Parameter estimation in a cardiovascular computational model using numerical optimization : Patient simulation, searching for a digital twin

Sammanfattning: Developing models of the cardiovascular system that simulates the dynamic behavior of a virtual patient’s condition is fundamental in the medical domain for predictive outcome and hypothesis generation. These models are usually described through Ordinary Differential Equation (ODE). To obtain a patient-specific representative model, it is crucial to have an accurate and rapid estimate of the hemodynamic model parameters. Moreover, when adequate model parameters are found, the resulting time series of state variables can be clinically used for predicting the response to treatments and for non-invasive monitoring. In the Thesis, we address the parameter estimation or inverse modeling, by solving an optimization problem, which aims at minimizing the error between the model output and the target data. In our case, the target data are a set of user-defined state variables, descriptive of a hospitalized specific patient and obtained from time-averaged state variables. The Thesis proposes a comparison of both state-of-the-art and novel methods for the estimation of the underlying model parameters of a cardiovascular simulator Aplysia. All the proposed algorithms are selected and implemented considering the constraints deriving from the interaction with Aplysia. In particular, given the inaccessibility of the ODE, we selected gradient-free methods, which do not need to estimate numerically the derivatives. Furthermore, we aim at having a small number of iterations and objective function calls, since these importantly impact the speed of the estimation procedure, and thus the applicability of the knowledge gained through the parameters at the bedside. Moreover, the Thesis addresses the most common problems encountered in the inverse modeling, among which are the non-convexity of the objective function and the identifiability problem. To assist in resolving the latter issue an identifiability analysis is proposed, after which the unidentifiable parameters are excluded. The selected methods are validated using heart failure data, representative of different pathologies commonly encountered in Intensive Care Unit (ICU) patients. The results show that the gradient-free global algorithms Enhanced Scatter Search and Particle Swarm estimate the parameters accurately at the price of a high number of function evaluations and CPU time. As such, they are not suitable for bedside applications. Besides, the local algorithms are not suitable to find an accurate solution given their dependency on the initial guess. To solve this problem, we propose two methods: the hybrid, and the prior-knowledge algorithms. These methods, by including prior domain knowledge, can find a good solution, escaping the basin of attraction of local minima and producing clinically significant parameters in a few minutes.