Airflow and particle deposition simulations in health and emphysema: from in vivo to in silico animal experiments.

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.

Simulation based planning of surgical interventions in pediatric cardiology.

Hemodynamics plays an essential role in the progression and treatment of cardiovascular disease. However, while medical imaging provides increasingly detailed anatomical information, clinicians often have limited access to hemodynamic data that may be crucial to patient risk assessment and treatment planning. Computational simulations can now provide detailed hemodynamic data to augment clinical knowledge in both adult and pediatric applications.

A non-discrete method for computation of residence time in fluid mechanics simulations.

Cardiovascular simulations provide a promising means to predict risk of thrombosis in grafts, devices, and surgical anatomies in adult and pediatric patients. Although the pathways for platelet activation and clot formation are not yet fully understood, recent findings suggest that thrombosis risk is increased in regions of flow recirculation and high residence time (RT). Current approaches for calculating RT are typically based on releasing a finite number of Lagrangian particles into the flow field and calculating RT by tracking their positions.

Moving domain computational fluid dynamics to interface with an embryonic model of cardiac morphogenesis.

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.

Numerical blood flow simulation in surgical corrections: what do we need for an accurate analysis?

Background: 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.

Friction force microscopy: a simple technique for identifying graphene on rough substrates and mapping the orientation of graphene grains on copper.

At a single atom thick, it is challenging to distinguish graphene from its substrate using conventional techniques. In this paper we show that friction force microscopy (FFM) is a simple and quick technique for identifying graphene on a range of samples, from growth substrates to rough insulators. We show that FFM is particularly effective for characterizing graphene grown on copper where it can correlate the graphene growth to the three-dimensional surface topography.

An efficient framework for optimization and parameter sensitivity analysis in arterial growth and remodeling computations.

Computational models for vascular growth and remodeling (G&R) are used to predict the long-term response of vessels to changes in pressure, flow, and other mechanical loading conditions. Accurate predictions of these responses are essential for understanding numerous disease processes. Such models require reliable inputs of numerous parameters, including material properties and growth rates, which are often experimentally derived, and inherently uncertain.

Lagrangian analysis of hemodynamics data from FSI simulation.

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.

Variability of computational fluid dynamics solutions for pressure and flow in a giant aneurysm: the ASME 2012 Summer Bioengineering Conference CFD Challenge.

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.

Optimization of a Y-graft design for improved hepatic flow distribution in the fontan circulation.

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.

An integrated approach to patient-specific predictive modeling for single ventricle heart palliation.

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.

Self-trimerization of ExsD limits inhibition of the Pseudomonas aeruginosa transcriptional activator ExsA in vitro.

The opportunistic pathogen Pseudomonas aeruginosa ranks among the leading causes of nosocomial infection. The type III secretion system (T3SS) aids acute Pseudomonas aeruginosa infection by injecting potent cytotoxins into host cells to suppress the host's innate immune response. Expression of all T3SS-related genes is strictly dependent on the transcription factor ExsA.

Predictive modeling of the virtual Hemi-Fontan operation for second stage single ventricle palliation: two patient-specific cases.

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.

Optimization of shunt placement for the Norwood surgery using multi-domain modeling.

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.

Identification of hemodynamically optimal coronary stent designs based on vessel caliber.

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.

Fluid-structure interaction simulations of the Fontan procedure using variable wall properties.

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.

Patient-specific multiscale modeling of blood flow for coronary artery bypass graft surgery.

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.

Optimization of cardiovascular stent design using computational fluid dynamics.

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.

Rat airway morphometry measured from in situ MRI-based geometric models.

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).

Orientation of Pseudomonas aeruginosa ExsA monomers bound to promoter DNA and base-specific contacts with the P(exoT) promoter.

ExsA is a transcriptional activator of the Pseudomonas aeruginosa type III secretion system (T3SS) and a member of the AraC/XylS protein family. Each of the 10 ExsA-dependent promoter regions that define the T3SS regulon has two adjacent binding sites for monomeric ExsA. Whereas the promoter-proximal sites (binding site 1) contain highly conserved GnC and TGnnA sequences that are separated by ∼10 bp, the promoter-distal sites (binding site 2) share no obvious sequence similarity to each other or to the binding site 1 consensus.

The distal ExsA-binding site in Pseudomonas aeruginosa type III secretion system promoters is the primary determinant for promoter-specific properties.

Transcription of the Pseudomonas aeruginosa type III secretion system is controlled by ExsA, a member of the AraC/XylS family of regulators. Each ExsA-dependent promoter contains two adjacent binding sites for monomeric ExsA. The promoter-proximal site (binding site 1) consists of highly conserved GnC and TGnnA sequences that are individually recognized by the two helix-turn-helix (HTH) DNA-binding motifs of an ExsA monomer.

Image-based modeling of hemodynamics in coronary artery aneurysms caused by Kawasaki disease.

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.

Virtual surgeries in patients with congenital heart disease: a multi-scale modelling test case.

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.

Hepatic blood flow distribution and performance in conventional and novel Y-graft Fontan geometries: a case series computational fluid dynamics study.

Objectives: 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.