Abstract
In this work, we introduce a novel deep learning architecture, MUCRAN (Multi-Confound Regression Adversarial Network), to train a deep learning model on clinical brain MRI while regressing demographic and technical confounding factors. We trained MUCRAN using 17,076 clinical T1 Axial brain MRIs collected from Massachusetts General Hospital before 2019 and demonstrated that MUCRAN could successfully regress major confounding factors in the vast clinical dataset. We also applied a method for quantifying uncertainty across an ensemble of these models to automatically exclude out-of-distribution data in AD detection. By combining MUCRAN and the uncertainty quantification method, we showed consistent and significant increases in the AD detection accuracy for newly collected MGH data (post-2019; 84.6% with MUCRAN vs. 72.5% without MUCRAN) and for data from other hospitals (90.3% from Brigham and Women's Hospital and 81.0% from other hospitals). MUCRAN offers a generalizable approach for deep-learning-based disease detection in heterogenous clinical data.