Multi-channel attention-fusion neural network for brain age estimation: Accuracy, generality, and interpretation with 16,705 healthy MRIs across lifespan

• Our new algorithm (FiA-Net) fuses contrast and morphometry information from MRI for age prediction. • We used 16,705 healthy brain MRIs 0-97 years of age for big-data and lifespan coverage. • The algorithm shows promise in accuracy, generality and interpretability. Brain age estimated by machine learning from T1-weighted magnetic resonance images (T1w MRIs) can reveal how brain disorders alter brain aging and can help in the early detection of such disorders. A fundamental step is to build an accurate age estimator from healthy brain MRIs. We focus on this step, and propose a framework to improve the accuracy, generality, and interpretation of age estimation in healthy brain MRIs. For accuracy, we used one of the largest sample sizes ( N = 16,705). For each subject, our proposed algorithm first explicitly splits the T1w image, which has been commonly treated as a single-channel 3D image in other studies, into two 3D image channels representing contrast and morphometry information. We further proposed a “fusion-with-attention” deep learning convolutional neural network (FiA-Net) to learn how to best fuse the contrast and morphometry image channels. FiA-Net recognizes varying contributions across image channels at different brain anatomy and different feature layers. In contrast, multi-channel fusion does not exist for brain age estimation, and is mostly attention-free in other medical image analysis tasks (e.g., image synthesis, or segmentation), where treating channels equally may not be optimal. For generality, we used lifespan data 0–97 years of age for real-world utility; and we thoroughly tested FiA-Net for multi-site and multi-scanner generality by two phases of cross-validations in discovery and replication data, compared to most other studies with only one phase of cross-validation. For interpretation, we directly measured each artificial neuron’s correlation with the chronological age, compared to other studies looking at the saliency of features where salient features may or may not predict age. Overall, FiA-Net achieved a mean absolute error (MAE) of 3.00 years and Pearson correlation r = 0.9840 with known chronological ages in healthy brain MRIs 0–97 years of age, comparing favorably with state-of-the-art algorithms and studies for accuracy and generality across sites and datasets. We also provided interpretations on how different artificial neurons and real neuroanatomy contribute to the age estimation.