Computational modeling of the right ventricle in repaired tetralogy of Fallot, before and after pulmonary valve replacement

Postprint (published version

Fluid dynamics of right ventricular filling in the presence of pulmonary regurgitation: assessment using DNS and 4D Flow MRI

Postprint (published version

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Blood Flow Dynamics at the Pulmonary Artery Bifurcation

Knowledge of physiologic hemodynamics is a fundamental requirement to establish pathological findings. However, little is known about the normal flow fields in the pulmonary arteries, especially for children. The purpose of this study is to characterize flow patterns in the pulmonary artery bifurcation of healthy pediatric subjects using direct numerical simulations. A realistic geometry is obtained via statistical shape modeling, by averaging five subject-specific digital models extracted from cardiovascular magnetic resonance datasets of healthy volunteers. Boundary conditions are assigned to mimic physiological conditions at rest, corresponding to a peak Reynolds number equal to 3400 and a Womersley number equal to 15. Results show that the normal bifurcation is highly hemodynamically efficient, as measured by an energy dissipation index. The curvature of the pulmonary arteries is sufficiently small to prevent flow separation along the inner walls, and no signs of a turbulent-like state are found. In line with previous imaging studies, a helical structure protruding into the right pulmonary artery is detected, and its formation mechanism is elucidated in the paper. These findings might help to identify abnormal flow features in patients with altered anatomic and physiologic states, particularly those with repaired congenital heart disease

Computational Modeling of Right Ventricular Motion and Intracardiac Flow in Repaired Tetralogy of Fallot.

PURPOSE: Patients with repaired Tetralogy of Fallot (rTOF) will develop dilation of the right ventricle (RV) from chronic pulmonary insufficiency and require pulmonary valve replacement (PVR). Cardiac MRI (cMRI) is used to guide therapy but has limitations in studying novel intracardiac flow parameters. This pilot study aimed to demonstrate feasibility of reconstructing RV motion and simulating intracardiac flow in rTOF patients, exclusively using conventional cMRI and an immersed-boundary method computational fluid dynamic (CFD) solver. METHODS: Four rTOF patients and three normal controls underwent cMRI including 4D flow. 3D RV models were segmented from cMRI images. Feature-tracking software captured RV endocardial contours from cMRI long-axis and short-axis cine stacks. RV motion was reconstructed via diffeomorphic mapping (Deformetrica, deformetrica.org), serving as the domain boundary for CFD. Fully-resolved direct numerical simulations were performed over several cardiac cycles. Intracardiac vorticity, kinetic energy (KE) and turbulent kinetic energy (TKE) was measured. For validation, RV motion was compared to manual tracings, results of KE were compared between CFD and 4D flow. RESULTS: Diastolic vorticity and TKE in rTOF patients were 4.12±2.42mJ/L and 115±27/s, compared to 2.96±2.16mJ/L and 78±45/s in controls. There was good agreement between RV motion and manual tracings. The difference in diastolic KE between CFD and 4D flow by Bland-Altman analysis was −0.89910-2 mJ/mL (95% limits of agreement: - 1.351*10(−2)mJ/mL to 1.171*10(−2)mJ/mL). CONCLUSION: This CFD framework can produce intracardiac flow in rTOF patients. CFD has the potential for predicting the effects of PVR in rTOF patients and improve the clinical indications guided by cMRI

Usage of 3D models of tetralogy of Fallot for medical education: impact on learning congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most common human birth defect, and clinicians need to understand the anatomy to effectively care for patients with CHD. However, standard two-dimensional (2D) display methods do not adequately carry the critical spatial information to reflect CHD anatomy. Three-dimensional (3D) models may be useful in improving the understanding of CHD, without requiring a mastery of cardiac imaging. The study aimed to evaluate the impact of 3D models on how pediatric residents understand and learn about tetralogy of Fallot following a teaching session. METHODS: Pediatric residents rotating through an inpatient Cardiology rotation were recruited. The sessions were randomized into using either conventional 2D drawings of tetralogy of Fallot or physical 3D models printed from 3D cardiac imaging data sets (cardiac MR, CT, and 3D echocardiogram). Knowledge acquisition was measured by comparing pre-session and post-session knowledge test scores. Learner satisfaction and self-efficacy ratings were measured with questionnaires filled out by the residents after the teaching sessions. Comparisons between the test scores, learner satisfaction and self-efficacy questionnaires for the two groups were assessed with paired t-test. RESULTS: Thirty-five pediatric residents enrolled into the study, with no significant differences in background characteristics, including previous clinical exposure to tetralogy of Fallot. The 2D image group (n = 17) and 3D model group (n = 18) demonstrated similar knowledge acquisition in post-test scores. Residents who were taught with 3D models gave a higher composite learner satisfaction scores (P = 0.03). The 3D model group also had higher self-efficacy aggregate scores, but the difference was not statistically significant (P = 0.39). CONCLUSION: Physical 3D models enhance resident education around the topic of tetralogy of Fallot by improving learner satisfaction. Future studies should examine the impact of models on teaching CHD that are more complex and elaborate

Statistical shape modeling reveals the link between right ventricular shape, hemodynamic force, and myocardial function in patients with repaired tetralogy of Fallot

Patients with repaired tetralogy of Fallot (rTOF) can develop chronic pulmonary insufficiency (PI) with right ventricular (RV) dilation, progressive RV dysfunction, and decreased exercise capacity. Pulmonary valve replacement (PVR) can help reduce the amount of PI and RV dilation; however, optimal timing remains controversial; a better understanding of rTOF pathophysiology is of fundamental importance to inform clinical management of patients with rTOF and optimal timing of PVR. In this study, we hypothesize a tight interplay between RV shape, intracardiac biomechanics, and ventricular function in patients with rTOF. To explore this hypothesis and derive quantitative measures, we combined statistical shape modeling with physics-based analysis of in vivo 4D flow data in 36 patients with rTOF. Our study demonstrated for the first time a correlation between regional RV shape variations, hemodynamic forces (HDF), and clinical dysfunction in patients with rTOF. The main findings of this work include 1) general increase in RV size, due to both volume overload and physiological growth, correlated with decrease in strain magnitude in the respective directions, and with increased QRS; 2) regional PI-induced remodeling accounted for ~10% of the shape variability of the population, and was associated with increased diastolic HDF along the diaphragm-to-right ventricular outflow tract (RVOT) direction, resulting in a net RV deformation along the same direction and decreased tricuspid annular plane systolic excursion (TAPSE); and 3) three shape modes independently correlated with systolic HDF and exercise capacity. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction and guide optimal timing of PVR.Peer ReviewedPostprint (author's final draft

Statistical shape modeling reveals the link between right ventricular shape, hemodynamic force, and myocardial function in repaired Tetralogy of Fallot patients

Repaired tetralogy of Fallot (rTOF) patients can develop chronic pulmonary insufficiency (PI) with right ventricular (RV) dilation, progressive RV dysfunction, and decreased exercise capacity. Pulmonary valve replacement (PVR) can help reduce the amount of PI and RV dilation, however optimal timing remains controversial; a better understanding of rTOF pathophysiology is of fundamental importance to inform clinical management of rTOF patients and optimal timing of PVR. In this study, we hypothesize a tight interplay between RV shape, intracardiac biomechanics and ventricular function in rTOF patients. To explore this hypothesis and derive quantitative measures, we combined statistical shape modeling with physics-based analysis of in-vivo 4D flow data in 36 rTOF patients. Our study demonstrated for the first time a correlation between regional RV shape variations, hemodynamic forces (HDF), and clinical dysfunction in rTOF patients. The main findings of this work include: i) general increase in RV size, due to both volume overload and physiologic growth, correlated with decrease in strain magnitude in the respective directions, and with increased QRS; ii) regional PI-induced remodeling accounted for ~10% of the shape variability of the population, and was associated with increased diastolic HDF along the diaphragm-to-RVOT direction, resulting in a net RV deformation along the same direction and decreased TAPSE; iii) three shape modes independently correlated with systolic HDF and exercise capacity. Identification of patients based on the shape variations described in this study could help identify those at risk for irreversible dysfunction and guide optimal timing of PVR