Automated model calibration with parallel MCMC: Applications for a cardiovascular system model

Computational physiological models continue to increase in complexity, however, the task of efficiently calibrating the model to available clinical data remains a significant challenge. One part of this challenge is associated with long calibration times, which present a barrier for the routine application of model-based prediction in clinical practice. Another aspect of this challenge is the limited available data for the unique calibration of complex models. Therefore, to calibrate a patient-specific model, it may be beneficial to verify that task-specific model predictions have acceptable uncertainty, rather than requiring all parameters to be uniquely identified. We have developed a pipeline that reduces the set of fitting parameters to make them structurally identifiable and to improve the efficiency of a subsequent Markov Chain Monte Carlo (MCMC) analysis. MCMC was used to find the optimal parameter values and to determine the confidence interval of a task-specific prediction. This approach was demonstrated on numerical experiments where a lumped parameter model of the cardiovascular system was calibrated to brachial artery cuff pressure, echocardiogram volume measurements, and synthetic cerebral blood flow data that approximates what can be obtained from 4D-flow MRI data. This pipeline provides a cerebral arterial pressure prediction that may be useful for determining the risk of hemorrhagic stroke. For a set of three patients, this pipeline successfully reduced the parameter set of a cardiovascular system model from 12 parameters to 8–10 structurally identifiable parameters. This enabled a significant [Formula: see text] efficiency improvement in determining confidence intervals on predictions of pressure compared to performing a naive MCMC analysis with the full parameter set. This demonstrates the potential that the proposed pipeline has in helping address one of the key challenges preventing clinical application of such models. Additionally, for each patient, the MCMC approach yielded a 95% confidence interval on systolic blood pressure prediction in the middle cerebral artery smaller than ±10 mmHg (±1.3 kPa). The proposed pipeline exploits available high-performance computing parallelism to allow straightforward automation for general models and arbitrary data sets, enabling automated calibration of a parameter set that is specific to the available clinical data with minimal user interaction.