Uncertainty Estimation and Explainability in Deep Learning-Based Age Estimation of the Human Brain: Results from the German National Cohort MRI Study.

Brain ageing is a complex neurobiological process associated with morphological changes that can be assessed on MRI scans. Recently, Deep learning (DL)-based approaches have been proposed for the prediction of chronological brain age from MR images yielding high accuracy. These approaches, however, usually do not address quantification of uncertainty and, therefore, intrinsic physiological variability. Considering uncertainty is essential for the interpretation of the difference between predicted and chronological age. In addition, DL-based models lack in explainability compared to classical approaches like voxel-based morphometry. In this study, we aim to address both, modeling uncertainty and providing visual explanations to explore physiological patterns in brain ageing. T1-weighted brain MRI datasets of 10691 participants of the German National Cohort Study, drawn from the general population, were included in this study (chronological age from 20 to 72 years). A regression model based on a 3D Convolutional Neural Network taking into account aleatoric noise was implemented for global as well as regional brain age estimation. We observed high overall accuracy of global brain age estimation with a mean absolute error of 3.2 +/- 2.5 years and mean uncertainty of 2.9 +/- 0.6 years. Regional brain age estimation revealed higher estimation accuracy and lower uncertainty in central compared to peripheral brain regions. Visual explanations illustrating the importance of brain sub-regions were generated using Grad-CAM: the derived saliency maps showed a high relevance of the lateral and third ventricles, the insular lobe as well as parts of the basal ganglia and the internal capsule.