From a deep learning model back to the brain - inferring morphological markers and their relation to aging

We present a Deep Learning framework for the prediction of chronological age from structural MRI scans. Previous findings associate an overestimation of brain age with neurodegenerative diseases and higher mortality rates. However, the importance of brain age prediction goes beyond serving as biomarkers for neurological disorders. Specifically, utilizing convolutional neural network (CNN) analysis to identify brain regions contributing to the prediction can shed light on the complex multivariate process of brain aging. Previous work examined methods to attribute pixel/voxel-wise contributions to the prediction in a single image, resulting in explanation maps that were found noisy and unreliable. To address this problem, we developed an inference framework for combining these maps across subjects, thus creating a population-based rather than a subject-specific map. We applied this method to a CNN ensemble trained on predicting subjects age from raw T1 brain images of 10,176 subjects. Evaluating the model on an untouched test set resulted in mean absolute error of 3.07 years and a correlation between chronological and predicted age of r=0.98. Using the inference method, we revealed that cavities containing CSF, previously found as general atrophy markers, had the highest contribution for age prediction. Comparing maps derived from different models within the ensemble allowed to assess differences and similarities in brain regions utilized by the model. We showed that this method substantially increased the replicability of explanation maps, converged with results from voxel-based morphometry age studies and highlighted brain regions whose volumetric variability contributed the most to the prediction.\n\nHighlightsO_LICNNs ensemble is shown to estimate \"brain age\" from sMRI with an MAE of [~]3.1 years\nC_LIO_LIA novel framework enables to highlight brain regions contributing to the prediction\nC_LIO_LIThis framework results in explanation maps showing consistency with the literature\nC_LIO_LIAs sample size increases, these maps show higher inter-sample replicability\nC_LIO_LICSF cavities reflecting general atrophy were found as a prominent aging biomarker\nC_LI