Publications by authors named "Alessandro Veneziani"

40 Publications

Fluid-Structure Interaction Simulation of an Intra-Atrial Fontan Connection.

Biology (Basel) 2020 Nov 24;9(12). Epub 2020 Nov 24.

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

Total cavopulmonary connection (TCPC) hemodynamics has been hypothesized to be associated with long-term complications in single ventricle heart defect patients. Rigid wall assumption has been commonly used when evaluating TCPC hemodynamics using computational fluid dynamics (CFD) simulation. Previous study has evaluated impact of wall compliance on extra-cardiac TCPC hemodynamics using fluid-structure interaction (FSI) simulation. However, the impact of ignoring wall compliance on the presumably more compliant intra-atrial TCPC hemodynamics is not fully understood. To narrow this knowledge gap, this study aims to investigate impact of wall compliance on an intra-atrial TCPC hemodynamics. A patient-specific model of an intra-atrial TCPC is simulated with an FSI model. Patient-specific 3D TCPC anatomies were reconstructed from transverse cardiovascular magnetic resonance images. Patient-specific vessel flow rate from phase-contrast magnetic resonance imaging (MRI) at the Fontan pathway and the superior vena cava under resting condition were prescribed at the inlets. From the FSI simulation, the degree of wall deformation was compared with in vivo wall deformation from phase-contrast MRI data as validation of the FSI model. Then, TCPC flow structure, power loss and hepatic flow distribution (HFD) were compared between rigid wall and FSI simulation. There were differences in instantaneous pressure drop, power loss and HFD between rigid wall and FSI simulations, but no difference in the time-averaged quantities. The findings of this study support the use of a rigid wall assumption on evaluation of time-averaged intra-atrial TCPC hemodynamic metric under resting breath-held condition.
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http://dx.doi.org/10.3390/biology9120412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760396PMC
November 2020

Global Sensitivity Analysis for Patient-Specific Aortic Simulations: the Role of Geometry, Boundary Condition and LES Modeling Parameters.

J Biomech Eng 2020 Sep 3. Epub 2020 Sep 3.

Department of Mathematics, Department of Computer Science, Emory University, Atlanta, Georgia, 30322, United States.

Uncertainties affect the reliability of the numerical simulation of hemodynamics in patient-specific settings and rigorous Uncertainty Quantification (UQ) is in order. This work presents a UQ study on the aorta flow, for assessing the sensitivity of the clinical relevant quantities to the morphology and imprecise knowledge of the inflow boundary condition using the Polynomial Chaos Expansion based Sobol' indices. The geometrical uncertainty is modeled based on a set of longitudinal imaging data of a patient with the abdominal aortic aneurysm. The images of the patient's aorta at different stages of the disease are used to create a map that drives the realistic variation of the reconstructed morphology. The aorta is a peculiar site for hemodynamics, since the flow is highly disturbed due to the high Reynolds number during systole, and the modeling of turbulence helps to avoid the high computational costs. The deconvolution-based Leray model was considered in the past for these simulations. The LES model features problem-dependent numerical parameters to tune. We borrow the same UQ tools used for physical uncertain quantities to assess the sensitivity of the simulations to one of these numerical parameters, the filter radius. The sensitivity of the total kinetic energy, the time average wall shear stress, and the oscillatory shear index are analyzed. The results show that the geometry has the most dominant contribution to the uncertainty of all the quantities of interest. The sensitivity analysis provides confidence intervals for the simulations that quantify the reliability of the numerical predictions.
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http://dx.doi.org/10.1115/1.4048336DOI Listing
September 2020

Diffusion-reaction compartmental models formulated in a continuum mechanics framework: application to COVID-19, mathematical analysis, and numerical study.

Comput Mech 2020 Aug 13:1-22. Epub 2020 Aug 13.

Dipartimento di Ingegneria Civile ed Architettura, Università di Pavia, Via Ferrata 3, 27100 Pavia, PV Italy.

The outbreak of COVID-19 in 2020 has led to a surge in interest in the research of the mathematical modeling of epidemics. Many of the introduced models are so-called , in which the total quantities characterizing a certain system may be decomposed into two (or more) species that are distributed into two (or more) homogeneous units called compartments. We propose herein a formulation of compartmental models based on partial differential equations (PDEs) based on concepts familiar to continuum mechanics, interpreting such models in terms of fundamental equations of balance and compatibility, joined by a constitutive relation. We believe that such an interpretation may be useful to aid understanding and interdisciplinary collaboration. We then proceed to focus on a compartmental PDE model of COVID-19 within the newly-introduced framework, beginning with a detailed derivation and explanation. We then analyze the model mathematically, presenting several results concerning its stability and sensitivity to different parameters. We conclude with a series of numerical simulations to support our findings.
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http://dx.doi.org/10.1007/s00466-020-01888-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426072PMC
August 2020

Simulating the spread of COVID-19 a spatially-resolved susceptible-exposed-infected-recovered-deceased (SEIRD) model with heterogeneous diffusion.

Appl Math Lett 2021 Jan 15;111:106617. Epub 2020 Jul 15.

Department of Mathematics, Emory University, 400 Dowman Drive, Atlanta, GA 30322, USA.

We present an early version of a Susceptible-Exposed-Infected-Recovered-Deceased (SEIRD) mathematical model based on partial differential equations coupled with a heterogeneous diffusion model. The model describes the spatio-temporal spread of the COVID-19 pandemic, and aims to capture dynamics also based on human habits and geographical features. To test the model, we compare the outputs generated by a finite-element solver with measured data over the Italian region of Lombardy, which has been heavily impacted by this crisis between February and April 2020. Our results show a strong qualitative agreement between the simulated forecast of the spatio-temporal COVID-19 spread in Lombardy and epidemiological data collected at the municipality level. Additional simulations exploring alternative scenarios for the relaxation of lockdown restrictions suggest that reopening strategies should account for local population densities and the specific dynamics of the contagion. Thus, we argue that data-driven simulations of our model could ultimately inform health authorities to design effective pandemic-arresting measures and anticipate the geographical allocation of crucial medical resources.
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http://dx.doi.org/10.1016/j.aml.2020.106617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361091PMC
January 2021

Non-Newtonian Effects on Patient-Specific Modeling of Fontan Hemodynamics.

Ann Biomed Eng 2020 Aug 5;48(8):2204-2217. Epub 2020 May 5.

Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, GA, 30332, USA.

The Fontan procedure is a common palliative surgery for congenital single ventricle patients. In silico and in vitro patient-specific modeling approaches are widely utilized to investigate potential improvements of Fontan hemodynamics that are related to long-term complications. However, there is a lack of consensus regarding the use of non-Newtonian rheology, warranting a systematic investigation. This study conducted in silico patient-specific modeling for twelve Fontan patients, using a Newtonian and a non-Newtonian model for each patient. Differences were quantified by examining clinically relevant metrics: indexed power loss (iPL), indexed viscous dissipation rate (iVDR), hepatic flow distribution (HFD), and regions of low wall shear stress (A). Four sets of "non-Newtonian importance factors" were calculated to explore their effectiveness in identifying the non-Newtonian effect. No statistical differences were observed in iPL, iVDR, and HFD between the two models at the population-level, but large inter-patient variations exist. Significant differences were detected regarding A, and its correlations with non-Newtonian importance factors were discussed. Additionally, simulations using the non-Newtonian model were computationally faster than those using the Newtonian model. These findings distinguish good importance factors for identifying non-Newtonian rheology and encourage the use of a non-Newtonian model to assess Fontan hemodynamics.
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http://dx.doi.org/10.1007/s10439-020-02527-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415616PMC
August 2020

Analysis of Inlet Velocity Profiles in Numerical Assessment of Fontan Hemodynamics.

Ann Biomed Eng 2019 Nov 24;47(11):2258-2270. Epub 2019 Jun 24.

Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, 387 Technology Circle, Suite 232, Atlanta, GA, 30313-2412, USA.

Computational fluid dynamic (CFD) simulations are widely utilized to assess Fontan hemodynamics that are related to long-term complications. No previous studies have systemically investigated the effects of using different inlet velocity profiles in Fontan simulations. This study implements real, patient-specific velocity profiles for numerical assessment of Fontan hemodynamics using CFD simulations. Four additional, artificial velocity profiles were used for comparison: (1) flat, (2) parabolic, (3) Womersley, and (4) parabolic with inlet extensions [to develop flow before entering the total cavopulmonary connection (TCPC)]. The differences arising from the five velocity profiles, as well as discrepancies between the real and each of the artificial velocity profiles, were quantified by examining clinically important metrics in TCPC hemodynamics: power loss (PL), viscous dissipation rate (VDR), hepatic flow distribution, and regions of low wall shear stress. Statistically significant differences were observed in PL and VDR between simulations using real and flat velocity profiles, but differences between those using real velocity profiles and the other three artificial profiles did not reach statistical significance. These conclusions suggest that the artificial velocity profiles (2)-(4) are acceptable surrogates for real velocity profiles in Fontan simulations, but parabolic profiles are recommended because of their low computational demands and prevalent applicability.
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http://dx.doi.org/10.1007/s10439-019-02307-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842101PMC
November 2019

The effect of respiration-driven flow waveforms on hemodynamic metrics used in Fontan surgical planning.

J Biomech 2019 01 25;82:87-95. Epub 2018 Oct 25.

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, USA. Electronic address:

Objective: Poor total cavopulmonary connection (TCPC) hemodynamics have been hypothesized to be associated with long-term complications in Fontan patients. Image-based Fontan surgical planning has shown great potential as a clinical tool because it can pre-operatively evaluate patient-specific hemodynamics. Current surgical planning paradigms commonly utilize cardiac-gated phase contrast magnetic resonance (MR) imaging to acquire vessel flows. These acquisitions are often taken under breath-held (BH) conditions and ignore the effect of respiration on blood flow waveforms. This study investigates the effect of respiration-driven flow waveforms on patient-specific hemodynamics using real-time MR acquisitions.

Methods: Patient-specific TCPCs were reconstructed from cardiovascular MR images. Real-time phase contrast MR images were acquired under both free-breathing (FB) and breath-held conditions for 9 patients. Numerical simulations were employed to assess flow structures and hemodynamics used in Fontan surgical planning including hepatic flow distribution (HFD) and indexed power loss (iPL), which were then compared between FB and BH conditions.

Results: Differences in TCPC flow structures between FB and BH conditions were observed throughout the respiratory cycle. However, the average differences (BH - FB values for each patient, which are then averaged) in iPL and HFD between these conditions were 0.002 ± 0.011 (p = 0.40) and 1 ± 3% (p = 0.28), respectively, indicating no significant difference in clinically important hemodynamic metrics.

Conclusions: Respiration affects blood flow waveforms and flow structures, but might not significantly influence the values of iPL or HFD. Therefore, breath-held MR acquisition can be adequate for Fontan surgical planning when focusing on iPL and HFD.
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http://dx.doi.org/10.1016/j.jbiomech.2018.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310625PMC
January 2019

High Coronary Shear Stress in Patients With Coronary Artery Disease Predicts Myocardial Infarction.

J Am Coll Cardiol 2018 10;72(16):1926-1935

Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Background: Coronary lesions with low fractional flow reserve (FFR) that are treated medically are associated with higher revascularization rates. High wall shear stress (WSS) has been linked with increased plaque vulnerability.

Objectives: This study investigated the prognostic value of WSS measured in the proximal segments of lesions (WSS) to predict myocardial infarction (MI) in patients with stable coronary artery disease (CAD) and hemodynamically significant lesions. The authors hypothesized that in patients with low FFR and stable CAD, higher WSS would predict MI.

Methods: Among 441 patients in the FAME II (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation II) trial with FFR ≤0.80 who were randomized to medical therapy alone, 34 (8%) had subsequent MI within 3 years. Patients with vessel-related MI and adequate angiograms for 3-dimensional reconstruction (n = 29) were propensity matched to a control group with no MI (n = 29) by using demographic and clinical variables. Coronary lesions were divided into proximal, middle, and distal, along with 5-mm upstream and downstream segments. WSS was calculated for each segment.

Results: Median age was 62 years, and 46 (79%) were male. In the marginal Cox model, whereas lower FFR showed a trend (hazard ratio: 0.084; p = 0.064), higher WSS (hazard ratio: 1.234; p = 0.002, C-index = 0.65) predicted MI. Adding WSS to FFR resulted in a significant increase in global chi-square for predicting MI (p = 0.045), a net reclassification improvement of 0.69 (p = 0.005), and an integrated discrimination index of 0.11 (p = 0.010).

Conclusions: In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR.
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http://dx.doi.org/10.1016/j.jacc.2018.07.075DOI Listing
October 2018

Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

JACC Cardiovasc Interv 2018 10 26;11(20):2072-2080. Epub 2018 Sep 26.

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Objectives: This study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx).

Background: Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD).

Methods: Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and endothelial function testing. Segments with >10% vasoconstriction after acetylcholine (Ach) infusion were defined as having severe EDFx. WSS, calculated using 3-dimensional angiography, velocity measurements, and computational fluid dynamics, was defined as low (<1 Pa), intermediate (1 to 2.5 Pa), or high (>2.5 Pa).

Results: Median age was 52 years, 73% were women. Mean fractional flow reserve was 0.94 ± 0.06. In 4,510 coronary segments, median WSS was 3.67 Pa. A total of 24% had severe EDFx. A higher proportion of segments with low WSS had severe EDFx (71%) compared with intermediate WSS (22%) or high WSS (23%) (p < 0.001). Segments with low WSS demonstrated greater vasoconstriction in response to Ach than did intermediate or high WSS segments (-10.7% vs. -2.5% vs. +1.3%, respectively; p < 0.001). In a multivariable logistic regression analysis, female sex (odds ratio [OR]: 2.44; p = 0.04), diabetes (OR: 5.01; p = 0.007), and low WSS (OR: 9.14; p < 0.001) were independent predictors of severe EDFx.

Conclusions: In patients with nonobstructive CAD, segments with low WSS demonstrated more vasoconstriction in response to Ach than did intermediate or high WSS segments. Low WSS was independently associated with severe EDFx.
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http://dx.doi.org/10.1016/j.jcin.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217963PMC
October 2018

Patient-specific CFD modelling in the thoracic aorta with PC-MRI-based boundary conditions: A least-square three-element Windkessel approach.

Int J Numer Method Biomed Eng 2018 11 30;34(11):e3134. Epub 2018 Aug 30.

Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.

The increasing use of computational fluid dynamics for simulating blood flow in clinics demands the identification of appropriate patient-specific boundary conditions for the customization of the mathematical models. These conditions should ideally be retrieved from measurements. However, finite resolution of devices as well as other practical/ethical reasons prevent the construction of complete data sets necessary to make the mathematical problems well posed. Available data need to be completed by modelling assumptions, whose impact on the final solution has to be carefully addressed. Focusing on aortic vascular districts and related pathologies, we present here a method for efficiently and robustly prescribing phase contrast MRI-based patient-specific data as boundary conditions at the domain of interest. In particular, for the outlets, the basic idea is to obtain pressure conditions from an appropriate elaboration of available flow rates on the basis of a 3D/0D dimensionally heterogeneous modelling. The key point is that the parameters are obtained by a constrained optimization procedure. The rationale is that pressure conditions have a reduced impact on the numerical solution compared with velocity conditions, yielding a simulation framework less exposed to noise and inconsistency of the data, as well as to the arbitrariness of the underlying modelling assumptions. Numerical results confirm the reliability of the approach in comparison with other patient-specific approaches adopted in the literature.
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http://dx.doi.org/10.1002/cnm.3134DOI Listing
November 2018

Coupled Morphological-Hemodynamic Computational Analysis of Type B Aortic Dissection: A Longitudinal Study.

Ann Biomed Eng 2018 Jul 28;46(7):927-939. Epub 2018 Mar 28.

Department of Mathematics and Computer Science, Emory University, Atlanta, USA.

Progressive false lumen aneurysmal degeneration in type B aortic dissection (TBAD) is a complex process with a multi-factorial etiology. Patient-specific computational fluid dynamics (CFD) simulations provide spatial and temporal hemodynamic quantities that facilitate understanding this disease progression. A longitudinal study was performed for a TBAD patient, who was diagnosed with the uncomplicated TBAD in 2006 and treated with optimal medical therapy but received surgery in 2010 due to late complication. Geometries of the aorta in 2006 and 2010 were reconstructed. With registration algorithms, we accurately quantified the evolution of the false lumen, while with CFD simulations we computed several hemodynamic indexes, including the wall shear stress (WSS), and the relative residence time (RRT). The numerical fluid model included large eddy simulation (LES) modeling for efficiently capturing the flow disturbances induced by the entry tears. In the absence of complete patient-specific data, the boundary conditions were based on a specific calibration method. Correlations between hemodynamics and the evolution field in time obtained by registration of the false lumen are discussed. Further testing of this methodology on a large cohort of patients may enable the use of CFD to predict whether patients, with originally uncomplicated TBAD, develop late complications.
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http://dx.doi.org/10.1007/s10439-018-2012-zDOI Listing
July 2018

Numerical methods for polyline-to-point-cloud registration with applications to patient-specific stent reconstruction.

Int J Numer Method Biomed Eng 2018 03 29;34(3). Epub 2017 Nov 29.

Department of Mathematics and Computer Science, Emory University, 400 Dowman Dr NE, Atlanta, 30322, GA, USA.

We present novel numerical methods for polyline-to-point-cloud registration and their application to patient-specific modeling of deployed coronary artery stents from image data. Patient-specific coronary stent reconstruction is an important challenge in computational hemodynamics and relevant to the design and improvement of the prostheses. It is an invaluable tool in large-scale clinical trials that computationally investigate the effect of new generations of stents on hemodynamics and eventually tissue remodeling. Given a point cloud of strut positions, which can be extracted from images, our stent reconstruction method aims at finding a geometrical transformation that aligns a model of the undeployed stent to the point cloud. Mathematically, we describe the undeployed stent as a polyline, which is a piecewise linear object defined by its vertices and edges. We formulate the nonlinear registration as an optimization problem whose objective function consists of a similarity measure, quantifying the distance between the polyline and the point cloud, and a regularization functional, penalizing undesired transformations. Using projections of points onto the polyline structure, we derive novel distance measures. Our formulation supports most commonly used transformation models including very flexible nonlinear deformations. We also propose 2 regularization approaches ensuring the smoothness of the estimated nonlinear transformation. We demonstrate the potential of our methods using an academic 2D example and a real-life 3D bioabsorbable stent reconstruction problem. Our results show that the registration problem can be solved to sufficient accuracy within seconds using only a few number of Gauss-Newton iterations.
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http://dx.doi.org/10.1002/cnm.2934DOI Listing
March 2018

Numerical sensitivity analysis of a variational data assimilation procedure for cardiac conductivities.

Chaos 2017 Sep;27(9):093930

Department of Mathematics and Computer Science, Emory University, Atlanta, Georgia, USA; School of Advanced Studies IUSS, Pavia, Italy.

An accurate estimation of cardiac conductivities is critical in computational electro-cardiology, yet experimental results in the literature significantly disagree on the values and ratios between longitudinal and tangential coefficients. These are known to have a strong impact on the propagation of potential particularly during defibrillation shocks. Data assimilation is a procedure for merging experimental data and numerical simulations in a rigorous way. In particular, variational data assimilation relies on the least-square minimization of the misfit between simulations and experiments, constrained by the underlying mathematical model, which in this study is represented by the classical Bidomain system, or its common simplification given by the Monodomain problem. Operating on the conductivity tensors as control variables of the minimization, we obtain a parameter estimation procedure. As the theory of this approach currently provides only an existence proof and it is not informative for practical experiments, we present here an extensive numerical simulation campaign to assess practical critical issues such as the size and the location of the measurement sites needed for in silico test cases of potential experimental and realistic settings. This will be finalized with a real validation of the variational data assimilation procedure. Results indicate the presence of lower and upper bounds for the number of sites which guarantee an accurate and minimally redundant parameter estimation, the location of sites being generally non critical for properly designed experiments. An effective combination of parameter estimation based on the Monodomain and Bidomain models is tested for the sake of computational efficiency. Parameter estimation based on the Monodomain equation potentially leads to the accurate computation of the transmembrane potential in real settings.
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http://dx.doi.org/10.1063/1.5001454DOI Listing
September 2017

SEX AND VASCULAR BIOMECHANICS: A HYPOTHESIS FOR THE MECHANISM UNDERLYING DIFFERENCES IN THE PREVALENCE OF ABDOMINAL AORTIC ANEURYSMS IN MEN AND WOMEN.

Trans Am Clin Climatol Assoc 2016 ;127:148-161

ATLANTA, GEORGIA.

The prevalence of abdominal aortic aneurysms differs greatly between men and women across the spectrum of ages. The reason for this discrepancy is not clear and likely involves several factors including the impact of sex hormones. We hypothesize that the unique spatial localization of abdominal aortic aneurysms is dictated in part by local hemodynamic forces on the vascular wall. Specifically, we propose that oscillatory shear stress is a specific signal to the endothelium that initiates the events ultimately leading to abdominal aortic aneurysm formation. We are proposing that sex-dependent differences in oscillatory shear stress in the infra-renal aorta may explain the observed differences between men and women. Initial observations suggest that, indeed, men and women have different degrees of oscillatory blood flow in the infra-renal abdominal aorta. The challenge is to extend these observations to show a causal relationship between oscillatory flow and aneurysm formation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216511PMC
March 2018

Transversally enriched pipe element method (TEPEM): An effective numerical approach for blood flow modeling.

Int J Numer Method Biomed Eng 2017 04 27;33(4). Epub 2016 Jul 27.

National Laboratory for Scientific Computing, LNCC/MCTI, Av. Getúlio Vargas 333, 25651-075, Petrópolis, Brazil.

In this work, we present a novel approach tailored to approximate the Navier-Stokes equations to simulate fluid flow in three-dimensional tubular domains of arbitrary cross-sectional shape. The proposed methodology is aimed at filling the gap between (cheap) one-dimensional and (expensive) three-dimensional models, featuring descriptive capabilities comparable with the full and accurate 3D description of the problem at a low computational cost. In addition, this methodology can easily be tuned or even adapted to address local features demanding more accuracy. The numerical strategy employs finite (pipe-type) elements that take advantage of the pipe structure of the spatial domain under analysis. While low order approximation is used for the longitudinal description of the physical fields, transverse approximation is enriched using high order polynomials. Although our application of interest is computational hemodynamics and its relevance to pathological dynamics like atherosclerosis, the approach is quite general and can be applied in any internal fluid dynamics problem in pipe-like domains. Numerical examples covering academic cases as well as patient-specific coronary arterial geometries demonstrate the potentialities of the developed methodology and its performance when compared against traditional finite element methods. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/cnm.2808DOI Listing
April 2017

Feasibility of Optical Coherence Tomography-Derived Computational Fluid Dynamics in Calcified Vessels to Assess Treatment With Orbital Atherectomy.

JACC Cardiovasc Interv 2016 Apr;9(7):e65-6

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Emory Cardiovascular Imaging & Biomechanics Core Laboratory, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2015.12.270DOI Listing
April 2016

Vasomotor Function Comparative Assessment at 1 and 2 Years Following Implantation of the Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold and the Xience V Everolimus-Eluting Metallic Stent in Porcine Coronary Arteries: Insights From In Vivo Angiography, Ex Vivo Assessment, and Gene Analysis at the Stented/Scaffolded Segments and the Proximal and Distal Edges.

JACC Cardiovasc Interv 2016 Apr;9(7):728-41

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Emory Cardiovascular Imaging & Biomechanics Core Laboratory, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Objectives: The purpose of this study was to assess and compare in vivo the restoration of vasomotor function following Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and metallic Xience V (XV) (Abbott Vascular, Santa Clara, California) stent implantations in porcine coronary arteries at 1 and 2 years.

Background: Drug-eluting metallic coronary stents induce sustained vasomotor dysfunction, and preliminary observations from arteries with bioresorbable scaffolds have indicated partially restored vasoreactivity.

Methods: A total of 15 Absorb BVS (3.0 × 18.0 mm) and 14 XV (3.0 × 18.0 mm or 3.0 × 12.0 mm) stents were randomly implanted in the main coronaries of 12 nonatherosclerotic swine. The effect of implant on vasomotor performance (constrictive and expansive) was measured in the stented/scaffolded segments and the 5-mm proximal and distal adjacent segments in vivo by angiography assessing mean luminal diameter changes following infusion of vasoactive agents at 1 year (n = 6) and 2 years (n = 6) as well as ex vivo at 2 years using a tissue chamber apparatus. Endothelial cell function and smooth muscle cell phenotype gene marker levels were evaluated with quantitative real-time polymerase chain reaction.

Results: The scaffolded Absorb BVS segments showed fully restored constrictive response compared with XV implanted vessels at 1 year: -24.30 ± 14.31% versus -1.79 ± 6.57% (p < 0.004) and at 2 years: -28.13 ± 14.60% versus -3.90 ± 6.44% (p < 0.004). The early restoration of vasomotor function within the scaffolded segments reached a peak at 1 year and did not significantly change up to 2 years. The vasoactive responses of Absorb BVS-implanted vessels within the scaffolded segments were similar to those observed within the proximal and distal edge segments at both time points. Conversely, the stented XV segments demonstrated significantly impaired constrictive response compared with the distal XV edges at 1 year: -1.79 ± 6.57% versus -21.89 ± 7.17% (p < 0.0002) and at 2 years: -3.90 ± 6.44% versus -21.93 ± 15.60% (p < 0.03). Ex vivo assessment of contraction induced by PGF2α and relaxation induced by substance P of isolated BVS segments compared with XV-treated segments generated greater contraction force of 3.94 ± 0.97 g versus 1.83 ± 1.03 g (p < 0.05), and endothelial-dependent relaxation reached 35.91 ± 24.74% versus 1.20 ± 3.79% (p < 0.01). Quantitative real-time polymerase chain reaction gene analysis at 2 years demonstrated increased Connexin 43 messenger ribonucleic acid levels of Absorb BVS-treated vessels compared with XV-treated vessels: 1.92 ± 0.23 versus 0.77 ± 12 (p < 0.05).

Conclusions: Absorb BVS-implanted coronary arteries demonstrate early functional restoration of the scaffolded and adjacent segments at 1 year, which is preserved up to 2 years.
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http://dx.doi.org/10.1016/j.jcin.2015.12.018DOI Listing
April 2016

Novel 3-Dimensional Vessel and Scaffold Reconstruction Methodology for the Assessment of Strut-Level Wall Shear Stress After Deployment of Bioresorbable Vascular Scaffolds From the ABSORB III Imaging Substudy.

JACC Cardiovasc Interv 2016 Mar;9(5):501-3

Andreas Gruentzig Cardiovascular Center, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Emory Cardiovascular Imaging & Biomechanics Core Laboratory, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

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http://dx.doi.org/10.1016/j.jcin.2016.01.008DOI Listing
March 2016

Original Research: Sickle cell anemia and pediatric strokes: Computational fluid dynamics analysis in the middle cerebral artery.

Exp Biol Med (Maywood) 2016 04 4;241(7):755-65. Epub 2016 Mar 4.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA

Children with sickle cell anemia (SCA) have a high incidence of strokes, and transcranial Doppler (TCD) identifies at-risk patients by measuring blood velocities in large intracerebral arteries; time-averaged mean velocities greater than 200 cm/s confer high stroke risk and warrant therapeutic intervention with blood transfusions. Our objective was to use computational fluid dynamics to alter fluid and artery wall properties, to simulate scenarios causative of significantly elevated arterial blood velocities. Two-dimensional simulations were created and increasing percent stenoses were created in silico, with their locations varied among middle cerebral artery (MCA), internal carotid artery (ICA), and anterior cerebral artery (ACA). Stenoses placed in the MCA, ICA, or ACA generated local increases in velocity, but not sufficient to reach magnitudes > 200 cm/s, even up to 75% stenosis. Three-dimensional reconstructions of the MCA, ICA, and ACA from children with SCA were generated from magnetic resonance angiograms. Using finite element method, blood flow was simulated with realistic velocity waveforms to the ICA inlet. Three-dimensional reconstructions revealed an uneven, internal arterial wall surface in children with SCA and higher mean velocities in the MCA up to 145 cm/s compared to non-SCA reconstructions. There were also greater areas of flow recirculation and larger regions of low wall shear stress. Taken together, these bumps on the internal wall of the cerebral arteries could create local flow disturbances that, in aggregate, could elevate blood velocities in SCA. Identifying cellular causes of these microstructures as adhered blood cells or luminal narrowing due to endothelial hyperplasia induced by disturbed flow would provide new targets to treat children with SCA. The preliminary qualitative results provided here point out the critical role of 3D reconstruction of patient-specific vascular geometries and provide qualitative insight to complex interplay between vascular geometry and rheological properties possibly altered by SCA.
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http://dx.doi.org/10.1177/1535370216636722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950379PMC
April 2016

Association of Wall Shear Stress with Coronary Plaque Progression and Transformation.

Interv Cardiol Clin 2015 Oct 16;4(4):491-502. Epub 2015 Sep 16.

Interventional Cardiology, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1364 Clifton Road, Suite F606, Atlanta, GA 30322, USA. Electronic address:

Coronary endothelial function regulation by wall shear stress (WSS), the frictional force of blood exerted against the vessel wall, can help explain the focal propensity of plaque development in an environment of systemic atherosclerosis risk factors. Sustained abnormal pathologic WSS leads to a proatherogenic endothelial cell phenotype, plaque progression and transformation, and adaptive vascular remodeling in site-specific areas. Assessing dynamic coronary plaque compositional changes in vivo remains challenging; however, recent advances in intravascular image acquisition and processing may provide swifter WSS calculations and make possible larger prospective investigations on the prognostic value of WSS in patients with coronary atherosclerosis.
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http://dx.doi.org/10.1016/j.iccl.2015.06.009DOI Listing
October 2015

Aortic hemodynamics after thoracic endovascular aortic repair, with particular attention to the bird-beak configuration.

J Endovasc Ther 2014 Dec;21(6):791-802

1 Policlinico San Donato IRCCS, Thoracic Aortic Research Center, University of Milan, Italy.

Purpose: To quantitatively evaluate the impact of thoracic endovascular aortic repair (TEVAR) on aortic hemodynamics, focusing on the implications of a bird-beak configuration.

Methods: Pre- and postoperative CTA images from a patient treated with TEVAR for post-dissecting thoracic aortic aneurysm were used to evaluate the anatomical changes induced by the stent-graft and to generate the computational network essential for computational fluid dynamics (CFD) analysis. These analyses focused on the bird-beak configuration, flow distribution into the supra-aortic branches, and narrowing of the distal descending thoracic aorta. Three different CFD analyses (A: preoperative lumen, B: postoperative lumen, and C: postoperative lumen computed without stenosis) were compared at 3 time points during the cardiac cycle (maximum acceleration of blood flow, systolic peak, and maximum deceleration of blood flow).

Results: Postoperatively, disturbance of flow was reduced at the bird-beak location due to boundary conditions and change of geometry after TEVAR. Stent-graft protrusion with partial coverage of the origin of the left subclavian artery produced a disturbance of flow in this vessel. Strong velocity increase and flow disturbance were found at the aortic narrowing in the descending thoracic aorta when comparing B and C, while no effect was seen on aortic arch hemodynamics.

Conclusion: CFD may help physicians to understand aortic hemodynamic changes after TEVAR, including the change in aortic arch geometry, the effects of a bird-beak configuration, the supra-aortic flow distribution, and the aortic true lumen dynamics. This study is the first step in establishing a computational framework that, when completed with patient-specific data, will allow us to study thoracic aortic pathologies and their endovascular management.
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http://dx.doi.org/10.1583/14-4778MR.1DOI Listing
December 2014

Biomechanics and inflammation in atherosclerotic plaque erosion and plaque rupture: implications for cardiovascular events in women.

PLoS One 2014 3;9(11):e111785. Epub 2014 Nov 3.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia, United States of America; Cardiology Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America; Cardiology Division, Atlanta Veterans Affairs Medical Center, Decatur, Georgia, United States of America.

Objective: Although plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion.

Methods And Results: We studied a total of 74 human coronary plaque specimens obtained at autopsy. Using lesion-specific computer modeling of solid mechanics, we calculated the stress and strain distribution for each plaque and determined if there were any relationships with markers of inflammation. Consistent with previous studies, inflammatory markers were positively associated with increasing strain in specimens with rupture and thin-cap fibroatheromas. Conversely, overall staining for inflammatory markers and apoptosis were significantly lower in erosion, and there was no relationship with mechanical strain. Samples with plaque erosion most closely resembled those with the stable phenotype of thick-cap fibroatheromas.

Conclusions: In contrast to classic plaque rupture, plaque erosion was not associated with markers of inflammation and mechanical strain. These data suggest that plaque erosion is a distinct pathophysiological process with a different etiology and therefore raises the possibility that a different therapeutic approach may be required to prevent plaque erosion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111785PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218818PMC
November 2015

Surgical planning of the total cavopulmonary connection: robustness analysis.

Ann Biomed Eng 2015 Jun 15;43(6):1321-34. Epub 2014 Oct 15.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 387 Technology Circle, Suite 232, Atlanta, GA, 30313-2412, USA.

In surgical planning of the Fontan connection for single ventricle physiologies, there can be differences between the proposed and implemented options. Here, we developed a surgical planning framework that help determine the best performing option and ensures that the results will be comparable if there are slight geometrical variations. Eight patients with different underlying anatomies were evaluated in this study; surgical variations were created for each connection by changing either angle, offset or baffle diameter. Computational fluid dynamics were performed and the energy efficiency (indexed power loss-iPL) and hepatic flow distribution (HFD) computed. Differences with the original connection were evaluated: iPL was not considerably affected by the changes in geometry. For HFD, the single superior vena cava (SVC) connections presented less variability compared to the other anatomies. The Y-graft connection was the most robust overall, while the extra-cardiac connections showed dependency to offset. Bilateral SVC and interrupted inferior vena cava with azygous continuation showed high variability in HFD. We have developed a framework to assess the robustness of a surgical option for the TCPC; this will be useful to assess the most complex cases where pre-surgery planning could be most beneficial to ensure an efficient and robust hemodynamic performance.
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http://dx.doi.org/10.1007/s10439-014-1149-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398591PMC
June 2015

Computational fluid dynamics applied to virtually deployed drug-eluting coronary bioresorbable scaffolds: Clinical translations derived from a proof-of-concept.

Glob Cardiol Sci Pract 2014 31;2014(4):428-36. Epub 2014 Dec 31.

Andreas Gruentzig Cardiovascular Center, Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.

Background: Three-dimensional design simulations of coronary metallic stents utilizing mathematical and computational algorithms have emerged as important tools for understanding biomechanical stent properties, predicting the interaction of the implanted platform with the adjacent tissue, and informing stent design enhancements. Herein, we demonstrate the hemodynamic implications following virtual implantation of bioresorbable scaffolds using finite element methods and advanced computational fluid dynamics (CFD) simulations to visualize the device-flow interaction immediately after implantation and following scaffold resorption over time.

Methods And Results: CFD simulations with time averaged wall shear stress (WSS) quantification following virtual bioresorbable scaffold deployment in idealized straight and curved geometries were performed. WSS was calculated at the inflow, endoluminal surface (top surface of the strut), and outflow of each strut surface post-procedure (stage I) and at a time point when 33% of scaffold resorption has occurred (stage II). The average WSS at stage I over the inflow and outflow surfaces was 3.2 and 3.1 dynes/cm(2) respectively and 87.5 dynes/cm(2) over endoluminal strut surface in the straight vessel. From stage I to stage II, WSS increased by 100% and 142% over the inflow and outflow surfaces, respectively, and decreased by 27% over the endoluminal strut surface. In a curved vessel, WSS change became more evident in the inner curvature with an increase of 63% over the inflow and 66% over the outflow strut surfaces. Similar analysis at the proximal and distal edges demonstrated a large increase of 486% at the lateral outflow surface of the proximal scaffold edge.

Conclusions: The implementation of CFD simulations over virtually deployed bioresorbable scaffolds demonstrates the transient nature of device/flow interactions as the bioresorption process progresses over time. Such hemodynamic device modeling is expected to guide future bioresorbable scaffold design.
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http://dx.doi.org/10.5339/gcsp.2014.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355516PMC
March 2015

Computational Fluid Dynamics Simulations of Hemodynamics in Plaque Erosion.

Cardiovasc Eng Technol 2013 Dec;4(4)

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA 30332, USA.

Purpose: We investigated whether local hemodynamics were associated with sites of plaque erosion and hypothesized that patients with plaque erosion have locally elevated WSS magnitude in regions where erosion has occurred.

Methods: We generated 3D, patient-specific models of coronary arteries from biplane angiographic images in 3 human patients with plaque erosion diagnosed by optical coherence tomography (OCT). Using computational fluid dynamics, we simulated pulsatile blood flow and calculated both wall shear stress (WSS) and oscillatory shear index (OSI). We also investigated anatomic features of plaque erosion sites by examining branching and local curvature in x-ray angiograms of barium-perfused autopsy hearts.

Results: Neither high nor low magnitudes of mean WSS were associated with sites of plaque erosion. OSI and local curvature were also not associated with erosion. Anatomically, 8 of 13 hearts had a nearby bifurcation upstream of the site of plaque erosion.

Conclusions: This study provides preliminary evidence that neither hemodynamics nor anatomy are predictors of plaque erosion, based upon a very unique dataset. Our sample sizes are small, but this dataset suggests that high magnitudes of wall shear stress, one potential mechanism for inducing plaque erosion, are not necessary for erosion to occur.
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http://dx.doi.org/10.1007/s13239-013-0165-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819207PMC
December 2013

Biomechanical assessment of fully bioresorbable devices.

JACC Cardiovasc Interv 2013 Jul;6(7):760-1

Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

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http://dx.doi.org/10.1016/j.jcin.2013.04.008DOI Listing
July 2013

Inverse problems in Cardiovascular Mathematics: toward patient-specific data assimilation and optimization.

Int J Numer Method Biomed Eng 2013 Jul;29(7):723-5

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http://dx.doi.org/10.1002/cnm.2566DOI Listing
July 2013

Treatment planning for a TCPC test case: a numerical investigation under rigid and moving wall assumptions.

Int J Numer Method Biomed Eng 2013 Feb 29;29(2):197-216. Epub 2012 Sep 29.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, USA.

The hemodynamics in patients with total cavopulmonary connections (TCPC) is generally very complex and characterized by patient-to-patient variability. To better understand its effect on patients' outcome, CFD models are widely used, also to test and optimize surgical options before their implementation. These models often assume rigid geometries, despite the motion experienced by thoracic vessels that could influence the hemodynamics predictions. By improving their accuracy and expanding the range of simulated interventions, the benefit of treatment planning for patients is expected to increase. We simulate three types of intervention on a patient-specific 3D model, and compare their predicted outcome with baseline condition: a decrease in pulmonary vascular resistance obtainable with medications; a surgical revision of the connection design; the introduction of a fenestration in the TCPC wall. The simulations are performed both with rigid wall assumption and including patient-specific TCPC wall motion, reconstructed from a 4DMRI dataset. The results show the effect of each option on clinically important metrics and highlight the impact of patient-specific wall motion. The largest differences between rigid and moving wall models are observed in measures of energetic efficiency of TCPC as well as in hepatic flow distribution and transit time of seeded particles through the connection.
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http://dx.doi.org/10.1002/cnm.2517DOI Listing
February 2013

Biomechanical modeling and morphology analysis indicates plaque rupture due to mechanical failure unlikely in atherosclerosis-prone mice.

Am J Physiol Heart Circ Physiol 2013 Feb 30;304(3):H473-86. Epub 2012 Nov 30.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia 30322, USA.

Spontaneous plaque rupture in mouse models of atherosclerosis is controversial, although numerous studies have discussed so-called "vulnerable plaque" phenotypes in mice. We compared the morphology and biomechanics of two acute and one chronic murine model of atherosclerosis to human coronaries of the thin-cap fibroatheroma (TCFA) phenotype. Our acute models were apolipoprotein E-deficient (ApoE(-/-)) and LDL receptor-deficient (LDLr(-/-)) mice, both fed a high-fat diet for 8 wk with simultaneous infusion of angiotensin II (ANG II), and our chronic mouse model was the apolipoprotein E-deficient strain fed a regular chow diet for 1 yr. We found that the mouse plaques from all three models exhibited significant morphological differences from human TCFA plaques, including the plaque burden, plaque thickness, eccentricity, and amount of the vessel wall covered by lesion as well as significant differences in the relative composition of plaques. These morphological differences suggested that the distribution of solid mechanical stresses in the walls may differ as well. Using a finite-element analysis computational solid mechanics model, we computed the relative distribution of stresses in the walls of murine and human plaques and found that although human TCFA plaques have the highest stresses in the thin fibrous cap, murine lesions do not have such stress distributions. Instead, local maxima of stresses were on the media and adventitia, away from the plaque. Our results suggest that if plaque rupture is possible in mice, it may be driven by a different mechanism than mechanics.
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http://dx.doi.org/10.1152/ajpheart.00620.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774501PMC
February 2013

Numerical simulation of a susceptible-exposed-infectious space-continuous model for the spread of rabies in raccoons across a realistic landscape.

J Biol Dyn 2013 19;7 Suppl 1:31-46. Epub 2012 Nov 19.

a Department of Biostatistics , University of Washington , Seattle , WA , USA.

We introduce a numerical model for the spread of a lethal infectious disease in wildlife. The reference model is a Susceptible-Exposed-Infectious system where the spatial component of the dynamics is modelled by a diffusion process. The goal is to develop a model to be used for real geographical scenarios, so we do not rely upon simplifying assumptions on the shape of the region of interest. For this reason, space discretization is carried out with the finite element method on an unstructured triangulation. A diffusion term is designed to take into account landscape heterogeneities such as mountains and waterways. Numerical simulations are carried out for rabies epidemics among raccoons in New York state. A qualitative comparison of numerical results to available data from real-world epidemics is discussed.
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http://dx.doi.org/10.1080/17513758.2012.742578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957468PMC
July 2014