SummaryA central problem in biomechanical studies of personalized human left ventricular modelling is estimating the material properties and biophysical parameters from in vivo clinical measurements in a timeframe that is suitable for use within a clinic. Understanding these properties can provide insight into heart function or dysfunction and help to inform personalized medicine. However, finding a solution to the differential equations which mathematically describe the kinematics and dynamics of the myocardium through numerical integration can be computationally expensive. To circumvent this issue, we use the concept of emulation to infer the myocardial properties of a healthy volunteer in a viable clinical timeframe by using in vivo magnetic resonance image data. Emulation methods avoid computationally expensive simulations from the left ventricular model by replacing the biomechanical model, which is defined in terms of explicit partial differential equations, with a surrogate model inferred from simulations generated before the arrival of a patient, vastly improving computational efficiency at the clinic. We compare and contrast two emulation strategies: emulation of the computational model outputs and emulation of the loss between the observed patient data and the computational model outputs. These strategies are tested with two interpolation methods, as well as two loss functions. The best combination of methods is found by comparing the accuracy of parameter inference on simulated data for each combination. This combination, using the output emulation method, with local Gaussian process interpolation and the Euclidean loss function, provides accurate parameter inference in both simulated and clinical data, with a reduction in the computational cost of about three orders of magnitude compared with numerical integration of the differential equations by using finite element discretization techniques.

In recent years, we have witnessed substantial advances in the mathematical modelling of the biomechanical processes underlying the dynamics of the cardiac soft-tissue. Gao et al. (Gao et al. 2017 J. R. Soc. Interface 14 , 20170203 ( doi:10.1098/rsif.2017.0203 )) demonstrated that the parameters underlying the biomechanical model have diagnostic value for prognosticating the risk of myocardial infarction. However, the computational costs of parameter estimation are prohibitive when the goal lies in building real-time clinical decision support systems. This is due to the need to repeatedly solve the mathematical equations numerically using finite-element discretization during an iterative optimization routine. The present article presents a method for accelerating the inference of the constitutive parameters by using statistical emulation with Gaussian processes. We demonstrate how the computational costs can be reduced by about three orders of magnitude, with hardly any loss in accuracy, and we assess various alternative techniques in a comparative evaluation study based on simulated data obtained by solving the left ventricular model with the finite-element method, and real magnetic resonance images data for a human volunteer.

We consider parameter inference in cardio‐mechanic models of the left ventricle, in particular the one based on the Holtzapfel‐Ogden (HO) constitutive law, using clinical in vivo data. The equations underlying these models do not admit closed form solutions and hence need to be solved numerically. These numerical procedures are computationally expensive making computational run times associated with numerical optimisation or sampling excessive for the uptake of the models in the clinical practice. To address this issue, we adopt the framework of Bayesian optimisation (BO), which is an efficient statistical technique of global optimisation. BO seeks the optimum of an unknown black‐box function by sequentially training a statistical surrogate‐model and using it to select the next query point by leveraging the associated exploration‐exploitation trade‐off. To guarantee that the estimates based on the in vivo data are realistic also for high‐pressures, unobservable in vivo, we include a penalty term based on a previously published empirical law developed using ex vivo data. Two case studies based on real data demonstrate that the proposed BO procedure outperforms the state‐of‐the‐art inference algorithm for the HO constitutive law.

Personalized computational cardiac models are considered to be a unique and powerful tool in modern cardiology, integrating the knowledge of physiology, pathology and fundamental laws of mechanics in one framework. They have the potential to improve risk prediction in cardiac patients and assist in the development of new treatments. However, in order to use these models for clinical decision support, it is important that both the impact of model parameter perturbations on the predicted quantities of interest as well as the uncertainty of parameter estimation are properly quantified, where the first task is a priori in nature (meaning independent of any specific clinical data), while the second task is carried out a posteriori (meaning after specific clinical data have been obtained). The present study addresses these challenges for a widely used constitutive law of passive myocardium (the Holzapfel-Ogden model), using global sensitivity analysis (SA) to address the first challenge, and inverse-uncertainty quantification (I-UQ) for the second challenge. The SA is carried out on a range of different input parameters to a left ventricle (LV) model, making use of computationally efficient Gaussian process (GP) surrogate models in place of the numerical forward simulator. The results of the SA are then used to inform a low-order reparametrization of the constitutive law for passive myocardium under consideration. The quality of this parameterization in the context of an inverse problem having observed noisy experimental data is then quantified with an I-UQ study, which again makes use of GP surrogate models. The I-UQ is carried out in a Bayesian manner using Markov Chain Monte Carlo, which allows for full uncertainty quantification of the material parameter estimates. Our study reveals insights into the relation between SA and I-UQ, elucidates the dependence of parameter sensitivity and estimation uncertainty on external factors, like LV cavity pressure, and sheds new light on cardio-mechanic model formulation, with particular focus on the Holzapfel-Ogden myocardial model.

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