Biophysics-based statistical learning: Application to heart and brain interactions.

Initiatives such as the UK Biobank provide joint cardiac and brain imaging information for thousands of individuals, representing a unique opportunity to study the relationship between heart and brain. Most of research on large multimodal databases has been focusing on studying the associations among the available measurements by means of univariate and multivariate association models. However, these approaches do not provide insights about the underlying mechanisms and are often hampered by the lack of prior knowledge on the physiological relationships between measurements. For instance, important indices of the cardiovascular function, such as cardiac contractility, cannot be measured in-vivo. While these non-observable parameters can be estimated by means of biophysical models, their personalisation is generally an ill-posed problem, often lacking critical data and only applied to small datasets. Therefore, to jointly study brain and heart, we propose an approach in which the parameter personalisation of a lumped cardiovascular model is constrained by the statistical relationships observed between model parameters and brain-volumetric indices extracted from imaging, i.e. ventricles or white matter hyperintensities volumes, and clinical information such as age or body surface area. We explored the plausibility of the learnt relationships by inferring the model parameters conditioned on the absence of part of the target clinical features, applying this framework in a cohort of more than 3 000 subjects and in a pathological subgroup of 59 subjects diagnosed with atrial fibrillation. Our results demonstrate the impact of such external features in the cardiovascular model personalisation by learning more informative parameter-space constraints. Moreover, physiologically plausible mechanisms are captured through these personalised models as well as significant differences associated to specific clinical conditions.