Sander Land

Verification of cardiac tissue electrophysiology simulators using an N-version benchmark

Ongoing developments in cardiac modelling have resulted, in particular, in the development of advanced and increasingly complex computational frameworks for simulating cardiac tissue electrophysiology. The goal of these simulations is often to represent the detailed physiology and pathologies of the heart using codes that exploit the computational potential of high-performance computing architectures. These developments have rapidly progressed the simulation capacity of cardiac virtual physiological human style models; however, they have also made it increasingly challenging to verify that a given code provides a faithful representation of the purported governing equations and corresponding solution techniques. This study provides the first cardiac tissue electrophysiology simulation benchmark to allow these codes to be verified. The benchmark was successfully evaluated on 11 simulation platforms to generate a consensus gold-standard converged solution. The benchmark definition in combination with the gold-standard solution can now be used to verify new simulation codes and numerical methods in the future.

The estimation of patient-specific cardiac diastolic functions from clinical measurements

An unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual active tension (AT) because of the impaired ventricular relaxation during diastole. To address this problem, this paper presents a method for estimating diastolic mechanical parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. Dynamic C1-continuous meshes are automatically built from the anatomy and deformation captured from dynamic MRI sequences. Diastolic deformation is simulated using a mechanical model that combines passive and active material properties. The problem of non-uniqueness of constitutive parameter estimation using the well known Guccione law is characterized by reformulation of this law. Using this reformulated form, and by constraining the constitutive parameters to be constant across time points during diastole, we separate the effects of passive constitutive properties and the residual AT during diastolic relaxation. Finally, the method is applied to two clinical cases and one control, demonstrating that increased residual AT during diastole provides a potential novel index for delineating healthy and pathological cases.

An analysis of deformation‐dependent electromechanical coupling in the mouse heart

•  The amount of force generated by heart cells is strongly influenced by feedback from the deformation of cardiac tissue, both from the changes in cell length and the rate at which cells are stretched. •  We analysed the effect these cellular mechanisms have on whole heart function by making a computational model of mouse heart cells, and embedding this cellular model into a representation of the heart. •  Unlike previous murine models, this model represents the heart at both body temperature and the high heart rates seen in these animals, allowing us to directly compare results from our computational model with experimental measurements. •  Results show that effects from the rate of stretch are especially important for explaining the large differences observed between force generated by isolated cells and pressure measured experimentally. •  The model also provides an important framework for future research focused on interpreting results from genetic manipulation experiments in mice.

Efficient Computational Methods for Strongly Coupled Cardiac Electromechanics

Strongly coupled cardiac electromechanical models can further our understanding of the relative importance of feedback mechanisms in the heart, but computational challenges currently remain a major obstacle, which limit their widespread use. To address this issue, we present a set of efficient computational methods including an efficient adaptive cell model integration scheme and a solution method for the monodomain equations that maintains high conduction velocity for time steps greater than 0.1 ms. We also present a novel method for increasing the efficiency of simulating electromechanical coupling, which shows a significant reduction in computational cost of the mechanical component on a personalized left ventricular geometry with an active contraction cell model reparametrized for human cells.

An automatic service for the personalization of ventricular cardiac meshes

Computational cardiac physiology has great potential to improve the management of cardiovascular diseases. One of the main bottlenecks in this field is the customization of the computational model to the anatomical and physiological status of the patient. We present a fully automatic service for the geometrical personalization of cardiac ventricular meshes with high-order interpolation from segmented images. The method is versatile (able to work with different species and disease conditions) and robust (fully automatic results fulfilling accuracy and quality requirements in 87% of 255 cases). Results also illustrate the capability to minimize the impact of segmentation errors, to overcome the sparse resolution of dynamic studies and to remove the sometimes unnecessary anatomical detail of papillary and trabecular structures. The smooth meshes produced can be used to simulate cardiac function, and in particular mechanics, or can be used as diagnostic descriptors of anatomical shape by cardiologists. This fully automatic service is deployed in a cloud infrastructure, and has been made available and accessible to the scientific community.

Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour

Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.

MED-NODE

Melanoma is an aggressive type of skin difficult to differentiate from benign naevi.We present an expert system that assists physicians with this task.The system uses color and texture lesion descriptors from non-dermoscopic images.The system also uses a set of visual attributes provided by the examining physician.The proposed system achieves high diagnostic accuracy results (81%). Melanoma is one of the most aggressive types of skin cancer and in many cases it is difficult to differentiate from benign naevi. In this contribution we present a decision support (expert) system, which we call MED-NODE, able to assist physicians with this challenging task. The proposed system makes use of non-dermoscopic digital images of lesions from which it automatically extracts the lesion regions and then computes descriptors regarding the color and texture. In addition, a set of visual attributes is provided by the examining physician. The automatically extracted descriptors and the attributes provided by the physician are separately used for automatic prediction. Final classification is achieved by a majority vote of all predictions. The proposed system achieves high diagnostic accuracy results (81%) and performs comparably to state-of-the-art methods that are using dermoscopic images, though such images contain more detailed information and are subject to less noise and illumination effects. The simple input requirements and the robustness of its descriptors allow MED-NODE to be an effective tool within the diagnostic process for melanoma. In addition, the modular nature of the system allows for it to be easily extended.

Quality Metrics for High Order Meshes: Analysis of the Mechanical Simulation of the Heart Beat

The quality of a computational mesh is an important characteristic for stable and accurate simulations. Quality depends on the regularity of the initial mesh, and in mechanical simulations it evolves in time, with deformations causing changes in volume and distortion of mesh elements. Mesh quality metrics are therefore relevant for both mesh personalization and the monitoring of the simulation process. This work evaluates the significance, in meshes with high order interpolation, of four quality metrics described in the literature, applying them to analyse the stability of the simulation of the heart beat. It also investigates how image registration and mesh warping parameters affect the quality and stability of meshes. Jacobian-based metrics outperformed or matched the results of coarse geometrical metrics of aspect ratio or orthogonality, although they are more expensive computationally. The stability of simulations of a complete heart cycle was best predicted with a specificity of 61%, sensitivity of 85%, and only nominal differences were found changing the intra-element and per-element combination of quality values. A compromise between fitting accuracy and mesh stability and quality was found. Generic geometrical quality metrics have a limited success predicting stability, and an analysis of the simulation problem may be required for an optimal definition of quality.

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Experimental data from human cardiac myocytes at body temperature is crucial for a quantitative understanding of clinically relevant cardiac function and development of whole-organ computational models. However, such experimental data is currently very limited. Specifically, important measurements to characterize changes in tension development in human cardiomyocytes that occur with perturbations in cell length are not available. To address this deficiency, in this study we present an experimental data set collected from skinned human cardiac myocytes, including the passive and viscoelastic properties of isolated myocytes, the steady-state force calcium relationship at different sarcomere lengths, and changes in tension following a rapid increase or decrease in length, and after constant velocity shortening. This data set is, to our knowledge, the first characterization of length and velocity-dependence of tension generation in human skinned cardiac myocytes at body temperature. We use this data to develop a computational model of contraction and passive viscoelasticity in human myocytes. Our model includes troponin C kinetics, tropomyosin kinetics, a three-state crossbridge model that accounts for the distortion of crossbridges, and the cellular viscoelastic response. Each component is parametrized using our experimental data collected in human cardiomyocytes at body temperature. Furthermore we are able to confirm that properties of length-dependent activation at 37°C are similar to other species, with a shift in calcium sensitivity and increase in maximum tension. We revise our model of tension generation in the skinned isolated myocyte to replicate reported tension traces generated in intact muscle during isometric tension, to provide a model of human tension generation for multi-scale simulations. This process requires changes to calcium sensitivity, cooperativity, and crossbridge transition rates. We apply this model within multi-scale simulations of biventricular cardiac function and further refine the parametrization within the whole organ context, based on obtaining a healthy ejection fraction. This process reveals that crossbridge cycling rates differ between skinned myocytes and intact myocytes.

An automatic data assimilation framework for patient-specific myocardial mechanical parameter estimation

We present an automatic workflow to extract myocardial constitutive parameters from clinical data. Our framework assimilates cine and 3D tagged Magnetic Resonance Images (MRI) together with left ventricular (LV) cavity pressure recordings to characterize the mechanics of the LV. Dynamic C1-continuous meshes are automatically fitted using both the cine MRI and 4D displacement fields extracted from the tagged MRI. The passive filling of the LV is simulated, with patient-specific geometry, kinematic boundary and loading conditions. The mechanical parameters are identified by matching the simulated diastolic deformation to observed end-diastolic displacements. We applied our framework to two heart failure patient cases and one normal case. The results indicate that while an end-diastolic measurement does not constrain the mechanical parameters uniquely, it does provide a potentially robust indicator of myocardial stiffness.