OpenMAP-BrainAge: Generalizable and Interpretable Brain Age Predictor

Purpose: To develop an age prediction model which is interpretable and robust to demographic and technological variances in brain MRI scans. Materials and Methods: We propose a transformer-based architecture that leverages self-supervised pre-training on large-scale datasets. Our model processes pseudo-3D T1-weighted MRI scans from three anatomical views and incorporates brain volumetric information. By introducing a stem architecture, we reduce the conventional quadratic complexity of transformer models to linear complexity, enabling scalability for high-dimensional MRI data. We trained our model on ADNI2 & 3 (N=1348) and OASIS3 (N=716) datasets (age range: 42 - 95) from the North America, with an 8:1:1 split for train, validation and test. Then, we validated it on the AIBL dataset (N=768, age range: 60 - 92) from Australia. Results: We achieved an MAE of 3.65 years on ADNI2 & 3 and OASIS3 test set and a high generalizability of MAE of 3.54 years on AIBL. There was a notable increase in brain age gap (BAG) across cognitive groups, with mean of 0.15 years (95% CI: [-0.22, 0.51]) in CN, 2.55 years ([2.40, 2.70]) in MCI, 6.12 years ([5.82, 6.43]) in AD. Additionally, significant negative correlation between BAG and cognitive scores was observed, with correlation coefficient of -0.185 (p < 0.001) for MoCA and -0.231 (p < 0.001) for MMSE. Gradient-based feature attribution highlighted ventricles and white matter structures as key regions influenced by brain aging. Conclusion: Our model effectively fused information from different views and volumetric information to achieve state-of-the-art brain age prediction accuracy, improved generalizability and interpretability with association to neurodegenerative disorders.