Deep learning techniques have demonstrated great potential for accurately estimating brain age by analyzing Magnetic Resonance Imaging (MRI) data from healthy individuals. However, current methods for brain age estimation often directly utilize whole input images, overlooking two important considerations: 1) the heterogeneous nature of brain aging, where different brain regions may degenerate at different rates, and 2) the existence of age-independent redundancies in brain structure. To overcome these limitations, we propose a Dual Graph Attention based Disentanglement Multi-instance Learning (DGA-DMIL) framework for improving brain age estimation. Specifically, the 3D MRI data, treated as a bag of instances, is fed into a 2D convolutional neural network backbone, to capture the unique aging patterns in MRI. A dual graph attention aggregator is then proposed to learn the backbone features by exploiting the intra- and inter-instance relationships. Furthermore, a disentanglement branch is introduced to separate age-related features from age-independent structural representations to ameliorate the interference of redundant information on age prediction. To verify the effectiveness of the proposed framework, we evaluate it on two datasets, UK Biobank and ADNI, containing a total of 35,388 healthy individuals. Our proposed model demonstrates exceptional accuracy in estimating brain age, achieving a remarkable mean absolute error of 2.12 years in the UK Biobank. The results establish our approach as state-of-the-art compared to other competing brain age estimation models. In addition, the instance contribution scores identify the varied importance of brain areas for aging prediction, which provides deeper insights into the understanding of brain aging.
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