Christopher T. Villongco

Patient-specific models of cardiac biomechanics

Patient-specific models of cardiac function have the potential to improve diagnosis and management of heart disease by integrating medical images with heterogeneous clinical measurements subject to constraints imposed by physical first principles and prior experimental knowledge. We describe new methods for creating three-dimensional patient-specific models of ventricular biomechanics in the failing heart. Three-dimensional bi-ventricular geometry is segmented from cardiac CT images at end-diastole from patients with heart failure. Human myofiber and sheet architecture is modeled using eigenvectors computed from diffusion tensor MR images from an isolated, fixed human organ-donor heart and transformed to the patient-specific geometric model using large deformation diffeomorphic mapping. Semi-automated methods were developed for optimizing the passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Material properties of active cardiac muscle contraction were optimized to match ventricular pressures measured by cardiac catheterization, and parameters of a lumped-parameter closed-loop model of the circulation were estimated with a circulatory adaptation algorithm making use of information derived from echocardiography. These components were then integrated to create a multi-scale model of the patient-specific heart. These methods were tested in five heart failure patients from the San Diego Veterans Affairs Medical Center who gave informed consent. The simulation results showed good agreement with measured echocardiographic and global functional parameters such as ejection fraction and peak cavity pressures.

Patient-Specific Modeling of Dyssynchronous Heart Failure: A Case Study

The development and clinical use of patient-specific models of the heart is now a feasible goal. Models have the potential to aid in diagnosis and support decision-making in clinical cardiology. Several groups are now working on developing multi-scale models of the heart for understanding therapeutic mechanisms and better predicting clinical outcomes of interventions such as cardiac resynchronization therapy. Here we describe the methodology for generating a patient-specific model of the failing heart with a myocardial infarct and left ventricular bundle branch block. We discuss some of the remaining challenges in developing reliable patient-specific models of cardiac electromechanical activity, and identify some of the main areas for focusing future research efforts. Key challenges include: efficiently generating accurate patient-specific geometric meshes and mapping regional myofiber architecture to them; modeling electrical activation patterns based on cellular alterations in human heart failure, and estimating regional tissue conductivities based on clinically available electrocardiographic recordings; estimating unloaded ventricular reference geometry and material properties for biomechanical simulations; and parameterizing systemic models of circulatory dynamics from available hemodynamic measurements.

An Atlas-Based Geometry Pipeline for Cardiac Hermite Model Construction and Diffusion Tensor Reorientation

Here we present a novel atlas-based geometry pipeline for constructing three-dimensional cubic Hermite finite element meshes of the whole human heart from tomographic patient image data. To build the cardiac atlas, two superior atria, two inferior ventricles as well as the aorta and the pulmonary trunk are first segmented, and epicardial and endocardial boundary surfaces are extracted and smoothed. Critical points and skeletons (or central-line paths) are identified, following the cardiac topology. The surface model and the path tree are used to construct a hexahedral control mesh via a skeleton-based sweeping method. Derivative parameters are computed from the control mesh, defining cubic Hermite finite elements. The thickness of the atria and the ventricles is obtained using segmented epicardial boundaries or via offsetting from the endocardial surfaces in regions where the image resolution is insufficient. We also develop a robust optical flow approach to deform the constructed atlas and align it with the image from a second patient. This registration method is fully-automatic, and avoids manual operations required by segmentation and path extraction. Moreover, we demonstrate that this method can also be used to deformably map diffusion tensor MRI data with patient geometries to include fiber and sheet orientations in the finite element model.

High-order finite element methods for cardiac monodomain simulations

Computational modeling of tissue-scale cardiac electrophysiology requires numerically converged solutions to avoid spurious artifacts. The steep gradients inherent to cardiac action potential propagation necessitate fine spatial scales and therefore a substantial computational burden. The use of high-order interpolation methods has previously been proposed for these simulations due to their theoretical convergence advantage. In this study, we compare the convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed cubic Hermite-style serendipity interpolation methods for finite element simulations of the cardiac monodomain equation. The high-order methods reach converged solutions with fewer degrees of freedom and longer element edge lengths than traditional linear elements. Additionally, we propose a dimensionless number, the cell Thiele modulus, as a more useful metric for determining solution convergence than element size alone. Finally, we use the cell Thiele modulus to examine convergence criteria for obtaining clinically useful activation patterns for applications such as patient-specific modeling where the total activation time is known a priori.

Non-invasive, model-based measures of ventricular electrical dyssynchrony for predicting CRT outcomes

AIMS Left ventricular activation delay due to left bundle branch block (LBBB) is an important determinant of the severity of dyssynchronous heart failure (DHF). We investigated whether patient-specific computational models constructed from non-invasive measurements can provide measures of baseline dyssynchrony and its reduction after CRT that may explain the degree of long-term reverse ventricular remodelling. METHODS AND RESULTS LV end-systolic volume reduction (ΔESVLV) measured by 2D trans-thoracic echocardiography in eight patients following 6 months of CRT was significantly (P < 0.05) greater in responders (26 ± 20%, n = 4) than non-responders (11 ± 16%, n = 4). LV reverse remodelling did not correlate with baseline QRS duration or its change after biventricular pacing, but did correlate with baseline LV endocardial activation measured by electroanatomic mapping (R2 = 0.71, P < 0.01). Patient-specific models of LBBB ventricular activation with parameters obtained by matching model-computed vectorcardiograms (VCG) to those derived from standard patient ECGs yielded LV endocardial activation times that correlated well with those measured from endocardial maps (R2 = 0.90). Model-computed 3D LV activation times correlated strongly with the reduction in LVESV (R2 = 0.93, P < 0.001). Computed decreases due to simulated CRT in the time delay between LV septal and lateral activation correlated strongly with ΔESVLV (R2 = 0.92, P < 0.001). Models also suggested that optimizing VV delays may improve resynchronization by this measure of activation delay. CONCLUSIONS Patient-specific computational models constructed from non-invasive measurements can compute estimates of LV dyssynchrony and their changes after CRT that may be as good as or better than electroanatomic mapping for predicting long-term reverse remodelling.

Affine transformation registers small scale lung deformation

To evaluate the nature of small scale lung deformation between multiple pulmonary magnetic resonance images, two different kinematic intensity based image registration techniques: affine and bicubic Hermite interpolation were tested. The affine method estimates uniformly distributed deformation metrics throughout the lung. The bicubic Hermite method allows the expression of heterogeneously distributed deformation metrics such as Lagrangian strain. A cardiac triggered inversion recovery technique was used to obtain 10 sequential images of pulmonary vessel structure in a sagittal plane in the right lung at FRC in 4 healthy subjects (Age: 28.5(6.2)). One image was used as the reference image, and the remaining images (target images) were warped onto the reference image using both image registration techniques. The normalized correlation between the reference and the transformed target images within the lung domain was used as a cost function for optimization, and the root mean square (RMS) of image intensity difference was used to evaluate the quality of the registration. Both image registration techniques significantly improved the RMS compared with non-registered target images (p= 0.04). The spatial mean (μE) and standard deviation (σE) of Lagrangian strain were computed based on the spatial distribution of lung deformation approximated by the bicubic Hermite method, and were measured on the order of 10-3 or less, which is virtually negligible. As a result, small scale lung deformation between FRC lung volumes is spatially uniform, and can be simply characterized by affine deformation even though the bicubic Hermite method is capable of expressing complicated spatial patterns of lung deformation.

Myofiber prestretch magnitude determines regional systolic function during ectopic activation in the tachycardia-induced failing canine heart

Electrical dyssynchrony leads to prestretch in late-activated regions and alters the sequence of mechanical contraction, although prestretch and its mechanisms are not well defined in the failing heart. We hypothesized that in heart failure, fiber prestretch magnitude increases with the amount of early-activated tissue and results in increased end-systolic strains, possibly due to length-dependent muscle properties. In five failing dog hearts with scars, three-dimensional strains were measured at the anterolateral left ventricle (LV). Prestretch magnitude was varied via ventricular pacing at increasing distances from the measurement site and was found to increase with activation time at various wall depths. At the subepicardium, prestretch magnitude positively correlated with the amount of early-activated tissue. At the subendocardium, local end-systolic strains (fiber shortening, radial wall thickening) increased proportionally to prestretch magnitude, resulting in greater mean strain values in late-activated compared with early-activated tissue. Increased fiber strains at end systole were accompanied by increases in preejection fiber strain, shortening duration, and the onset of fiber relengthening, which were all positively correlated with local activation time. In a dog-specific computational failing heart model, removal of length and velocity dependence on active fiber stress generation, both separately and together, alter the correlations between local electrical activation time and timing of fiber strains but do not primarily account for these relationships.

Rotors exhibit greater Surface ECG variation during ventricular fibrillation than focal sources due to wavebreak, secondary rotors, and meander

Ventricular fibrillation is a common life‐threatening arrhythmia. The ECG of VF appears chaotic but may allow identification of sustaining mechanisms to guide therapy.

Left Ventricular Diastolic and Systolic Material Property Estimation from Image Data

Cardiovascular simulations using patient-specific geometries can help researchers understand the mechanical behavior of the heart under different loading or disease conditions. However, to replicate the regional mechanics of the heart accurately, both the nonlinear passive and active material properties must be estimated reliably. In this paper, automated methods were used to determine passive material properties while simultaneously computing the unloaded reference geometry of the ventricles for stress analysis. Two different approaches were used to model systole. In the first, a physiologically-based active contraction model [1] coupled to a hemodynamic three-element Windkessel model of the circulation was used to simulate ventricular ejection. In the second, developed active tension was directly adjusted to match ventricular volumes at end-systole while prescribing the known end-systolic pressure. These methods were tested in four normal dogs using the data provided for the LV mechanics challenge [2]. The resulting end-diastolic and end-systolic geometry from the simulation were compared with measured image data .

Successful Ventricular Fibrillation Functional Substrate Ablation via a Single Vascular Access Site

Introduction Ventricular fibrillation (VF) is a common cause of sudden cardiac death worldwide. Patients with clinical VF may receive frequent implantable cardioverter-defibrillator (ICD) shocks and suffer poor quality of life. In patients who fail antiarrhythmic medications and do not have identifiable triggers for VF, such as premature ventricular contractions (PVCs) or monomorphic ventricular tachycardia (VT), there are currently limited options. However, recent work has demonstrated the importance of rotor substrate in maintaining VF, and that suppression of VF may be achieved via substrate ablation using either endocardial basket catheter phase mapping or electrocardiographic imaging to localize VF sources. Prior reported cases were performed with multiple venous and atrial access sheaths to facilitate mapping and ablation. It is unclear, however, if similar efficacy can safely be achieved with limited vascular access and without access to the right ventricle (RV). Additionally, the presence and prevalence of late potentials