Probabilistic learning of the Purkinje network from the electrocardiogram

correct definition of cardiac digital twins for precision cardiology. Here, we propose a probabilistic approach for identifying the Purkinje network from non-invasive clinical data such as the standard electrocardiogram (ECG). We use cardiac imaging to build an anatomically accurate model of the ventricles; we algorithmically generate a rule-based Purkinje network tailored to the anatomy; we simulate physiological electrocardiograms with a fast model; we identify the geometrical and electrical parameters of the Purkinje-ECG model with Bayesian optimization and approximate Bayesian computation. The proposed approach is inherently probabilistic and generates a population of plausible Purkinje networks, all fitting the ECG within a given tolerance. In this way, we can estimate the uncertainty of the parameters, thus providing reliable predictions. We test our methodology in physiological and pathological scenarios, showing that we are able to accurately recover the ECG with our model. We propagate the uncertainty in the Purkinje network parameters in a simulation of conduction system pacing therapy. Our methodology is a step forward in creation of digital twins from non-invasive data in precision medicine. An open source implementation can be found at http://github.com/fsahli/purkinjelearning.