Generalizable and explainable deep learning for brain MRI: a multi-cohort evaluation of 3D architectures for age and sex prediction
Brain Informatics, vol. 13
Abstract
Deep learning (DL) methods increasingly outperform classical approaches in brain MRI analysis, yet their generalizability across independent imaging cohorts remains insufficiently evaluated. Because age and sex are fundamental neurobiological factors influencing brain structure and disease risk, this study systematically compares three three-dimensional architectures-Simple Fully Convolutional Network (SFCN), DenseNet121, and Swin Transformer-for age and sex prediction using T1-weighted MRI from four independent cohorts: UK Biobank (UKB, n = 47,390), Dallas Lifespan Brain Study (DLBS, n = 132), Parkinson's Progression Markers Initiative (PPMI, n = 108 controls), and Information eXtraction from Images (IXI, n = 319). SFCN consistently demonstrated the most robust performance. For sex classification, it achieved an AUC of 1.00 [1.00-1.00] in the UKB internal test set and 0.85-0.91 across external cohorts. For age prediction, SFCN achieved a mean absolute error (MAE) of 2.66 years (r = 0.89) internally and 4.98-5.81 years (r = 0.55-0.70) externally. Pairwise DeLong and Wilcoxon tests with Bonferroni correction confirmed significantly better performance of SFCN compared with Swin Transformer in most cohorts (p < 0.017). No significant demographic subgroup biases were observed. Explainability analyses further showed task-specific and spatially consistent attention patterns across cohorts. These findings demonstrate that simpler convolutional architectures can generalize more reliably than more complex attention-based models in multi-cohort settings. The study highlights the importance of external validation and emphasizes potential trade-offs between model complexity, robustness, and interpretability for clinically relevant neuroimaging applications.
Authors 12
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
Institute and Polyclinic for Diagnostic and Interventional Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus Dresden, Technical University Dresden, Dresden, Germany
-
Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
University Hospital Carl Gustav Carus · Technische Universität Dresden
Affiliation as printed
Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany
-
University Hospital Carl Gustav Carus · Technische Universität Dresden
Affiliation as printed
Institute of Diagnostic and Interventional Neuroradiology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany
-
Universitätsklinikum Aachen · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Department of Diagnostic and Interventional Radiology, University Hospital Aachen, Aachen, Germany
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany
-
Affiliation as printed
Department of Diagnostic and Interventional Radiology, University Hospital Aachen, Aachen, Germany
-
Jakob Nikolas Kather corresponding
University of Leeds · University Hospital Heidelberg · National Center for Tumor Diseases · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Department of Medicine I, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany. kather.jn@tu-dresden.de
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany. kather.jn@tu-dresden.de
Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany. kather.jn@tu-dresden.de
Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK. kather.jn@tu-dresden.de
Cited by 0 stored of 0
No patents citing this paper on Lens.org (checked 2026-10-06).