Accounting for inter-individual variability in brain function is key to precision medicine. Here, by considering functional inter-individual variability as meaningful data rather than noise, we introduce VarCoNet, an enhanced self-supervised framework for robust functional connectome (FC) extraction from resting-state fMRI (rs-fMRI) data. VarCoNet employs self-supervised contrastive learning to exploit inherent functional inter-individual variability, serving as a brain function encoder that generates FC embeddings readily applicable to downstream tasks even in the absence of labeled data. Contrastive learning is facilitated by a novel augmentation strategy based on segmenting rs-fMRI signals. At its core, VarCoNet integrates a 1D-CNN-Transformer encoder for advanced time-series processing, enhanced with a robust Bayesian hyperparameter optimization. Our VarCoNet framework is evaluated on two downstream tasks: (i) subject fingerprinting, using rs-fMRI data from the Human Connectome Project, and (ii) autism spectrum disorder (ASD) classification, using rs-fMRI data from the ABIDE I and ABIDE II datasets. Using different brain parcellations, our extensive testing against state-of-the-art methods, including 13 deep learning methods, demonstrates VarCoNet's superiority, robustness, interpretability, and generalizability. Overall, VarCoNet provides a versatile and robust framework for FC analysis in rs-fMRI.

Brain atlases are essential for reducing the dimensionality of neuroimaging data and enabling interpretable analysis. However, most existing atlases are predefined, group-level templates with limited flexibility and resolution. We present Deep Cluster Atlas (DCA), a graph-guided deep embedding clustering framework for generating individualized, voxel-wise brain parcellations. DCA combines a pretrained autoencoder with spatially regularized deep clustering to produce functionally coherent and spatially contiguous regions. Our method supports flexible control over resolution and anatomical scope, and generalizes to arbitrary brain structures. We further introduce a standardized benchmarking platform for atlas evaluation, using multiple large-scale fMRI datasets. Across multiple datasets and scales, DCA outperforms state-of-the-art atlases, improving functional homogeneity by 98.8% and silhouette coefficient by 29%, and achieves superior performance in downstream tasks such as autism diagnosis and cognitive decoding. We also observe that a fine-tuned pretrained model achieves superior results on the corresponding task. Codes and models are available at https://github.com/ncclab-sustech/DCA .

As large language models (LLMs) continue to revolutionize AI research, there is a growing interest in building large-scale brain foundation models to advance neuroscience. While most existing brain foundation models are pre-trained on time-series signals or connectome features, we propose a novel graph-based pre-training paradigm for constructing a brain graph foundation model. In this paper, we introduce the Brain Graph Foundation Model, termed BrainGFM, a unified framework that leverages graph contrastive learning and graph masked autoencoders for large-scale fMRI-based pre-training. BrainGFM is pre-trained on a diverse mixture of brain atlases with varying parcellations, significantly expanding the pre-training corpus and enhancing the model's ability to generalize across heterogeneous fMRI-derived brain representations. To support efficient and versatile downstream transfer, we integrate both graph prompts and language prompts into the model design, enabling BrainGFM to flexibly adapt to a wide range of atlases, neurological and psychiatric disorders, and task settings. Furthermore, we employ meta-learning to optimize the graph prompts, facilitating strong generalization to previously unseen disorders under both few-shot and zero-shot learning conditions via language-guided prompting. BrainGFM is pre-trained on 27 neuroimaging datasets spanning 25 common neurological and psychiatric disorders, encompassing 2 types of brain atlases (functional and anatomical) across 8 widely-used parcellations, and covering over 25,000 subjects, 60,000 fMRI scans, and a total of 400,000 graph samples aggregated across all atlases and parcellations. The code is available at: https://github.com/weixinxu666/BrainGFM

Magnetic resonance imaging of fetal and neonatal brains reveals rapid neurodevelopment marked by substantial anatomical changes unfolding within days. Studying this critical stage of the developing human brain, therefore, requires accurate brain models-referred to as atlases-of high spatial and temporal resolution. To meet these demands, established traditional atlases and recently proposed deep learning-based methods rely on large and comprehensive datasets. This poses a major challenge for studying brains in the presence of pathologies for which data remains scarce. We address this limitation with CINeMA (Conditional Implicit Neural Multi-Modal Atlas), a novel framework for creating high-resolution, spatio-temporal, multimodal brain atlases, suitable for low-data settings. Unlike established methods, CINeMA operates in latent space, avoiding compute-intensive image registration and reducing atlas construction times from days to minutes. Furthermore, it enables flexible conditioning on anatomical features including GA, birth age, and pathologies like ventriculomegaly (VM) and agenesis of the corpus callosum (ACC). CINeMA supports downstream tasks such as tissue segmentation and age prediction whereas its generative properties enable synthetic data creation and anatomically informed data augmentation. Surpassing state-of-the-art methods in accuracy, efficiency, and versatility, CINeMA represents a powerful tool for advancing brain research. We release the code and atlases at https://github.com/m-dannecker/CINeMA.

We present MultiMorph, a fast and efficient method for constructing anatomical atlases on the fly. Atlases capture the canonical structure of a collection of images and are essential for quantifying anatomical variability across populations. However, current atlas construction methods often require days to weeks of computation, thereby discouraging rapid experimentation. As a result, many scientific studies rely on suboptimal, precomputed atlases from mismatched populations, negatively impacting downstream analyses. MultiMorph addresses these challenges with a feedforward model that rapidly produces high-quality, population-specific atlases in a single forward pass for any 3D brain dataset, without any fine-tuning or optimization. MultiMorph is based on a linear group-interaction layer that aggregates and shares features within the group of input images. Further, by leveraging auxiliary synthetic data, MultiMorph generalizes to new imaging modalities and population groups at test-time. Experimentally, MultiMorph outperforms state-of-the-art optimization-based and learning-based atlas construction methods in both small and large population settings, with a 100-fold reduction in time. This makes MultiMorph an accessible framework for biomedical researchers without machine learning expertise, enabling rapid, high-quality atlas generation for diverse studies.

In the realm of neuroscience, identifying distinctive patterns associated with neurological disorders via brain networks is crucial. Resting-state functional magnetic resonance imaging (fMRI) serves as a primary tool for mapping these networks by correlating blood-oxygen-level-dependent (BOLD) signals across different brain regions, defined as regions of interest (ROIs). Constructing these brain networks involves using atlases to parcellate the brain into ROIs based on various hypotheses of brain division. However, there is no standard atlas for brain network classification, leading to limitations in detecting abnormalities in disorders. Some recent methods have proposed utilizing multiple atlases, but they neglect consistency across atlases and lack ROI-level information exchange. To tackle these limitations, we propose an Atlas-Integrated Distillation and Fusion network (AIDFusion) to improve brain network classification using fMRI data. AIDFusion addresses the challenge of utilizing multiple atlases by employing a disentangle Transformer to filter out inconsistent atlas-specific information and distill distinguishable connections across atlases. It also incorporates subject- and population-level consistency constraints to enhance cross-atlas consistency. Additionally, AIDFusion employs an inter-atlas message-passing mechanism to fuse complementary information across brain regions. Experimental results on four datasets of different diseases demonstrate the effectiveness and efficiency of AIDFusion compared to state-of-the-art methods. A case study illustrates AIDFusion extract patterns that are both interpretable and consistent with established neuroscience findings.

Anatomical atlases are widely used for population analysis. Conditional atlases target a particular sub-population defined via certain conditions (e.g. demographics or pathologies) and allow for the investigation of fine-grained anatomical differences - such as morphological changes correlated with age. Existing approaches use either registration-based methods that are unable to handle large anatomical variations or generative models, which can suffer from training instabilities and hallucinations. To overcome these limitations, we use latent diffusion models to generate deformation fields, which transform a general population atlas into one representing a specific sub-population. By generating a deformation field and registering the conditional atlas to a neighbourhood of images, we ensure structural plausibility and avoid hallucinations, which can occur during direct image synthesis. We compare our method to several state-of-the-art atlas generation methods in experiments using 5000 brain as well as whole-body MR images from UK Biobank. Our method generates highly realistic atlases with smooth transformations and high anatomical fidelity, outperforming the baselines.

Congenital Heart Disease (CHD) is a group of cardiac malformations present already during fetal life, representing the prevailing category of birth defects globally. Our aim in this study is to aid 3D fetal vessel topology visualisation in aortic arch anomalies, a group which encompasses a range of conditions with significant anatomical heterogeneity. We present a multi-task framework for automated multi-class fetal vessel segmentation from 3D black blood T2w MRI and anomaly classification. Our training data consists of binary manual segmentation masks of the cardiac vessels' region in individual subjects and fully-labelled anomaly-specific population atlases. Our framework combines deep learning label propagation using VoxelMorph with 3D Attention U-Net segmentation and DenseNet121 anomaly classification. We target 11 cardiac vessels and three distinct aortic arch anomalies, including double aortic arch, right aortic arch, and suspected coarctation of the aorta. We incorporate an anomaly classifier into our segmentation pipeline, delivering a multi-task framework with the primary motivation of correcting topological inaccuracies of the segmentation. The hypothesis is that the multi-task approach will encourage the segmenter network to learn anomaly-specific features. As a secondary motivation, an automated diagnosis tool may have the potential to enhance diagnostic confidence in a decision support setting. Our results showcase that our proposed training strategy significantly outperforms label propagation and a network trained exclusively on propagated labels. Our classifier outperforms a classifier trained exclusively on T2w volume images, with an average balanced accuracy of 0.99 (0.01) after joint training. Adding a classifier improves the anatomical and topological accuracy of all correctly classified double aortic arch subjects.

Age prediction is an important part of medical assessments and research. It can aid in detecting diseases as well as abnormal ageing by highlighting the discrepancy between chronological and biological age. To gain a comprehensive understanding of age-related changes observed in various body parts, we investigate them on a larger scale by using whole-body 3D images. We utilise the Grad-CAM interpretability method to determine the body areas most predictive of a person's age. We expand our analysis beyond individual subjects by employing registration techniques to generate population-wide interpretability maps. Our findings reveal three primary areas of interest: the spine, the autochthonous back muscles, and the cardiac region, which exhibits the highest importance.

Segmentation and spatial alignment of ultrasound (US) imaging data acquired in the in first trimester are crucial for monitoring human embryonic growth and development throughout this crucial period of life. Current approaches are either manual or semi-automatic and are therefore very time-consuming and prone to errors. To automate these tasks, we propose a multi-atlas framework for automatic segmentation and spatial alignment of the embryo using deep learning with minimal supervision. Our framework learns to register the embryo to an atlas, which consists of the US images acquired at a range of gestational age (GA), segmented and spatially aligned to a predefined standard orientation. From this, we can derive the segmentation of the embryo and put the embryo in standard orientation. US images acquired at 8+0 till 12+6 weeks GA were used and eight subjects were selected as atlas. We evaluated different fusion strategies to incorporate multiple atlases: 1) training the framework using atlas images from a single subject, 2) training the framework with data of all available atlases and 3) ensembling of the frameworks trained per subject. To evaluate the performance, we calculated the Dice score over the test set. We found that training the framework using all available atlases outperformed ensembling and gave similar results compared to the best of all frameworks trained on a single subject. Furthermore, we found that selecting images from the four atlases closest in GA out of all available atlases, regardless of the individual quality, gave the best results with a median Dice score of 0.72. We conclude that our framework can accurately segment and spatially align the embryo in first trimester 3D US images and is robust for the variation in quality that existed in the available atlases.