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Cardiomyocytes are the functional building blocks of the heart—yet most models developed to simulate cardiac mechanics do not represent the individual cells and their surrounding matrix. Instead, they work on a homogenized tissue level, assuming that cellular and subcellular structures and processes scale uniformly. Here we present a mathematical and numerical framework for exploring tissue-level cardiac mechanics on a microscale given an explicit three-dimensional geometrical representation of cells embedded in a matrix. We defined a mathematical model over such a geometry and parametrized our model using publicly available data from tissue stretching and shearing experiments. We then used the model to explore mechanical differences between the extracellular and the intracellular space. Through sensitivity analysis, we found the stiffness in the extracellular matrix to be most important for the intracellular stress values under contraction. Strain and stress values were observed to follow a normal-tangential pattern concentrated along the membrane, with substantial spatial variations both under contraction and stretching. We also examined how it scales to larger size simulations, considering multicellular domains. Our work extends existing continuum models, providing a new geometrical-based framework for exploring complex cell–cell and cell–matrix interactions.

Computational models of the heart have reached a level of maturity that enables sophisticated patient-specific simulations and hold potential for important applications in diagnosis and therapy planning. However, such clinical use puts strict demands on the reliability and accuracy of the models and requires the sensitivity of the model predictions due to errors and uncertainty in the model inputs to be quantified. The models typically contain a large number of parameters, which are difficult to measure and therefore associated with considerable uncertainty. Additionally, patient-specific geometries are usually constructed by semi-manual processing of medical images and must be assumed to be a potential source of model uncertainty. In this paper, we assess the model accuracy by considering the impact of geometrical uncertainties, which typically occur in image-based computational geometries. An approach based on 17 AHA segments diagram is used to consider uncertainties in wall thickness and also in the material properties and fiber orientation, and we perform a comprehensive uncertainty quantification and sensitivity analysis based on polynomial chaos expansions. The quantities considered include stress, strain and global deformation parameters of the left ventricle. The results indicate that important quantities of interest may be more affected by wall thickness, and highlight the need for accurate geometry reconstructions in patient-specific cardiac mechanics models.

In myocardial infarction, muscle tissue of the heart is damaged as a result of ceased or severely impaired blood flow. Survivors have an increased risk of further complications, possibly leading to heart failure. Material properties play an important role in determining post-infarction outcome. Due to spatial variation in scarring, material properties can be expected to vary throughout the tissue of a heart after an infarction. In this study we propose a data assimilation technique that can efficiently estimate heterogeneous elastic material properties in a personalized model of cardiac mechanics. The proposed data assimilation is tested on a clinical dataset consisting of regional left ventricular strains and in vivo pressures during atrial systole from a human with a myocardial infarction. Good matches to regional strains are obtained, and simulated equi-biaxial tests are carried out to demonstrate regional heterogeneities in stress–strain relationships. A synthetic data test shows a good match of estimated versus ground truth material parameter fields in the presence of no to low levels of noise. This study is the first to apply adjoint-based data assimilation to the important problem of estimating cardiac elastic heterogeneities in 3-D from medical images.

Cardiac muscle tissue during relaxation is commonly modeled as a hyperelastic material with strongly nonlinear and anisotropic stress response. Adapting the behavior of such a model to experimental or patient data gives rise to a parameter estimation problem which involves a significant number of parameters. Gradient-based optimization algorithms provide a way to solve such nonlinear parameter estimation problems with relatively few iterations, but require the gradient of the objective functional with respect to the model parameters. This gradient has traditionally been obtained using finite differences, the calculation of which scales linearly with the number of model parameters, and introduces a differencing error. By using an automatically derived adjoint equation, we are able to calculate this gradient more efficiently, and with minimal implementation effort. We test this adjoint framework on a least squares fitting problem involving data from simple shear tests on cardiac tissue samples. A second challenge which arises in gradient-based optimization is the dependency of the algorithm on a suitable initial guess. We show how a multi-start procedure can alleviate this dependency. Finally, we provide estimates for the material parameters of the Holzapfel and Ogden strain energy law using finite element models together with experimental shear data.

An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non-contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased.