (1): 239-45 e1


    To demonstrate the technical feasibility and describe intermediate outcomes for the initial patients undergoing handcrafted, area-preserving, Y-graft modification of the Fontan procedure.A retrospective review of a pilot study was undertaken to describe preoperative, intraoperative, and postoperative results.Six patients underwent successful procedures and remain alive 3 to 4 years later. The median age at operation was 3.3 years, and median weight was 13.2 kg. Five operations were done without cardiopulmonary bypass and no intraoperative pressure gradients were found. Five patients were extubated by postoperative day 1, Fontan pressures were 12 to 14 mm Hg, transpulmonary gradients were 6 to 8 mm Hg, and no renal or hepatic function abnormalities were found. Length of stay was 10 to 64 days. One patient required venovenous extracorporeal membrane oxygenation for previously undiagnosed plastic bronchitis (64-day stay); another required reoperation for an incidentally diagnosed aortic thrombus (44-day stay). One patient had occlusion of a Y-graft limb noted on magnetic resonance imaging follow-up at 3 months. Catheterization showed excellent hemodynamic parameters and no Fontan obstruction. Occlusion was believed to be due to right-sided pulmonary arteriovenous malformations and widely discrepant flow (80%) to the right lung leading to low flow in the left limb.The area-preserving, bifurcated Y-graft Fontan modification is technically feasible and shows excellent intermediate outcomes. Additional study is required to determine whether the advantages seen in the computational models will be realized in patients over the long-term, and to optimize patient selection for each of the various Fontan options now available.

    View details for DOI 10.1016/j.jtcvs.2014.08.058

    View details for PubMedID 25439786

  • Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease BIOMECHANICS AND MODELING IN MECHANOBIOLOGY Sengupta, D., Kahn, A. M., Kung, E., Moghadam, M. E., Shirinsky, O., Lyskina, G. A., Burns, J. C., Marsden, A. L. 2014; 13 (6): 1261-1276


    Kawasaki disease (KD) is the leading cause of acquired heart disease in children and can result in life-threatening coronary artery aneurysms in up to 25 % of patients. These aneurysms put patients at risk of thrombus formation, myocardial infarction, and sudden death. Clinicians must therefore decide which patients should be treated with anticoagulant medication, and/or surgical or percutaneous intervention. Current recommendations regarding initiation of anticoagulant therapy are based on anatomy alone with historical data suggesting that patients with aneurysms [Formula: see text]8 mm are at greatest risk of thrombosis. Given the multitude of variables that influence thrombus formation, we postulated that hemodynamic data derived from patient-specific simulations would more accurately predict risk of thrombosis than maximum diameter alone. Patient-specific blood flow simulations were performed on five KD patients with aneurysms and one KD patient with normal coronary arteries. Key hemodynamic and geometric parameters, including wall shear stress, particle residence time, and shape indices, were extracted from the models and simulations and compared with clinical outcomes. Preliminary fluid structure interaction simulations with radial expansion were performed, revealing modest differences in wall shear stress compared to the rigid wall case. Simulations provide compelling evidence that hemodynamic parameters may be a more accurate predictor of thrombotic risk than aneurysm diameter alone and motivate the need for follow-up studies with a larger cohort. These results suggest that a clinical index incorporating hemodynamic information be used in the future to select patients for anticoagulant therapy.

    View details for DOI 10.1007/s10237-014-0570-z

    View details for Web of Science ID 000343210900008

    View details for PubMedID 24722951

  • ST and ALE-VMS methods for patient-specific cardiovascular fluid mechanics modeling MATHEMATICAL MODELS & METHODS IN APPLIED SCIENCES Takizawa, K., Bazilevs, Y., Tezduyar, T. E., Long, C. C., Marsden, A. L., Schjodt, K. 2014; 24 (12)
  • Shape optimization of pulsatile ventricular assist devices using FSI to minimize thrombotic risk COMPUTATIONAL MECHANICS Long, C. C., Marsden, A. L., Bazilevs, Y. 2014; 54 (4): 921-932
  • Computation of residence time in the simulation of pulsatile ventricular assist devices COMPUTATIONAL MECHANICS Long, C. C., Esmaily-Moghadam, M., Marsden, A. L., Bazilevs, Y. 2014; 54 (4): 911-919
  • USNCTAM perspectives on mechanics in medicine JOURNAL OF THE ROYAL SOCIETY INTERFACE Bao, G., Bazilevs, Y., Chung, J., Decuzzi, P., Espinosa, H. D., Ferrari, M., Gao, H., Hossain, S. S., Hughes, T. J., Kamm, R. D., Liu, W. K., Marsden, A., Schrefler, B. 2014; 11 (97)


    Over decades, the theoretical and applied mechanics community has developed sophisticated approaches for analysing the behaviour of complex engineering systems. Most of these approaches have targeted systems in the transportation, materials, defence and energy industries. Applying and further developing engineering approaches for understanding, predicting and modulating the response of complicated biomedical processes not only holds great promise in meeting societal needs, but also poses serious challenges. This report, prepared for the US National Committee on Theoretical and Applied Mechanics, aims to identify the most pressing challenges in biological sciences and medicine that can be tackled within the broad field of mechanics. This echoes and complements a number of national and international initiatives aiming at fostering interdisciplinary biomedical research. This report also comments on cultural/educational challenges. Specifically, this report focuses on three major thrusts in which we believe mechanics has and will continue to have a substantial impact. (i) Rationally engineering injectable nano/microdevices for imaging and therapy of disease. Within this context, we discuss nanoparticle carrier design, vascular transport and adhesion, endocytosis and tumour growth in response to therapy, as well as uncertainty quantification techniques to better connect models and experiments. (ii) Design of biomedical devices, including point-of-care diagnostic systems, model organ and multi-organ microdevices, and pulsatile ventricular assistant devices. (iii) Mechanics of cellular processes, including mechanosensing and mechanotransduction, improved characterization of cellular constitutive behaviour, and microfluidic systems for single-cell studies.

    View details for DOI 10.1098/rsif.2014.0301

    View details for Web of Science ID 000338436200008

    View details for PubMedID 24872502

  • A Simulation Protocol for Exercise Physiology in Fontan Patients Using a Closed Loop Lumped-Parameter Model JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Kung, E., Pennati, G., Migliavacca, F., Hsia, T., Figliola, R., Marsden, A., Giardini, A. 2014; 136 (8)


    Reduced exercise capacity is nearly universal among Fontan patients, though its etiology is not yet fully understood. While previous computational studies have attempted to model Fontan exercise, they did not fully account for global physiologic mechanisms nor directly compare results against clinical and physiologic data.In this study, we developed a protocol to simulate Fontan lower-body exercise using a closed-loop lumped-parameter model describing the entire circulation. We analyzed clinical exercise data from a cohort of Fontan patients, incorporated previous clinical findings from literature, quantified a comprehensive list of physiological changes during exercise, translated them into a computational model of the Fontan circulation, and designed a general protocol to model Fontan exercise behavior. Using inputs of patient weight, height, and if available, patient-specific reference heart rate (HR) and oxygen consumption, this protocol enables the derivation of a full set of parameters necessary to model a typical Fontan patient of a given body-size over a range of physiologic exercise levels.In light of previous literature data and clinical knowledge, the model successfully produced realistic trends in physiological parameters with exercise level. Applying this method retrospectively to a set of clinical Fontan exercise data, direct comparison between simulation results and clinical data demonstrated that the model successfully reproduced the average exercise response of a cohort of typical Fontan patients.This work is intended to offer a foundation for future advances in modeling Fontan exercise, highlight the needs in clinical data collection, and provide clinicians with quantitative reference exercise physiologies for Fontan patients.

    View details for DOI 10.1115/1.4027271

    View details for Web of Science ID 000338507000007

    View details for PubMedID 24658635

  • In Vitro Validation of Patient-Specific Hemodynamic Simulations in Coronary Aneurysms Caused by Kawasaki Disease. Cardiovascular engineering and technology Kung, E., Kahn, A. M., Burns, J. C., Marsden, A. 2014; 5 (2): 189-201


    To perform experimental validation of computational fluid dynamics (CFD) applied to patient specific coronary aneurysm anatomy of Kawasaki disease. We quantified hemodynamics in a patient-specific coronary artery aneurysm physical phantom under physiologic rest and exercise flow conditions. Using phase contrast MRI (PCMRI), we acquired 3-component flow velocity at two slice locations in the aneurysms. We then performed numerical simulations with the same geometry and inflow conditions, and performed qualitative and quantitative comparisons of velocities between experimental measurements and simulation results. We observed excellent qualitative agreement in flow pattern features. The quantitative spatially and temporally varying differences in velocity between PCMRI and CFD were proportional to the flow velocity. As a result, the percent discrepancy between simulation and experiment was relatively constant regardless of flow velocity variations. Through 1D and 2D quantitative comparisons, we found a 5-17% difference between measured and simulated velocities. Additional analysis assessed wall shear stress differences between deformable and rigid wall simulations. This study demonstrated that CFD produced good qualitative and quantitative predictions of velocities in a realistic coronary aneurysm anatomy under physiological flow conditions. The results provide insights on factors that may influence the level of agreement, and a set of in vitro experimental data that can be used by others to compare against CFD simulation results. The findings of this study increase confidence in the use of CFD for investigating hemodynamics in the specialized anatomy of coronary aneurysms. This provides a basis for future hemodynamics studies in patient-specific models of Kawasaki disease.

    View details for PubMedID 25050140

  • In Vitro Validation of Patient-Specific Hemodynamic Simulations in Coronary Aneurysms Caused by Kawasaki Disease CARDIOVASCULAR ENGINEERING AND TECHNOLOGY Kung, E., Kahn, A. M., Burns, J. C., Marsden, A. 2014; 5 (2): 189-201
  • Airflow and Particle Deposition Simulations in Health and Emphysema: From In Vivo to In Silico Animal Experiments ANNALS OF BIOMEDICAL ENGINEERING Oakes, J. M., Marsden, A. L., Grandmont, C., Shadden, S. C., Darquenne, C., Vignon-Clementel, I. E. 2014; 42 (4): 899-914


    Image-based in silico modeling tools provide detailed velocity and particle deposition data. However, care must be taken when prescribing boundary conditions to model lung physiology in health or disease, such as in emphysema. In this study, the respiratory resistance and compliance were obtained by solving an inverse problem; a 0D global model based on healthy and emphysematous rat experimental data. Multi-scale CFD simulations were performed by solving the 3D Navier-Stokes equations in an MRI-derived rat geometry coupled to a 0D model. Particles with 0.95 μm diameter were tracked and their distribution in the lung was assessed. Seven 3D-0D simulations were performed: healthy, homogeneous, and five heterogeneous emphysema cases. Compliance (C) was significantly higher (p = 0.04) in the emphysematous rats (C = 0.37 ± 0.14 cm(3)/cmH2O) compared to the healthy rats (C = 0.25 ± 0.04 cm(3)/cmH2O), while the resistance remained unchanged (p = 0.83). There were increases in airflow, particle deposition in the 3D model, and particle delivery to the diseased regions for the heterogeneous cases compared to the homogeneous cases. The results highlight the importance of multi-scale numerical simulations to study airflow and particle distribution in healthy and diseased lungs. The effect of particle size and gravity were studied. Once available, these in silico predictions may be compared to experimental deposition data.

    View details for DOI 10.1007/s10439-013-0954-8

    View details for Web of Science ID 000333010900018

    View details for PubMedID 24318192

  • Recent advances in computational methodology for simulation of mechanical circulatory assist devices WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE Marsden, A. L., Bazilevs, Y., Long, C. C., Behr, M. 2014; 6 (2): 169-188


    Ventricular assist devices (VADs) provide mechanical circulatory support to offload the work of one or both ventricles during heart failure. They are used in the clinical setting as destination therapy, as bridge to transplant, or more recently as bridge to recovery to allow for myocardial remodeling. Recent developments in computational simulation allow for detailed assessment of VAD hemodynamics for device design and optimization for both children and adults. Here, we provide a focused review of the recent literature on finite element methods and optimization for VAD simulations. As VAD designs typically fall into two categories, pulsatile and continuous flow devices, we separately address computational challenges of both types of designs, and the interaction with the circulatory system with three representative case studies. In particular, we focus on recent advancements in finite element methodology that have increased the fidelity of VAD simulations. We outline key challenges, which extend to the incorporation of biological response such as thrombosis and hemolysis, as well as shape optimization methods and challenges in computational methodology.

    View details for DOI 10.1002/wsbm.1260

    View details for Web of Science ID 000333535500004

    View details for PubMedID 24449607

  • Optimization in Cardiovascular Modeling ANNUAL REVIEW OF FLUID MECHANICS, VOL 46 Marsden, A. L. 2014; 46: 519-546
  • An integrated approach to patient-specific predictive modeling for single ventricle heart palliation COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING Corsini, C., Baker, C., Kung, E., Schievano, S., Arbia, G., Baretta, A., Biglino, G., Migliavacca, F., Dubini, G., Pennati, G., Marsden, A., Vignon-Clementel, I., Taylor, A., Hsia, T., Dorfman, A. 2014; 17 (14): 1572-1589


    In patients with congenital heart disease and a single ventricle (SV), ventricular support of the circulation is inadequate, and staged palliative surgery (usually 3 stages) is needed for treatment. In the various palliative surgical stages individual differences in the circulation are important and patient-specific surgical planning is ideal. In this study, an integrated approach between clinicians and engineers has been developed, based on patient-specific multi-scale models, and is here applied to predict stage 2 surgical outcomes. This approach involves four distinct steps: (1) collection of pre-operative clinical data from a patient presenting for SV palliation, (2) construction of the pre-operative model, (3) creation of feasible virtual surgical options which couple a three-dimensional model of the surgical anatomy with a lumped parameter model (LPM) of the remainder of the circulation and (4) performance of post-operative simulations to aid clinical decision making. The pre-operative model is described, agreeing well with clinical flow tracings and mean pressures. Two surgical options (bi-directional Glenn and hemi-Fontan operations) are virtually performed and coupled to the pre-operative LPM, with the hemodynamics of both options reported. Results are validated against postoperative clinical data. Ultimately, this work represents the first patient-specific predictive modeling of stage 2 palliation using virtual surgery and closed-loop multi-scale modeling.

    View details for DOI 10.1080/10255842.2012.758254

    View details for Web of Science ID 000337528400005

    View details for PubMedID 23343002

  • Numerical blood flow simulation in surgical corrections: what do we need for an accurate analysis? JOURNAL OF SURGICAL RESEARCH Arbia, G., Corsini, C., Moghadam, M. E., Marsden, A. L., Migliavacca, F., Pennati, G., Hsia, T., Vignon-Clementel, I. E. 2014; 186 (1): 44-55


    Computational fluid dynamics has been increasingly used in congenital heart surgery to simulate pathophysiological blood flow, investigate surgical options, or design medical devices. Several commercial and research computational or numerical codes have been developed. They present different approaches to numerically solve the blood flow equations, raising the question whether these numerical codes are equally reliable to achieve accurate simulation results. Accordingly, we sought to examine the influence of numerical code selection in several complex congenital cardiac operations.The main steps of blood flow simulations are detailed (geometrical mesh, boundary conditions, and solver numerical methods) for congenital cardiac operations of increasing complexity. The first case tests different numerical solutions against an analytical, or exact, solution. In the second case, the three-dimensional domain is a patient-specific superior cavopulmonary anastomosis. As an analytical solution does not exist in such a complex geometry, different numerical solutions are compared. Finally, a realistic case of a systemic-to-pulmonary shunt is presented with both geometrically and physiologically challenging conditions. For all, solutions from a commercially available code and an open-source research code are compared.In the first case, as the mesh or solver numerical method is refined, the simulation results for both codes converged to the analytical solution. In the second example, velocity differences between the two codes are greater when the resolution of the mesh were lower and less refined. The third case with realistic anatomy reveals that the pulsatile complex flow is very similar for both codes.The precise setup of the numerical cases has more influence on the results than the choice of numerical codes. The need for detailed construction of the numerical model that requires high computational cost depends on the precision needed to answer the biomedical question at hand and should be assessed for each problem on a combination of clinically relevant patient-specific geometry and physiological conditions.

    View details for DOI 10.1016/j.jss.2013.07.037

    View details for Web of Science ID 000328628800007

    View details for PubMedID 23993199

  • A new preconditioning technique for implicitly coupled multidomain simulations with applications to hemodynamics COMPUTATIONAL MECHANICS Esmaily-Moghadam, M., Bazilevs, Y., Marsden, A. L. 2013; 52 (5): 1141-1152
  • Fluid-structure interaction simulation of pulsatile ventricular assist devices COMPUTATIONAL MECHANICS Long, C. C., Marsden, A. L., Bazilevs, Y. 2013; 52 (5): 971-981
  • A non-discrete method for computation of residence time in fluid mechanics simulations PHYSICS OF FLUIDS Esmaily-Moghadam, M., Hsia, T., Marsden, A. L. 2013; 25 (11)

    View details for DOI 10.1063/1.4819142

    View details for Web of Science ID 000329184100003

  • Simulation based planning of surgical interventions in pediatric cardiology PHYSICS OF FLUIDS Marsden, A. L. 2013; 25 (10)

    View details for DOI 10.1063/1.4825031

    View details for Web of Science ID 000326642800003

  • Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis PLOS ONE Lee, J., Moghadam, M. E., Kung, E., Cao, H., Beebe, T., Miller, Y., Roman, B. L., Lien, C., Chi, N. C., Marsden, A. L., Hsiai, T. K. 2013; 8 (8)


    Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP) (y1) transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

    View details for DOI 10.1371/journal.pone.0072924

    View details for Web of Science ID 000324403200035

    View details for PubMedID 24009714

  • A modular numerical method for implicit 0D/3D coupling in cardiovascular finite element simulations JOURNAL OF COMPUTATIONAL PHYSICS Moghadam, M. E., Vignon-Clementel, I. E., Figliola, R., Marsden, A. L. 2013; 244: 63-79
  • Lagrangian analysis of hemodynamics data from FSI simulation INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Duvernois, V., Marsden, A. L., Shadden, S. C. 2013; 29 (4): 445-461


    We present the computation of lagrangian-based flow characterization measures for time-dependent, deformable-wall, finite-element blood flow simulations. Applicability of the algorithm is demonstrated in a fluid-structure interaction simulation of blood flow through a total cavopulmonary connection (Fontan procedure), and results are compared with a rigid-vessel simulation. Specifically, we report on several important lagrangian-based measures including flow distributions, finite-time Lyapunov exponent fields, particle residence time, and exposure time calculations. Overall, strong similarity in lagrangian measures of the flow between deformable and rigid-vessel models was observed.

    View details for DOI 10.1002/cnm.2523

    View details for Web of Science ID 000317311700001

    View details for PubMedID 23559551

  • An efficient framework for optimization and parameter sensitivity analysis in arterial growth and remodeling computations COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Sankaran, S., Humphrey, J. D., Marsden, A. L. 2013; 256: 200-210
  • Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge. Journal of biomechanical engineering Steinman, D. A., Hoi, Y., Fahy, P., Morris, L., Walsh, M. T., Aristokleous, N., Anayiotos, A. S., Papaharilaou, Y., Arzani, A., Shadden, S. C., Berg, P., Janiga, G., Bols, J., Segers, P., Bressloff, N. W., Cibis, M., Gijsen, F. H., Cito, S., Pallarés, J., Browne, L. D., Costelloe, J. A., Lynch, A. G., Degroote, J., Vierendeels, J., Fu, W., Qiao, A., Hodis, S., Kallmes, D. F., Kalsi, H., Long, Q., Kheyfets, V. O., Finol, E. A., Kono, K., Malek, A. M., Lauric, A., Menon, P. G., Pekkan, K., Esmaily Moghadam, M., Marsden, A. L., Oshima, M., Katagiri, K., Peiffer, V., Mohamied, Y., Sherwin, S. J., Schaller, J., Goubergrits, L., Usera, G., Mendina, M., Valen-Sendstad, K., Habets, D. F., Xiang, J., Meng, H., Yu, Y., Karniadakis, G. E., Shaffer, N., Loth, F. 2013; 135 (2): 021016-?


    Stimulated by a recent controversy regarding pressure drops predicted in a giant aneurysm with a proximal stenosis, the present study sought to assess variability in the prediction of pressures and flow by a wide variety of research groups. In phase I, lumen geometry, flow rates, and fluid properties were specified, leaving each research group to choose their solver, discretization, and solution strategies. Variability was assessed by having each group interpolate their results onto a standardized mesh and centerline. For phase II, a physical model of the geometry was constructed, from which pressure and flow rates were measured. Groups repeated their simulations using a geometry reconstructed from a micro-computed tomography (CT) scan of the physical model with the measured flow rates and fluid properties. Phase I results from 25 groups demonstrated remarkable consistency in the pressure patterns, with the majority predicting peak systolic pressure drops within 8% of each other. Aneurysm sac flow patterns were more variable with only a few groups reporting peak systolic flow instabilities owing to their use of high temporal resolutions. Variability for phase II was comparable, and the median predicted pressure drops were within a few millimeters of mercury of the measured values but only after accounting for submillimeter errors in the reconstruction of the life-sized flow model from micro-CT. In summary, pressure can be predicted with consistency by CFD across a wide range of solvers and solution strategies, but this may not hold true for specific flow patterns or derived quantities. Future challenges are needed and should focus on hemodynamic quantities thought to be of clinical interest.

    View details for DOI 10.1115/1.4023382

    View details for PubMedID 23445061

  • Predictive modeling of the virtual Hemi-Fontan operation for second stage single ventricle palliation: Two patient-specific cases JOURNAL OF BIOMECHANICS Kung, E., Baretta, A., Baker, C., Arbia, G., Biglino, G., Corsini, C., Schievano, S., Vignon-Clementel, I. E., Dubini, G., Pennati, G., Taylor, A., Dorfman, A., Hlavacek, A. M., Marsden, A. L., Hsia, T., Migliavacca, F. 2013; 46 (2): 423-429


    Single ventricle hearts are congenital cardiovascular defects in which the heart has only one functional pumping chamber. The treatment for these conditions typically requires a three-staged operative process where Stage 1 is typically achieved by a shunt between the systemic and pulmonary arteries, and Stage 2 by connecting the superior venous return to the pulmonary circulation. Surgically, the Stage 2 circulation can be achieved through a procedure called the Hemi-Fontan, which reconstructs the right atrium and pulmonary artery to allow for an enlarged confluence with the superior vena cava. Based on pre-operative data obtained from two patients prior to Stage 2 surgery, we developed two patient-specific multi-scale computational models, each including the 3D geometrical model of the surgical junction constructed from magnetic resonance imaging, and a closed-loop systemic lumped-parameter network derived from clinical measurements. "Virtual" Hemi-Fontan surgery was performed on the 3D model with guidance from clinical surgeons, and a corresponding multi-scale simulation predicts the patient's post-operative hemodynamic and physiologic conditions. For each patient, a post-operative active scenario with an increase in the heart rate (HR) and a decrease in the pulmonary and systemic vascular resistance (PVR and SVR) was also performed. Results between the baseline and this "active" state were compared to evaluate the hemodynamic and physiologic implications of changing conditions. Simulation results revealed a characteristic swirling vortex in the Hemi-Fontan in both patients, with flow hugging the wall along the SVC to Hemi-Fontan confluence. One patient model had higher levels of swirling, recirculation, and flow stagnation. However, in both models, the power loss within the surgical junction was less than 13% of the total power loss in the pulmonary circulation, and less than 2% of the total ventricular power. This implies little impact of the surgical junction geometry on the SVC pressure, cardiac output, and other systemic parameters. In contrast, varying HR, PVR, and SVR led to significant changes in theses clinically relevant global parameters. Adopting a work-flow of customized virtual planning of the Hemi-Fontan procedure with patient-specific data, this study demonstrates the ability of multi-scale modeling to reproduce patient specific flow conditions under differing physiological states. Results demonstrate that the same operation performed in two different patients can lead to different hemodynamic characteristics, and that modeling can be used to uncover physiologic changes associated with different clinical conditions.

    View details for DOI 10.1016/j.jbiomech.2012.10.023

    View details for Web of Science ID 000314794200025

    View details for PubMedID 23174419

  • Optimization of a Y-Graft Design for Improved Hepatic Flow Distribution in the Fontan Circulation JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Yang, W., Feinstein, J. A., Shadden, S. C., Vignon-Clementel, I. E., Marsden, A. L. 2013; 135 (1)


    Single ventricle heart defects are among the most serious congenital heart diseases, and are uniformly fatal if left untreated. Typically, a three-staged surgical course, consisting of the Norwood, Glenn, and Fontan surgeries is performed, after which the superior vena cava (SVC) and inferior vena cava (IVC) are directly connected to the pulmonary arteries (PA). In an attempt to improve hemodynamic performance and hepatic flow distribution (HFD) of Fontan patients, a novel Y-shaped graft has recently been proposed to replace the traditional tube-shaped extracardiac grafts. Previous studies have demonstrated that the Y-graft is a promising design with the potential to reduce energy loss and improve HFD. However these studies also found suboptimal Y-graft performance in some patient models. The goal of this work is to determine whether performance can be improved in these models through further design optimization. Geometric and hemodynamic factors that influence the HFD have not been sufficiently investigated in previous work, particularly for the Y-graft. In this work, we couple Lagrangian particle tracking to an optimal design framework to study the effects of boundary conditions and geometry on HFD. Specifically, we investigate the potential of using a Y-graft design with unequal branch diameters to improve hepatic distribution under a highly uneven RPA/LPA flow split. As expected, the resulting optimal Y-graft geometry largely depends on the pulmonary flow split for a particular patient. The unequal branch design is demonstrated to be unnecessary under most conditions, as it is possible to achieve the same or better performance with equal-sized branches. Two patient-specific examples show that optimization-derived Y-grafts effectively improve the HFD, compared to initial nonoptimized designs using equal branch diameters. An instance of constrained optimization shows that energy efficiency slightly increases with increasing branch size for the Y-graft, but that a smaller branch size is preferred when a proximal anastomosis is needed to achieve optimal HFD.

    View details for DOI 10.1115/1.4023089

    View details for Web of Science ID 000314033800002

    View details for PubMedID 23363213

  • Patient-Specific Multiscale Modeling of Blood Flow for Coronary Artery Bypass Graft Surgery ANNALS OF BIOMEDICAL ENGINEERING Sankaran, S., Moghadam, M. E., Kahn, A. M., Tseng, E. E., Guccione, J. M., Marsden, A. L. 2012; 40 (10): 2228-2242


    We present a computational framework for multiscale modeling and simulation of blood flow in coronary artery bypass graft (CABG) patients. Using this framework, only CT and non-invasive clinical measurements are required without the need to assume pressure and/or flow waveforms in the coronaries and we can capture global circulatory dynamics. We demonstrate this methodology in a case study of a patient with multiple CABGs. A patient-specific model of the blood vessels is constructed from CT image data to include the aorta, aortic branch vessels (brachiocephalic artery and carotids), the coronary arteries and multiple bypass grafts. The rest of the circulatory system is modeled using a lumped parameter network (LPN) 0 dimensional (0D) system comprised of resistances, capacitors (compliance), inductors (inertance), elastance and diodes (valves) that are tuned to match patient-specific clinical data. A finite element solver is used to compute blood flow and pressure in the 3D (3 dimensional) model, and this solver is implicitly coupled to the 0D LPN code at all inlets and outlets. By systematically parameterizing the graft geometry, we evaluate the influence of graft shape on the local hemodynamics, and global circulatory dynamics. Virtual manipulation of graft geometry is automated using Bezier splines and control points along the pathlines. Using this framework, we quantify wall shear stress, wall shear stress gradients and oscillatory shear index for different surgical geometries. We also compare pressures, flow rates and ventricular pressure-volume loops pre- and post-bypass graft surgery. We observe that PV loops do not change significantly after CABG but that both coronary perfusion and local hemodynamic parameters near the anastomosis region change substantially. Implications for future patient-specific optimization of CABG are discussed.

    View details for DOI 10.1007/s10439-012-0579-3

    View details for Web of Science ID 000308638400012

    View details for PubMedID 22539149

  • Respiratory effects on hemodynamics in patient-specific CFD models of the Fontan circulation under exercise conditions EUROPEAN JOURNAL OF MECHANICS B-FLUIDS Baretta, A., Corsini, C., Marsden, A. L., Vignon-Clementel, I. E., Hsia, T., Dubini, G., Migliavacca, F., Pennati, G. 2012; 35: 61-69
  • Image-based modeling of hemodynamics in coronary artery aneurysms caused by Kawasaki disease BIOMECHANICS AND MODELING IN MECHANOBIOLOGY Sengupta, D., Kahn, A. M., Burns, J. C., Sankaran, S., Shadden, S. C., Marsden, A. L. 2012; 11 (6): 915-932


    Kawasaki Disease (KD) is the leading cause of acquired pediatric heart disease. A subset of KD patients develops aneurysms in the coronary arteries, leading to increased risk of thrombosis and myocardial infarction. Currently, there are limited clinical data to guide the management of these patients, and the hemodynamic effects of these aneurysms are unknown. We applied patient-specific modeling to systematically quantify hemodynamics and wall shear stress in coronary arteries with aneurysms caused by KD. We modeled the hemodynamics in the aneurysms using anatomic data obtained by multi-detector computed tomography (CT) in a 10-year-old male subject who suffered KD at age 3 years. The altered hemodynamics were compared to that of a reconstructed normal coronary anatomy using our subject as the model. Computer simulations using a robust finite element framework were used to quantify time-varying shear stresses and particle trajectories in the coronary arteries. We accounted for the cardiac contractility and the microcirculation using physiologic downstream boundary conditions. The presence of aneurysms in the proximal coronary artery leads to flow recirculation, reduced wall shear stress within the aneurysm, and high wall shear stress gradients at the neck of the aneurysm. The wall shear stress in the KD subject (2.95-3.81 dynes/sq cm) was an order of magnitude lower than the normal control model (17.10-27.15 dynes/sq cm). Particle residence times were significantly higher, taking 5 cardiac cycles to fully clear from the aneurysmal regions in the KD subject compared to only 1.3 cardiac cycles from the corresponding regions of the normal model. In this novel quantitative study of hemodynamics in coronary aneurysms caused by KD, we documented markedly abnormal flow patterns that are associated with increased risk of thrombosis. This methodology has the potential to provide further insights into the effects of aneurysms in KD and to help risk stratify patients for appropriate medical and surgical interventions.

    View details for DOI 10.1007/s10237-011-0361-8

    View details for Web of Science ID 000304814100014

    View details for PubMedID 22120599

  • Identification of Hemodynamically Optimal Coronary Stent Designs Based on Vessel Caliber IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Gundert, T. J., Marsden, A. L., Yang, W., Marks, D. S., LaDisa, J. F. 2012; 59 (7): 1992-2002


    Coronary stent design influences local patterns of wall shear stress (WSS) that are associated with neointimal growth, restenosis, and the endothelialization of stent struts. The number of circumferentially repeating crowns N(C) for a given stent design is often modified depending on the target vessel caliber, but the hemodynamic implications of altering N(C) have not previously been studied. In this investigation, we analyzed the relationship between vessel diameter and the hemodynamically optimal N(C) using a derivative-free optimization algorithm coupled with computational fluid dynamics. The algorithm computed the optimal vessel diameter, defined as minimizing the area of stent-induced low WSS, for various configurations (i.e., N(C)) of a generic slotted-tube design and designs that resemble commercially available stents. Stents were modeled in idealized coronary arteries with a vessel diameter that was allowed to vary between 2 and 5 mm. The results indicate that the optimal vessel diameter increases for stent configurations with greater N(C), and the designs of current commercial stents incorporate a greater N(C) than hemodynamically optimal stent designs. This finding suggests that reducing the N(C) of current stents may improve the hemodynamic environment within stented arteries and reduce the likelihood of excessive neointimal growth and thrombus formation.

    View details for DOI 10.1109/TBME.2012.2196275

    View details for Web of Science ID 000305622100022

    View details for PubMedID 22547450

  • Rat airway morphometry measured from in situ MRI-based geometric models JOURNAL OF APPLIED PHYSIOLOGY Oakes, J. M., Scadeng, M., Breen, E. C., Marsden, A. L., Darquenne, C. 2012; 112 (11): 1921-1931


    Rodents have been widely used to study the environmental or therapeutic impact of inhaled particles. Knowledge of airway morphometry is essential in assessing geometric influence on aerosol deposition and in developing accurate lung models of aerosol transport. Previous morphometric studies of the rat lung performed ex situ provided high-resolution measurements (50-125 μm). However, it is unclear how the overall geometry of these casts might have differed from the natural in situ appearance. In this study, four male Wistar rat (268 ± 14 g) lungs were filled sequentially with perfluorocarbon and phosphate-buffered saline before being imaged in situ in a 7-T magnetic resonance (MR) scanner at a resolution of 0.2 × 0.2 × 0.27 mm. Airway length, diameter, gravitational, bifurcation, and rotational angles were measured for the first four airway generations from 3D geometric models built from the MR images. Minor interanimal variability [expressed by the relative standard deviation RSD (=SD/mean)] was found for length (0.18 ± 0.07), diameter (0.15 ± 0.15), and gravitational angle (0.12 ± 0.06). One rat model was extended to 16 airway generations. Organization of the airways using a diameter-defined Strahler ordering method resulted in lower interorder variability than conventional generation-based grouping for both diameter (RSD = 0.12 vs. 0.42) and length (0.16 vs. 0.67). Gravitational and rotational angles averaged 82.9 ± 37.9° and 53.6 ± 24.1°, respectively. Finally, the major daughter branch bifurcated at a smaller angle (19.3 ± 14.6°) than the minor branch (60.5 ± 19.4°). These data represent the most comprehensive set of rodent in situ measurements to date and can be used readily in computational studies of lung function and aerosol exposure.

    View details for DOI 10.1152/japplphysiol.00018.2012

    View details for Web of Science ID 000304810500015

    View details for PubMedID 22461437

  • Fluid-structure interaction simulations of the Fontan procedure using variable wall properties INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING Long, C. C., Hsu, M., Bazilevs, Y., Feinstein, J. A., Marsden, A. L. 2012; 28 (5): 513-527


    Children born with single ventricle heart defects typically undergo a staged surgical procedure culminating in a total cavopulmonary connection (TCPC) or Fontan surgery. The goal of this work was to perform physiologic, patient-specific hemodynamic simulations of two post-operative TCPC patients by using fluid-structure interaction (FSI) simulations. Data from two patients are presented, and post-op anatomy is reconstructed from MRI data. Respiration rate, heart rate, and venous pressures are obtained from catheterization data, and inflow rates are obtained from phase contrast MRI data and are used together with a respiratory model. Lumped parameter (Windkessel) boundary conditions are used at the outlets. We perform FSI simulations by using an arbitrary Lagrangian-Eulerian finite element framework to account for motion of the blood vessel walls in the TCPC. This study is the first to introduce variable elastic properties for the different areas of the TCPC, including a Gore-Tex conduit. Quantities such as wall shear stresses and pressures at critical locations are extracted from the simulation and are compared with pressure tracings from clinical data as well as with rigid wall simulations. Hepatic flow distribution and energy efficiency are also calculated and compared for all cases. There is little effect of FSI on pressure tracings, hepatic flow distribution, and time-averaged energy efficiency. However, the effect of FSI on wall shear stress, instantaneous energy efficiency, and wall motion is significant and should be considered in future work, particularly for accurate prediction of thrombus formation.

    View details for DOI 10.1002/cnm.1485

    View details for Web of Science ID 000303441300002

  • Optimization of Shunt Placement for the Norwood Surgery Using Multi-Domain Modeling JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Moghadam, M. E., Migliavacca, F., Vignon-Clementel, I. E., Hsia, T., Marsden, A. L. 2012; 134 (5)


    An idealized systemic-to-pulmonary shunt anatomy is parameterized and coupled to a closed loop, lumped parameter network (LPN) in a multidomain model of the Norwood surgical anatomy. The LPN approach is essential for obtaining information on global changes in cardiac output and oxygen delivery resulting from changes in local geometry and physiology. The LPN is fully coupled to a custom 3D finite element solver using a semi-implicit approach to model the heart and downstream circulation. This closed loop multidomain model is then integrated with a fully automated derivative-free optimization algorithm to obtain optimal shunt geometries with variable parameters of shunt diameter, anastomosis location, and angles. Three objective functions: (1) systemic; (2) coronary; and (3) combined systemic and coronary oxygen deliveries are maximized. Results show that a smaller shunt diameter with a distal shunt-brachiocephalic anastomosis is optimal for systemic oxygen delivery, whereas a more proximal anastomosis is optimal for coronary oxygen delivery and a shunt between these two anatomies is optimal for both systemic and coronary oxygen deliveries. Results are used to quantify the origin of blood flow going through the shunt and its relationship with shunt geometry. Results show that coronary artery flow is directly related to shunt position.

    View details for DOI 10.1115/1.4006814

    View details for Web of Science ID 000305793100002

    View details for PubMedID 22757490

  • Hepatic blood flow distribution and performance in conventional and novel Y-graft Fontan geometries: A case series computational fluid dynamics study JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, W., Vignon-Clementel, I. E., Troianowski, G., Reddy, V. M., Feinstein, J. A., Marsden, A. L. 2012; 143 (5): 1086-1097


    A novel Y-shaped baffle has been proposed for the Fontan operation with promising initial results. However, previous studies have relied either on idealized models or a single patient-specific model. The objective of this study is to comprehensively compare the hemodynamic performance and hepatic blood flow distribution of the Y-graft Fontan baffle with 2 current designs using multiple patient-specific models.Y-shaped and tube-shaped grafts were virtually implanted into 5 patient-specific Glenn models forming 3 types of Fontan geometries: Y-graft, T-junction, and offset. Unsteady flow simulations were performed at rest and at varying exercise conditions. The hepatic flow distribution between the right and left lungs was carefully quantified using a particle tracking method. Other physiologically relevant parameters such as energy dissipation, superior vena cava pressure, and wall shear stress were evaluated.The Fontan geometry significantly influences the hepatic flow distribution. The Y-graft design improves the hepatic flow distribution effectively in 4 of 5 patients, whereas the T-junction and offset designs may skew as much as 97% of hepatic flow to 1 lung in 2 cases. Sensitivity studies show that changes in pulmonary flow split can affect the hepatic flow distribution dramatically but that some Y-graft and T-junction designs are relatively less sensitive than offset designs. The Y-graft design offers moderate improvements over the traditional designs in power loss and superior vena cava pressure in all patients.The Y-graft Fontan design achieves overall superior hemodynamic performance compared with traditional designs. However, the results emphasize that no one-size-fits-all solution is available that will universally benefit all patients and that designs should be customized for individual patients before clinical application.

    View details for DOI 10.1016/j.jtcvs.2011.06.042

    View details for Web of Science ID 000302810700015

    View details for PubMedID 21962841

  • Hypoplastic Left Heart Syndrome Current Considerations and Expectations JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Feinstein, J. A., Benson, D. W., Dubin, A. M., Cohen, M. S., Maxey, D. M., Mahle, W. T., Pahl, E., Villafane, J., Bhatt, A. B., Peng, L. F., Johnson, B. A., Marsden, A. L., Daniels, C. J., Rudd, N. A., Caldarone, C. A., Mussatto, K. A., Morales, D. L., Ivy, D. D., Gaynor, J. W., Tweddell, J. S., Deal, B. J., Furck, A. K., Rosenthal, G. L., Ohye, R. G., Ghanayem, N. S., Cheatham, J. P., Tworetzky, W., Martin, G. R. 2012; 59 (1): S1-S42


    In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

    View details for DOI 10.1016/j.jacc.2011.09.022

    View details for PubMedID 22192720

  • COMPARISON OF CLINICAL AND SIMULATION RESULTS FOR THE STANFORD Y-GRAFT FONTAN PILOT TRIAL ASME Summer Bioengineering Conference (SBC) Yang, W., Feinstein, J. A., Reddy, V. M., Chan, F. P., Marsden, A. L. AMER SOC MECHANICAL ENGINEERS. 2012: 463–464
  • Optimization of Cardiovascular Stent Design Using Computational Fluid Dynamics JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Gundert, T. J., Marsden, A. L., Yang, W., LaDisa, J. F. 2012; 134 (1)


    Coronary stent design affects the spatial distribution of wall shear stress (WSS), which can influence the progression of endothelialization, neointimal hyperplasia, and restenosis. Previous computational fluid dynamics (CFD) studies have only examined a small number of possible geometries to identify stent designs that reduce alterations in near-wall hemodynamics. Based on a previously described framework for optimizing cardiovascular geometries, we developed a methodology that couples CFD and three-dimensional shape-optimization for use in stent design. The optimization procedure was fully-automated, such that solid model construction, anisotropic mesh generation, CFD simulation, and WSS quantification did not require user intervention. We applied the method to determine the optimal number of circumferentially repeating stent cells (N(C)) for slotted-tube stents with various diameters and intrastrut areas. Optimal stent designs were defined as those minimizing the area of low intrastrut time-averaged WSS. Interestingly, we determined that the optimal value of N(C) was dependent on the intrastrut angle with respect to the primary flow direction. Further investigation indicated that stent designs with an intrastrut angle of approximately 40 deg minimized the area of low time-averaged WSS regardless of vessel size or intrastrut area. Future application of this optimization method to commercially available stent designs may lead to stents with superior hemodynamic performance and the potential for improved clinical outcomes.

    View details for DOI 10.1115/1.4005542

    View details for Web of Science ID 000302582100002

    View details for PubMedID 22482657

  • Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES BARETTA, A., Corsini, C., Yang, W., Vignon-Clementel, I. E., Marsden, A. L., Feinstein, J. A., Hsia, T., Dubini, G., Migliavacca, F., Pennati, G. 2011; 369 (1954): 4316-4330


    The objective of this work is to perform a virtual planning of surgical repairs in patients with congenital heart diseases--to test the predictive capability of a closed-loop multi-scale model. As a first step, we reproduced the pre-operative state of a specific patient with a univentricular circulation and a bidirectional cavopulmonary anastomosis (BCPA), starting from the patient's clinical data. Namely, by adopting a closed-loop multi-scale approach, the boundary conditions at the inlet and outlet sections of the three-dimensional model were automatically calculated by a lumped parameter network. Successively, we simulated three alternative surgical designs of the total cavopulmonary connection (TCPC). In particular, a T-junction of the venae cavae to the pulmonary arteries (T-TCPC), a design with an offset between the venae cavae (O-TCPC) and a Y-graft design (Y-TCPC) were compared. A multi-scale closed-loop model consisting of a lumped parameter network representing the whole circulation and a patient-specific three-dimensional finite volume model of the BCPA with detailed pulmonary anatomy was built. The three TCPC alternatives were investigated in terms of energetics and haemodynamics. Effects of exercise were also investigated. Results showed that the pre-operative caval flows should not be used as boundary conditions in post-operative simulations owing to changes in the flow waveforms post-operatively. The multi-scale approach is a possible solution to overcome this incongruence. Power losses of the Y-TCPC were lower than all other TCPC models both at rest and under exercise conditions and it distributed the inferior vena cava flow evenly to both lungs. Further work is needed to correlate results from these simulations with clinical outcomes.

    View details for DOI 10.1098/rsta.2011.0130

    View details for Web of Science ID 000295458900010

    View details for PubMedID 21969678

  • A comparison of outlet boundary treatments for prevention of backflow divergence with relevance to blood flow simulations COMPUTATIONAL MECHANICS Moghadam, M. E., Bazilevs, Y., Hsia, T., Vignon-Clementel, I. E., Marsden, A. L. 2011; 48 (3): 277-291
  • Towards inverse modeling of turbidity currents: The inverse lock-exchange problem COMPUTERS & GEOSCIENCES Lesshafft, L., Meiburg, E., Kneller, B., Marsden, A. 2011; 37 (4): 521-529
  • A Stochastic Collocation Method for Uncertainty Quantification and Propagation in Cardiovascular Simulations JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Sankaran, S., Marsden, A. L. 2011; 133 (3)


    Simulations of blood flow in both healthy and diseased vascular models can be used to compute a range of hemodynamic parameters including velocities, time varying wall shear stress, pressure drops, and energy losses. The confidence in the data output from cardiovascular simulations depends directly on our level of certainty in simulation input parameters. In this work, we develop a general set of tools to evaluate the sensitivity of output parameters to input uncertainties in cardiovascular simulations. Uncertainties can arise from boundary conditions, geometrical parameters, or clinical data. These uncertainties result in a range of possible outputs which are quantified using probability density functions (PDFs). The objective is to systemically model the input uncertainties and quantify the confidence in the output of hemodynamic simulations. Input uncertainties are quantified and mapped to the stochastic space using the stochastic collocation technique. We develop an adaptive collocation algorithm for Gauss-Lobatto-Chebyshev grid points that significantly reduces computational cost. This analysis is performed on two idealized problems--an abdominal aortic aneurysm and a carotid artery bifurcation, and one patient specific problem--a Fontan procedure for congenital heart defects. In each case, relevant hemodynamic features are extracted and their uncertainty is quantified. Uncertainty quantification of the hemodynamic simulations is done using (a) stochastic space representations, (b) PDFs, and (c) the confidence intervals for a specified level of confidence in each problem.

    View details for DOI 10.1115/1.4003259

    View details for Web of Science ID 000287096100001

    View details for PubMedID 21303177

  • Imaging and patient-specific simulations for the Fontan surgery: current methodologies and clinical applications. Progress in pediatric cardiology de Zélicourt, D. A., Marsden, A., Fogel, M. A., Yoganathan, A. P. 2010; 30 (1-2): 31-44

    View details for PubMedID 25620865

  • The impact of uncertainty on shape optimization of idealized bypass graft models in unsteady flow PHYSICS OF FLUIDS Sankaran, S., Marsden, A. L. 2010; 22 (12)

    View details for DOI 10.1063/1.3529444

    View details for Web of Science ID 000285770200005

  • A method for stochastic constrained optimization using derivative-free surrogate pattern search and collocation JOURNAL OF COMPUTATIONAL PHYSICS Sankaran, S., Audet, C., Marsden, A. L. 2010; 229 (12): 4664-4682
  • A New Multiparameter Approach to Computational Simulation for Fontan Assessment and Redesign CONGENITAL HEART DISEASE Marsden, A. L., Reddy, V. M., Shadden, S. C., Chan, F. P., Taylor, C. A., Feinstein, J. A. 2010; 5 (2): 104-117


    Despite an abundance of prior Fontan simulation articles, there have been relatively few clinical advances that are a direct result of computational methods. We address a few key limitations of previous Fontan simulations as a step towards increasing clinical relevance. Previous simulations have been limited in scope because they have primarily focused on a single energy loss parameter. We present a multi-parameter approach to Fontan modeling that establishes a platform for clinical decision making and comprehensive evaluation of proposed interventions.Time-dependent, 3-D blood flow simulations were performed on six patient-specific Fontan models. Key modeling advances include detailed pulmonary anatomy, catheterization-derived pressures, and MRI-derived flow with respiration. The following performance parameters were used to rank patients at rest and simulated exercise from best to worst performing: energy efficiency, inferior and superior vena cava (IVC, SVC) pressures, wall shear stress, and IVC flow distribution.Simulated pressures were well matched to catheterization data, but low Fontan pressure did not correlate with high efficiency. Efficiency varied from 74% to 96% at rest, and from 63% to 91% with exercise. Distribution of IVC flow ranged from 88%/12% (LPA/RPA) to 53%/47%. A "transcatheter" virtual intervention demonstrates the utility of computation in evaluating interventional strategies, and is shown to result in increased energy efficiency.A multiparameter approach demonstrates that each parameter results in a different ranking of Fontan performance. Ranking patients using energy efficiency does not correlate with the ranking using other parameters of presumed clinical importance. As such, current simulation methods that evaluate energy dissipation alone are not sufficient for a comprehensive evaluation of new Fontan designs.

    View details for DOI 10.1111/j.1747-0803.2010.00383.x

    View details for Web of Science ID 000289417500004

    View details for PubMedID 20412482

  • Constrained optimization of an idealized Y-shaped baffle for the Fontan surgery at rest and exercise COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Yang, W., Feinstein, J. A., Marsden, A. L. 2010; 199 (33-36): 2135-2149
  • Computational fluid-structure interaction: methods and application to a total cavopulmonary connection COMPUTATIONAL MECHANICS Bazilevs, Y., Hsu, M., Benson, D. J., Sankaran, S., Marsden, A. L. 2009; 45 (1): 77-89
  • Evaluation of a novel Y-shaped extracardiac Fontan baffle using computational fluid dynamics JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Marsden, A. L., Bernstein, A. J., Reddy, V. M., Shadden, S. C., Spilker, R. L., Chan, F. P., Taylor, C. A., Feinstein, J. A. 2009; 137 (2): 394-U187


    The objective of this work is to evaluate the hemodynamic performance of a new Y-graft modification of the extracardiac conduit Fontan operation. The performance of the Y-graft design is compared to two designs used in current practice: a t-junction connection of the venae cavae and an offset between the inferior and superior venae cavae.The proposed design replaces the current tube grafts used to connect the inferior vena cava to the pulmonary arteries with a Y-shaped graft. Y-graft hemodynamics were evaluated at rest and during exercise with a patient-specific model from magnetic resonance imaging data together with computational fluid dynamics. Four clinically motivated performance measures were examined: Fontan pressures, energy efficiency, inferior vena cava flow distribution, and wall shear stress. Two variants of the Y-graft were evaluated: an "off-the-shelf" graft with 9-mm branches and an "area-preserving" graft with 12-mm branches.Energy efficiency of the 12-mm Y-graft was higher than all other models at rest and during exercise, and the reduction in efficiency from rest to exercise was improved by 38%. Both Y-graft designs reduced superior vena cava pressures during exercise by as much as 5 mm Hg. The Y-graft more equally distributed the inferior vena cava flow to both lungs, whereas the offset design skewed 70% of the flow to the left lung. The 12-mm graft resulted in slightly larger regions of low wall shear stress than other models; however, minimum shear stress values were similar.The area-preserving 12-mm Y-graft is a promising modification of the Fontan procedure that should be clinically evaluated. Further work is needed to correlate our performance metrics with clinical outcomes, including exercise intolerance, incidence of protein-losing enteropathy, and thrombus formation.

    View details for DOI 10.1016/j.jtcvs.2008.06.043

    View details for Web of Science ID 000262919000020

    View details for PubMedID 19185159

  • Generation of optimal artificial neural networks using a pattern search algorithm: Application to approximation of chemical systems NEURAL COMPUTATION Ihme, M., Marsden, A. L., Pitsch, H. 2008; 20 (2): 573-601


    A pattern search optimization method is applied to the generation of optimal artificial neural networks (ANNs). Optimization is performed using a mixed variable extension to the generalized pattern search method. This method offers the advantage that categorical variables, such as neural transfer functions and nodal connectivities, can be used as parameters in optimization. When used together with a surrogate, the resulting algorithm is highly efficient for expensive objective functions. Results demonstrate the effectiveness of this method in optimizing an ANN for the number of neurons, the type of transfer function, and the connectivity among neurons. The optimization method is applied to a chemistry approximation of practical relevance. In this application, temperature and a chemical source term are approximated as functions of two independent parameters using optimal ANNs. Comparison of the performance of optimal ANNs with conventional tabulation methods demonstrates equivalent accuracy by considerable savings in memory storage. The architecture of the optimal ANN for the approximation of the chemical source term consists of a fully connected feedforward network having four nonlinear hidden layers and 117 synaptic weights. An equivalent representation of the chemical source term using tabulation techniques would require a 500 x 500 grid point discretization of the parameter space.

    View details for PubMedID 18045024

  • A computational framework for derivative-free optimization of cardiovascular geometries COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING Marsden, A. L., Feinstein, J. A., Taylor, C. A. 2008; 197 (21-24): 1890-1905
  • Large differences in efficiency among Fontan patients demonstrated in patient specific models of blood flow simulations 80th Annual Scientific Session of the American-Heart-Association (AHA) Marsden, A. L., Bernstein, A. J., Spilker, R. L., Chan, F. P., Taylor, C. A., Feinstein, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2007: 480–80
  • Trailing-edge noise reduction using derivative-free optimization and large-eddy simulation JOURNAL OF FLUID MECHANICS Marsden, A. L., Wang, M., Dennis, J. E., Moin, P. 2007; 572: 13-36
  • Effects of exercise and respiration on hemodynamic efficiency in CFD simulations of the total cavopulmonary connection ANNALS OF BIOMEDICAL ENGINEERING Marsden, A. L., Vignon-Clementel, I. E., Chan, F. P., Feinstein, J. A., Taylor, C. A. 2007; 35 (2): 250-263


    Congenital heart defects with a single functional ventricle, such as hypoplastic left heart syndrome and tricuspid atresia, require a staged surgical approach to separate the systemic and pulmonary circulations. Ultimately, the venous or pulmonary side of the heart is bypassed by directly connecting the vena cava to the pulmonary arteries with a modified t-shaped junction. The Fontan procedure (total cavopulmonary connection, TCPC) completes this process of separation. To date, computational fluid dynamics (CFD) simulations in this low pressure, passive flow, intrathoracic system have neglected the presumed important effects of respiration on physiology and higher "stress" states such as with exercise have never been considered. We hypothesize that incorporating effects of respiration and exercise would provide more realistic estimates of TCPC performance. Time-dependent, 3D blood flow simulations are performed by a custom finite element solver for two patient-specific Fontan models with a novel respiration model, developed to generate physiologic time-varying flow conditions. Blood flow features, pressure, and energy efficiency are analyzed at rest and with increasing flow rates to simulate exercise conditions. The simulations produce realistic pressure and flow data, comparable to that measured by catheterization and echocardiography, and demonstrate substantial increases in energy dissipation (i.e. decreased performance) with exercise and respiration due to increasing intensity of small scale vortices in the flow. As would be expected, these changes are highly dependent on patient-specific anatomy and Fontan geometry. We propose that respiration and exercise should be incorporated into TCPC CFD simulations to provide increasingly realistic evaluations of TCPC performance.

    View details for DOI 10.1007/s10439-006-9224-3

    View details for PubMedID 17171509

  • Evaluation of hemodynamic efficiency in a new "Y-graft" design for the Fontan operation ASME Summer Bioengineering Conference Bernstein, A. J., Marsden, A. L., Spilker, R. L., Reddy, V. M., Taylor, C. A., Feinstein, J. A. AMER SOC MECHANICAL ENGINEERS. 2007: 473–474
  • Suppression of vortex-shedding noise via derivative-free shape optimization PHYSICS OF FLUIDS Marsden, A. L., Wang, M., Dennis, J. E., Moin, P. 2004; 16 (10): L83-L86

    View details for DOI 10.1063/1.1786551

    View details for Web of Science ID 000223822300001

  • Optimal aeroacoustic shape design using the surrogate management framework OPTIMIZATION AND ENGINEERING Marsden, A. L., Wang, M., Dennis, J. E., Moin, P. 2004; 5 (2): 235-262
  • Construction of commutative filters for LES on unstructured meshes JOURNAL OF COMPUTATIONAL PHYSICS Marsden, A. L., Vasilyev, O. V., Moin, P. 2002; 175 (2): 584-603