Understanding Sources of Demographic Predictability in Brain MRI via Disentangling Anatomy and Contrast
Authors: Mehmet Yigit Avci, Akshit Achara, Andrew King, Jorge Cardoso
Organizations: and for the Alzheimer's Disease Neuroimaging Initiative · School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK
Demographic attributes can be predicted from medical images, raising concerns about bias in clinical AI systems. In X-ray imaging, acquisition characteristics have been shown to contribute substantially to this predictability. Whether the same holds in brain MRI remains unclear, as anatomical variation and acquisition-dependent contrast are deeply entangled in the image formation process, obscuring the origins of demographic signal. To address this, we propose a controlled framework based on disentangled representation learning, decomposing brain MRI into anatomy-focused representations that suppress acquisition influence and contrast embeddings that capture acquisition-dependent characteristics. Training predictive models for age, sex, and race on full images, anatomical representations, and contrast embeddings allows us to quantify the relative contributions of structure and acquisition to the demographic signal. Across three datasets and multiple MRI sequences, demographic predictability is found to be driven primarily by anatomical variation, with anatomy-focused representations largely preserving the performance of models trained on raw images. Contrast embeddings retain a weaker signal that is dataset-specific and does not generalise across sites. These findings suggest that effective mitigation must explicitly account for the primarily anatomical and secondarily acquisition-dependent origins of demographic signal, ensuring that any bias reduction generalizes robustly across domains.
Biomedical imaging data exhibit substantial acquisition variability, where identical biological structures can appear markedly different due to differences in imaging devices, acquisition protocols, sites, and reconstruction settings. Consequently, learned representations often entangle underlying biological information with acquisition-dependent appearance, limiting interpretability, generalisation, and clinical deployment. We show that these sources of variation can be disentangled by jointly modelling medical images and acquisition metadata. Using large-scale clinical brain MRI data as a case study, we learn representations that disentangle anatomical structure from contrast-dependent appearance. The resulting framework enables the organisation of heterogeneous imaging protocols, sequence understanding, the detection of image-metadata inconsistencies and imaging artifacts, while preserving biologically relevant anatomical features across diverse acquisitions. Building on these disentangled representations, it further supports generative and translational capabilities, performing both metadata-conditioned synthesis of realistic 3D brain MRIs and anatomy-preserving harmonisation for cross-modality and cross-site adaptation. Our findings demonstrate that acquisition variability is a structured component of the imaging process that can be modeled, audited, synthesised, and controlled, establishing a foundation for acquisition-aware representation learning in large-scale biomedical imaging.
Mehmet Yigit Avci, Pedro Borges, Virginia Fernandez +5
Self-supervised learning offers a compelling approach for medical imaging, where labeled data are scarce and acquisition costs are high. We present COJEPA, a self-supervised framework for volumetric brain MRI that combines a joint-embedding predictive architecture (JEPA) with a contrastive loss (CO), targeting two complementary properties: local predictivity and global discriminability. The model is trained without labels on T1-weighted structural MRI from two cohorts (HCP-YA and AABC, N=2286, ages 22 to 90), extending I-JEPA to 3D with foreground-aware block masking, a hierarchical convolutional patch embedding, and world-space sinusoidal positional encodings. We evaluate all three objectives across zero-shot twin retrieval, brain tumor segmentation (BraTS 2024), and age regression (OpenBHB). COJEPA achieves the best monozygotic twin recall at rank@1 (0.84), the best finetuning age MAE (2.55 years on OpenBHB 3.0T), and matches CO on BraTS whole-tumor Dice, demonstrating that the combined objective yields representations that are simultaneously discriminative and locally structured.
Synthetic training has recently advanced brain MRI segmentation by enabling contrast-agnostic models trained entirely on generated data. However, most existing approaches rely on hundreds of automatically labeled templates, introducing systematic biases and limiting their flexibility to incorporate new anatomical structures. We present the Segment It All Model (SIAM), a 3D whole-head segmentation framework for 16 anatomical structures, trained using only six high-quality, manually annotated templates. SIAM extends domain randomization to both intensity and shape domains: synthetic image generation ensures contrast variability, while high-resolution spatial transformations model anatomical differences in cortical thickness and deep nuclei morphology. Unlike prior synthetic models, SIAM simultaneously segments brain as well as extra-cerebral tissues, including cerebrospinal fluid, vessels, dura mater, skull, and skin, enabling fully automated, preprocessing-free analysis. Evaluation across eight heterogeneous datasets (N=301), that include multiple contrasts (T1-weighted, T2-weighted, CT) and span a wide range of ages, demonstrates that SIAM matches or outperforms state-of-the-art methods for brain structures, in addition to extending automated segmentation to non-brain structures. The model also exhibits superior consistency across contrasts and repeated acquisitions, together with improved sensitivity to subtle gray matter atrophy. We openly release the model and the label templates at https://github.com/romainVala/SIAM.