Brain-MRI inpainting replaces a masked region of a scan with synthesized, anatomically plausible healthy tissue, so that analysis tools built for healthy brains can be applied to images they would otherwise reject. On the BraTS local-synthesis benchmark, which ranks submissions on the structural similarity index (SSIM), the peak signal-to-noise ratio, and the mean squared error (MSE) jointly, the strongest recent models are accurate, but several report blurry synthesized regions and attribute this to the mean-seeking behavior of the $\ell_1$ and MSE terms in their training losses. We address this in post-processing, forming a deep ensemble of the two co-first-place 2025 models and training a lightweight residual refiner on the ensemble's own outputs under an $\ell_1$ loss augmented with a structural-similarity term whose weight $λ$ we vary. At a moderate $λ$ the refiner improves SSIM over the ensemble, from $0.8767$ to $0.8780$ on a held-out reproduction of the official scorer and from $0.8555$ to $0.8572$ on the official validation leaderboard, with essentially no change in MSE. The gain is small but consistent, improving $62.6\%$ of the held-out cases with a signed-rank $p=2.2\times10^{-7}$, whereas over-weighting the structural term reverses it. Two ablations bound the effect. Adding any third model to the two-model ensemble degrades it, and classical unsharp masking fails to improve SSIM at any strength (best $0.8765$ against $0.8767$), so the gain reflects learned rather than indiscriminate sharpening. The result is a cheap, reproducible post-processing stage that improves an already strong ensemble without any large-scale retraining.
Tomas Guija-Valiente, Blanca Rodriguez-Gonzalez, Norberto Malpica +1cs.CV cs.AI cs.LG
Medical image inpainting has the potential to improve automated brain MRI analysis by reconstructing healthy tissue within pathological regions. We introduce RARF, a task-agnostic region-aware rectified flow framework for masked data generation. We instantiate the framework for 3D brain MRI inpainting as our submission to the BraTS Inpainting Challenge 2026. RARF restricts the stochastic interpolation process to the inpainting region, while the observed voxels remain fixed and provide patient-specific anatomical context. A three-dimensional neural network receives the partially voided image, with Gaussian noise filling the missing region, together with the inpainting mask and the corresponding timestep. The model is trained using masked flow-matching and reconstruction-consistency objectives, combined with mask-aware preprocessing and data augmentation. During inference, the learned velocity field transports the initial noise toward a plausible reconstruction of the missing tissue, which is then combined with the unchanged observed anatomy. Experiments under the BraTS evaluation protocol show that the proposed approach produces competitive reconstructions while maintaining anatomical consistency. Source code is available at: https://github.com/TomasGuija/rarf.
Khawaja Murad ul Hassan, Ruqiyya Adil, Adil Qayyum +4cs.CV
A capable brain-MRI report generator can still be, in effect, diagnostically silent. When a multi-chain chain-of-thought (CoT) reporter built on a medical Mistral-7B backbone is evaluated on held-out cohorts, it names most meningiomas and almost all metastases "glioma" (diagnosis recall 0.44/0.07). Yet the answer is not absent from the model: a supervised linear probe applied to its frozen segmentation features recovers the three tumour cohorts at 0.82 macro-F$_1$ (5-fold cross-validation; chance $\approx$0.33). We introduce NeuroFusion, an assistive reporter that surfaces this latent signal rather than overriding it: discriminative field-classifier heads over per-lesion features condition a fast, single-pass draft-then-review decoder on their committed outputs. Built on the identical Mistral backbone, this restores the diagnosis (meningioma 0.92, metastasis 0.75) and wins 8 of 9 prose-content comparisons across three held-out cohorts (RaTEScore, RadGraph-F$_1$, GREEN; Holm-corrected paired BCa), with no significant loss on the ninth, at 5-6x lower latency ($\approx$80 vs. 457 s/case). A controlled negative result sharpens the mechanism: a learned diagnosis pin that overrides the decoder instead of merely informing it collapses out-of-distribution metastasis recall to 0.03. Grammar-constrained decoding keeps 92.3% of records schema-valid, making every sentence entailment-checkable (7.5% contradicted vs. 36.8% for the direct baseline). In a blinded nine-case pilot, two board-certified neurologists independently rated NeuroFusion highest in every tumour type, the only system with zero critical errors, and gave it the top-rated sign-off in eight of nine cases (six outright, two ties).
Neuroradiologists rarely read a brain MRI in isolation, yet automated brain-MRI report generation has been built almost entirely for single studies. Temporal analysis has been explored on chest radiography and chest CT, but to our knowledge, longitudinal reporting for brain MRI, where interval change is often subtle and spatially distributed, remains unaddressed. We present BrainDiff, the first longitudinal vision-language system for brain MRI. BrainDiff outperforms both frontier general-purpose and single-study neuroimaging models on the same patient pairs. Moreover, BrainDiff retains 91% of internal RadGraph-XL entity+relation F1 (rg_er) on an external, cross-hospital cohort. Beyond the system, we contribute three analyses. First, we identify two independent grounding levers: a counterfactual objective with prior-report dropout, which increases measured image reliance by ~47%, and a staged curriculum. Together, these interventions raise image reliance 2.5-fold from the baseline. Second, we provide a factorial over prior-report availability and image identity, isolating a visual contribution of +0.0387 rg_er, which grows when the prior report is withheld. Third, a cheap change-decodability test for candidate backbones shows that interval change is decodable far more weakly than single-study pathology (0.60 vs. 0.77 AUROC). Code is publicly available at https://github.com/jhuldr/BrainDiff.
Full-image objectives in brain magnetic resonance imaging (MRI) super-resolution (SR) can underweight tissue-transition regions affected by the partial-volume effect (PVE), as these regions occupy only a small fraction of the image. Binary boundaries also do not capture the continuous mixture of cerebrospinal fluid, gray matter, and white matter within a voxel. We propose Anatomy-Guided Gaussian-Parameter Warping with PVE-Balanced Reconstruction (AGW-PBR), which combines a low-resolution (LR)-only reconstruction backbone with a training-time objective that emphasizes tissue transitions. The backbone integrates LR-derived Sobel guidance, soft latent-basis assignment, and bounded grid-anchored residual warping. Fixed, quality-controlled tissue fractions derived from registered T1/T2/PD IXI images are converted into tissue-mixture entropy, which defines mean-normalized reconstruction weights within validated PVE support. These sidecars are used only during training, and inference requires only the LR image. AGW-PBR is evaluated on T2-weighted IXI images at 2x, 4x, and 6x using three seeds and subject-level paired analyses. At 4x, test-only SynthSeg masks independently assess reconstruction in tissue-interface and non-interface regions. Targeted ablations examine valid-support supervision, spatially aligned entropy weighting, and soft latent assignment. The AGW-backbone is also trained from scratch on fastMRI at 4x without PVE supervision. AGW-PBR improves full-image reconstruction across the tested IXI scales and regional fidelity at 4x, while the PVE-free backbone retains strong performance on fastMRI. These findings support tissue-mixture entropy weighting for partial-volume-aware brain MRI SR.
3D brain MRI generation has made significant advances in medical imaging, simulation, and controllable anatomical analysis. However, existing generative models typically synthesize 3D volumes monolithically, often overlooking regional anatomical structures and limiting local controllability. To address these limitations, we introduce AnaDiffusion, an anatomically compositional latent diffusion framework that factorizes the generation process into distinct, anatomically meaningful regions, followed by part-to-whole assembly and global refinement. Our approach first trains part diffusion models to capture local structural priors. We then inject an assembled anatomical composite of the parts into the whole-brain latent representation and continue denoising. This mechanism enables the model to resolve global context while preserving the injected anatomy. As a result, AnaDiffusion produces both explicit part assets and a globally coherent volume, thereby enabling controllable part editing without requiring subject-specific dense segmentation maps at inference time while maintaining consistent part-to-whole brain structure. On the subject-disjoint ADNI test split, AnaDiffusion achieves the lowest FID across the whole brain, left and right hemispheres, cerebellar-brainstem complex, and seam regions. It also achieves the best cerebellar and second-best ventricular and brainstem absolute Cohen's d values among the evaluated methods. In localized editing experiments, paired MS-SSIM demonstrates high target transfer and off-target preservation, supporting controllable part replacement with minimal unintended anatomical alterations.
Radiology report generation has matured almost entirely on 2D chest radiographs, where the default route to better reports is a larger backbone or a pre-training one on medical data. We revisit that assumption on 3D multi-sequence brain MRI, a volumetric multi-disease regime, and find that the model is not the lever. Zero-shot medical and radiology vision-language models transfer poorly to brain MRI, with chest radiograph specialists failing most conspicuously, and five backbones fine-tuned identically across three model families and an order of magnitude in scale differ only marginally. What determines the quality of the report is the information injected into the prompt. We delegate perception to upstream 3D segmentation and classification, serialize their outputs into a structured fact sentence, and prompt a LoRA-adapted vision-language model with it; we call this \textbf{PerFact}. In a controlled study that fixes the backbone, data split, target reports, and adaptation while varying only the injected grounding, perception-derived facts outperform retrieved prior reports, retrieval becomes redundant once facts are present, and end-to-end predicted facts remain effective without any ground-truth annotation at inference. The residual gap between predicted and oracle facts is explained by the granularity of the facts rather than by the generator. Closed-ended visual question answering comes at no measurable cost to report quality, though the grounding source has little effect on it. On 3D brain MRI, grounding information, not model choice, is the dominant controllable factor in report quality.
Vishnu M. Bashyam, Guray Erus, Junhao Wen +29cs.CV
Deep learning models for neuroimaging have largely been developed for individual tasks, limiting knowledge transfer across applications. Here we introduce GenFAR, a modular deep learning framework that learns general, clinically informed features from brain MRIs. We trained this modular architecture on 49,246 individuals across 11 cohorts, using 17 diverse classification and regression tasks spanning cognition, clinical, diagnosis, demographics, and biomarkers. This yields aggregated, focused feature sets that capture rich, clinically- and biologically-relevant brain representations. We developed a sequential learning approach where tasks progressively build on previously learned representations. Through an analysis of 5,000 task sequences, we identified an optimal sequence length of six tasks and introduced a Donor Score metric to quantify each task's contribution to downstream performance. This analysis revealed five consistently strong donor tasks (Age, AD/MCI, MMSE, Hypertension, Hyperlipidemia) that formed the base of our sequential model. We demonstrated the utility of our learned representation, in various tasks beyond those included in the training set, to serve as the foundation for specialized secondary predictors. We further showed that using the learned feature representation can substantially increase the sample efficiency of secondary deep learning training tasks and models, as well as improve their accuracy.
Frozen foundation-model (FM) embeddings are increasingly used as off-the-shelf brain-MRI representations, on the assumption that they capture anatomy. We audit what they actually encode and find that acquisition site is a large, intrinsic component of the representation. Across two independent cohorts (ABIDE-I, ABIDE-II), three frozen 3-D encoders (brain-pretrained, CT-pretrained, and randomly initialized), and every network depth, site is linearly decodable at roughly 0.9 balanced accuracy at deep layers, exceeding the decodability of every clinical or demographic variable (sex, age, autism diagnosis) at every layer. The effect is intrinsic rather than learned: a randomly initialized encoder is already a ~0.9 site classifier on both cohorts and across three architecture families (Swin, ViT, ResNet), and site is decodable at ~0.95 directly from the raw downsampled image with no encoder, so the fingerprint reflects low-level image statistics that any encoder preserves rather than a product of pretraining. Residualizing measured population covariates leaves site decodability essentially unchanged, indicating an acquisition- rather than population-driven effect. A nonlinear probe matches the linear one, so the fingerprint is fully linearly accessible. The site subspace is removable post hoc by iterative null-space projection or ComBat (site decodability 0.94 -> 0.07/0.00), and is a site-attribution concern for shared or federated embeddings; but for dense segmentation this removal is not free, because site and anatomy occupy an entangled linear subspace (a matched-rank random-direction projection is Dice-neutral, whereas removing the site subspace is destructive). We recommend site-audited use of frozen brain-MRI FMs and release an open audit toolkit.
Patient motion remains a source of image degradation in brain MRI, leading to signal loss, blurring, and geometric distortion that compromise quantitative analysis. Existing deep learning methods for motion correction typically rely on paired clean-corrupted data or k-space acquisitions, which are rarely available in clinical settings. We propose SSRL-MAR, a motion artifact-aware unpaired representation learning framework for motion artifact reduction that requires neither paired training data nor explicit motion labels. SSRL-MAR employed a three-stage training strategy: (1) contrastive learning on 3D patches to extract motion representations by contrasting clean and synthetically corrupted images, (2) a motion artifact-aware synthesis network to generate motion artifacts from clean scans, and (3) a motion artifact-aware generator to restore clean volumes using the learned degrader for self-supervised supervision. On in-silico dataset, SSRL-MAR achieved PSNR 23.81dB, SSIM 91.55%, and NMSE 0.79%. On in-vivo MR-ART dataset, the pretrained model reduced motion distortion, and unsupervised domain adaptation further improved anatomical fidelity. Against a source-only supervised model trained on the same simulated pairs, SSRL-MAR improved PSNR by up to 2.0 dB on MR-ART after unsupervised domain adaptation, and remained within 0.25-0.47 dB of an oracle supervised model that requires real paired data unavailable in practice. At the milder motion level, volumetric error in structures such as the corpus callosum and ventricular system decreased by more than 50%, confirming improved neuroanatomical consistency. These results indicate that SSRL-MAR provides a robust and scalable image-domain solution for 3D brain MRI motion correction, enabling reliable structural quantification in large-scale neuroimaging studies without requiring prospectively acquired pairs or acquisition-specific calibration.
Michail Mamalakis, Carmen Jimenez-Mesa, Yonghao Li +8cs.CV cs.LG
Brain magnetic resonance imaging (MRI) is central to neuroscience and clinical assessment, but models are commonly developed for individual diseases, populations or imaging protocols. Foundation models promise more general representations, yet they are usually pretrained once and can lose earlier capabilities when updated with new data. Here we show that Alcmaeon, a three-dimensional brain MRI foundation model pretrained without manual labels on more than 425,000 volumes and derived imaging maps, can be expanded sequentially across clinical domains. Alcmaeon combines volumetric encoding and latent diffusion generation with Graph-Blueprint Pruning (GBP), which protects network modules important to earlier domains while leaving the remaining capacity trainable. Across expansion from healthy ageing and neurodegeneration to developmental, psychiatric and tumour imaging, GBP showed less forgetting than sequential adaptation and elastic weight consolidation across voxel-level reconstruction measures, with its largest advantage after adaptation to tumour imaging. The blueprints provided an inspectable record of how model capacity was protected and reused. Representations from different model levels supported image synthesis, disease classification, survival modelling and postoperative prediction, although no single representation was optimal for every task. These findings provide a route towards brain MRI foundation models that can grow with emerging data while retaining earlier capabilities.
Ali Khoramfar, Mohammad Javad Dousti, Alireza Mohamadian +1cs.CV cs.CL
Standard accuracy metrics for VLMs often mask significant reliability failures in sensitive domains. In this work, we utilize a histopathology-validated brain MRI dataset to systematically assess the diagnostic robustness of four VLM families under evidence-preserving perturbations. By reordering anatomical slices and swapping target label positions, we evaluate whether models maintain consistent predictions when clinical evidence remains invariant. Our results reveal significant vulnerabilities in presentation-order stability, with models exhibiting prediction flips in up to 48.9% of cases under simple sequence reversals. We further identify a textual selection bias, where label reordering triggers inconsistent diagnoses in up to 67.8% of cases despite identical visual inputs. Negative-control tests further reveal diagnostic overcommitment: models generate categorical diagnoses in up to 76.1% of cases after expert-annotated lesion slices are removed. These results demonstrate that high accuracy can overestimate clinical reliability, masking sensitivity to sequential presentation and textual framing that is not captured by aggregate accuracy. Our findings highlight the necessity of stability-based metrics for the deployment of VLMs in safety-critical clinical applications. Our evaluation data and code will be made public upon acceptance.
Kaouther Mouheb, Gonzalo Esteban Mosquera Rojas, Juancito van Leeuwen +2cs.CV
Medical foundation models (FMs) are increasingly used for brain MRI analysis. However, their evaluation remains dominated by high-resource datasets, leaving generalization to African cohorts underexplored. We assess whether FMs generalize equally to African and non-African brain MRI data across two tasks: dementia classification using a Nigerian dataset and brain tumor segmentation using BraTS-Africa. We evaluate two generalist FMs (BrainIAC, 3DINO) and two segmentation-specific FMs (MedSAM2, Medical-SAM2) against a from-scratch baseline. For classification, FMs provide limited gains (highest ROC-AUC of 0.86 with BrainIAC), whereas for segmentation they consistently improve performance, reaching up to 0.86 Dice with MedSAM2. Performance differences between African and non-African cohorts are inconsistent and appear more related to dataset size than data origin. These results suggest that FMs do not exhibit an inherent bias against African cohorts, and highlight the limited availability and diversity of African neuroimaging datasets as the main barrier to robust evaluation and deployment.
Predicting future structural MRI of a brain is challenging because longitudinal changes are often subtle and confined to specific anatomical regions, while most subject-specific brain structure remains stable over time. An effective model should therefore preserve global brain structural consistency while remaining sensitive to fine-grained disease progression. Existing latent-space-based methods improve computational efficiency, but suffer from information loss during their compression-reconstruction procedure. In contrast, direct voxel-space methods avoid latent reconstruction but commonly use a unified prediction pathway to model brain structure and progression-related changes. Subtle local changes may therefore be overshadowed by the dominant stable brain structure. To address these challenges, we propose ProgFormer, a hierarchical voxel-space Diffusion Transformer for longitudinal brain MRI prediction. ProgFormer uses a coarse pathway to perform the primary volumetric prediction from 3D patch tokens. This pathway models overall brain structure and longitudinal context. The fine pathway then uses the coarse representations as spatio-temporal grounding for voxel-level refinement within individual patches. The two pathways jointly estimate a velocity field directly in voxel space through conditional flow matching, enabling end-to-end prediction without a separately learned image autoencoder. The predicted future scan is then generated from Gaussian noise by integrating the estimated velocity field over a sequence of Euler steps. Extensive experimental results on three widely used benchmarks, ADNI, AIBL, and OASIS, under both pairwise and trajectory settings demonstrate favourable performance compared against several state-of-the-art methods.
Qinghui Liu, Jon André Ottesen, Atle Bjørnerud +1cs.CV cs.LG
Rigorous dataset partitioning is a foundational, yet frequently overlooked, prerequisite for reliable deep learning in longitudinal medical imaging. Naively shuffling small clinical cohorts routinely introduces covariate shifts and temporal sampling imbalances across training, validation, and test subsets, exposing downstream models to out-of-distribution evaluation. We address this vulnerability with an auditable Tripartite Dataset Analytics Framework that systematically characterizes spatial grid integrity, multi-parametric intensity fingerprints, and longitudinal temporal trajectories, quantifying the heavy-tailed feature dispersion and irregular, episodic sampling intervals typical of real-world clinical cohorts. Building on this characterization, we formalize an unsupervised spatio-temporal cohort-balancing standard operating procedure (SOP) that combines elbow-optimized K-means clustering over a standardized, six-dimensional joint intensity-temporal feature space with intra-cluster proportionate stratified sampling. On a longitudinal, contrast-enhanced $T1$-weighted brain MRI cohort (N=149), the protocol reduces the maximum cross-subset intensity bias from 34.1% under conventional random shuffling to under 2.1%, while aligning longitudinal follow-up intervals closely around the population mean. Monte Carlo stress testing across ten random seeds and three split configurations confirms that this alignment remains tightly bounded, in clear contrast to the substantial variability of random partitioning. The resulting protocol offers a reproducible, generalizable procedure for cohort engineering in variable-length longitudinal clinical imaging workflows.
Rick Wilming, Irem Ozseker, Luca Matteo Cornils +4cs.CV cs.LG
Validating Explainable Artificial Intelligence (XAI) methods in medical imaging requires ground-truth data with known locations of informative features. However, current approaches rely on expert annotations, which are prone to labeling errors, or on hand-crafted artificial perturbations superimposed onto healthy images to mimic lesions or malignant features, which lack clinical realism. We present Local Label-Informed Feature Transfer (LLIFT), a framework for generating semi-synthetic brain magnetic resonance images with realistic lesions placed in user-controlled regions, which does not require pixel-level lesion annotations during training. We implement LLIFT with two generative paradigms: LLIFT-GAN, a custom GAN that learns pathological features from binary class labels alone, and LLIFT-DM, a diffusion-based inpainting pipeline conditioned on bounding-box masks via ControlNet. Both approaches are evaluated on brain magnetic resonance imaging data derived from the Human Connectome Project. In evaluations, both achieve Fréchet Inception Distance scores, with respect to the real pathological distribution, that are comparable to the inter-class reference between healthy and pathological images in the given dataset. Furthermore, qualitative inspection confirms the realism of lesion structures. The resulting benchmark datasets provide spatially controlled ground truth data for evaluating XAI methods in medical imaging.
Moona Mazher, Abdul Qayyum, Steven A. Niederer +1cs.CV cs.AI
Foundation models pretrained using self-supervised learning have transformed computer vision by learning transferable representations from large-scale unlabeled data. However, existing foundation models for neuroimaging remain limited by task-specific training, slice-based learning strategies, or relatively small pretraining datasets, restricting their generalizability across diverse brain MRI applications. In this work, we present BrainNext, a general-purpose self-supervised foundation model for volumetric brain MRI analysis. BrainNext combines masked autoencoder (MAE) pretraining with a native three-dimensional Bi-Directional xLSTM-UNet architecture to learn rich anatomical representations from 60,551 unlabeled brain MRI examinations spanning multiple MRI modalities. The pretrained model is subsequently adapted to downstream tasks through lightweight task-specific fine-tuning. We evaluate BrainNext on the Foundation Models for Medical Imaging (FOMO) 2025 Method Track, encompassing classification, segmentation, and brain-age estimation, where it achieved second place overall and ranked first in the meningioma segmentation task on the official FOMO 2025 challenge leaderboard, demonstrating strong transferability across heterogeneous neuroimaging tasks. These results highlight the potential of large-scale self-supervised pretraining to learn robust and transferable volumetric representations, establishing BrainNext as a scalable foundation model for diverse brain MRI applications.
Sara Ketabi, Matthias W. Wagner, Cynthia Hawkins +3cs.LG q-bio.QM
Multimodal Contrastive Learning (CL) has shown significant performance in aligning representations across various data modalities and improving downstream tasks, especially in healthcare. It works by minimizing the distance between matched (positive) data modalities, while maximizing the distance between mismatched (negative) samples. Traditional CL frameworks typically assume instance-based correspondence within data batches, treating all non-paired samples as negatives. However, this assumption often fails in medical settings, where samples may share high-level semantic attributes, leading to false negatives that degrade representation quality. In this paper, we propose Multimodal Semantic-Aware Contrastive Learning (MseaCL), a CL framework trained on a pediatric cohort of 3D brain magnetic resonance imaging (MRI) scans and radiology reports. The goal of this framework is to mitigate the impact of semantically similar false negative samples by incorporating semantic similarity between radiology reports, as a guiding signal during the learning process. Our results indicate that applying this framework as a pretraining stage can achieve notable improvements in downstream tasks, e.g., at least a 22.6\% increase in the area under the receiver operating characteristic curve (AUC) of pediatric brain tumor molecular classification, demonstrating its potential for more robust and semantically aligned multimodal representations in clinical applications.
Foundation models provide powerful representations for brain MRI analysis, but their predictions remain difficult to interpret in anatomically meaningful terms. Clinical assessment of brain MRI is commonly organized around anatomically defined structures and regional abnormalities, whereas conventional explanation methods typically produce voxel- or patch-level importance maps that do not explicitly quantify the contributions of individual brain regions. To address this mismatch, we propose RegionFM, an interpretable framework that integrates anatomical segmentation with brain MRI foundation-model embeddings. RegionFM first divides each MRI scan into anatomical regions and constructs a separate MRI volume for each region. A frozen foundation model then encodes each region into an embedding, and a region-additive logistic model combines these embeddings such that every anatomical region contributes an explicit scalar term to the final prediction. This formulation supports both subject-level and cohort-level analyses of regional contributions. We evaluate RegionFM on cognitive-impairment classification using embeddings from multiple pretrained brain MRI foundation models. The results show that RegionFM maintains performance comparable to less interpretable fine-tuning approaches while providing anatomically grounded explanations. Randomized embedding ablations yield near-chance performance, indicating that the predictions rely on meaningful structure captured by the foundation-model embeddings rather than simple feature statistics. Overall, RegionFM better aligns model explanations with anatomy-based clinical reasoning while maintaining competitive predictive performance.
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.
Medical image registration benefits significantly from deep learning, yet existing approaches often lack physical explainability and fine-grained deformation control. Motivated by Demons algorithms, we propose a novel DrivenMorph framework that bridges attention mechanisms with variational image registration by incorporating difference modeling as a physically inspired inductive bias. The resulting driving force, computed from local differences in the latent feature space, provides explicit semantic guidance throughout the registration process. It directly drives the registration process through a neural Demons layer that simulates force-displacement interactions to generate smooth and anatomically consistent deformation. Unlike previous methods, our approach not only integrates traditional registration principles with popular deep networks, providing an explainable and efficient solution for learning-based medical image registration, but also separates difference modeling from deformation, improving modularity and explainability. Extensive experiments on multiple 3D brain MRI datasets demonstrate superior performance over state of-the-art learning-based and optimization-based methods. Furthermore, visualizations and statistical analyses confirm that the learned driving force aligns closely with actual deformation patterns, supporting its explanatory value.
We study a quantum autoencoder (QAE) for compression-driven anomaly detection in brain MRI data. The approach leverages angle encoding to map image patches into quantum states, followed by a variational encoder-decoder architecture trained to discard information via auxiliary trash qubits. Anomaly scores reflect the degree to which inputs resist compression relative to normal data, with higher scores corresponding to deviations from the learned normal manifold. Evaluated on publicly available brain MRI DICOM datasets, the method achieves a slice-level ROC-AUC of approximately 0.95 and a patch-level ROC-AUC of approximately 0.813, outperforming classical autoencoder and PCA baselines. Analysis of the learned parameters reveals a pronounced encoder-decoder asymmetry, where effective anomaly detection arises from structured information compression within the encoder rather than increased parameter magnitude or decoder expressivity. This results in a controlled compression-reconstruction trade-off with a clear operating regime that supports principled threshold selection. Qualitative evaluation further shows that the QAE produces spatially localized anomaly heatmaps aligned with tumorous regions. The results, supported by promising baseline performances, demonstrate that quantum autoencoders provide an interpretable and controllable mechanism for anomaly detection based on incompressibility with respect to a learned latent representation. This work highlights the potential of quantum autoencoders as a principled tool for studying compression dynamics in quantum machine learning, with promising implications for decision support in medical imaging workflows.
Medical vision-language models typically generate diagnoses through single-pass inference without indicating which image regions support their conclusions. This lack of spatial grounding limits clinical utility: outputs cannot be audited, and models may hallucinate findings on normal scans. We present BrReMark (Brain Rethink via ROI Marking), a framework that introduces explicit region marking into brain MRI diagnosis. The model first generates hypotheses about potential abnormalities and grounds them through explicit bounding box marking, then verifies conclusions by re-examining the marked evidence. Training combines supervised fine-tuning on structured reasoning trajectories with reinforcement learning using a composite reward over localization accuracy and diagnostic reasoning. Furthermore, we integrate a domain randomization-based pathology synthesis augmentation strategy to improve the model's generalizability to out-of-distribution (OOD) data. On internal benchmark, BrReMark improves mAP50 from 0.74% to 37.54% compared to the base model, while achieving 21.57% Clinical F1 and 45.26% diagnostic accuracy. On NOVA OOD benchmark, it also achieves competitive overall performance with a 45.7% reduction in false positives compared to the state-of-the-art, indicating reduced hallucination on rare pathologies. These findings suggest that explicit hypothesis-verification grounding is a practical path toward trustworthy open-ended brain MRI diagnosis across both in-distribution and OOD settings.
Max Van Puyvelde, Ibrahim Gulluk, Wim Van Criekinge +1cs.AI cs.CV cs.LG
Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.
Multi-contrast brain MRI provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-contrast images. While current approaches excel in image synthesis, they often struggle to synthesize critical tumor regions and exploit contextual information in multi-contrast brain MRI effectively. To address this issue, we propose a synthesis-centric, segmentation-assisted closed-loop framework with retrieval augmentation synthesis. Our method overall takes a generative adversarial architecture, which aims to synthesize missing contrasts from any combination of available ones with a single model. To explicitly capture tumor semantics and focus synthesis on tumor regions, we add an auxiliary segmentation branch that predicts tumor masks and feeds them back as semantic conditioning in synthesis branch, thereby learning tumor-aware representations in the model and improving synthesis fidelity. Furthermore, we propose a dual-bank retrieval augmentation strategy. It dynamically queries two external knowledge bases, namely a tumor masks memory bank for crucial tumor context and cross-image contrast feature memory bank for global style information, to augment synthesis. Verified on two public multi-contrast magnetic resonance brain datasets: BraTs2020 and UCSF-BMSR, the proposed method is effective in handling medical brain images synthesis tasks and shows superior performance compared to previous methods. Code is available at:https://github.com/iBizzard/SSCF.git
Yizhou Wu, Shansong Wang, Yuheng Li +5cs.LG cs.AI cs.CV
Brain MRI underpins a wide range of neuroscientific and clinical applications, yet most learning-based methods remain task-specific and require substantial labeled data. Here we show that a single self-supervised representation can generalize across heterogeneous brain MRI endpoints. We trained BrainDINO, a self-distilled foundation model, on approximately 6.6 million unlabeled axial slices from 20 datasets encompassing broad variation in population, disease, and acquisition setting. Using a frozen encoder with lightweight task heads, BrainDINO supported transfer across tumor segmentation, neurodegenerative and neurodevelopmental conditions classification, brain age estimation, post-stroke temporal prediction, molecular status prediction, MRI sequence classification, and survival modeling. Across tasks and supervision regimes, BrainDINO consistently equaled or exceeded natural-image and MRI-specific self-supervised baselines, with particularly strong advantages under label scarcity. Representation analyses further showed anatomically organized and pathology-sensitive feature structure in the absence of task-specific supervision. Our findings indicate that large-scale slice-wise self-supervised learning can yield a unified brain MRI representation that supports diverse neuroimaging tasks without volumetric pretraining or full-network fine-tuning, establishing a scalable foundation for robust and data-efficient brain imaging analysis.