Semi-supervised learning has shown great potential for reducing annotation costs in medical image segmentation. However, most existing methods mainly exploit unlabeled data through prediction-level consistency, while the reliability of internal feature representations is often overlooked. In medical images, target-related structural cues are easily entangled with unstable appearance variations, which may lead to unreliable pseudo labels and error accumulation during training. To address these issues, we propose SAUF-Net, a Structure--Appearance Representation Learning with Uncertainty Feedback Network for semi-supervised medical image segmentation. SAUF-Net uses the Structure--Appearance Decomposition Module (SADM) to separate bottleneck features into structural and appearance representations. The Disentangled Guidance Module (DGM) injects these representations into the decoding process to enhance structure-aware segmentation. Meanwhile, the Auxiliary Decoder produces branch-specific predictions for reliability estimation and a fused prediction for appearance-swapped consistency. Furthermore, we introduce an Appearance-Swapped Consistency branch to encourage structural representations to remain stable under appearance variations. We also introduce a reliability-map-guided dual-head discriminator with a Validity Head and an Uncertainty Head to provide feature-level uncertainty feedback. Extensive experiments on ISIC-2016 and Kvasir-SEG demonstrate that SAUF-Net outperforms state-of-the-art semi-supervised methods, especially under low-label settings.
In computational pathology (CPath), developing omni-modal self-supervised learning (SSL) models that integrate histology, genomics, and clinical reports enables transferable representation learning for whole slide images (WSIs). Existing approaches implicitly force heterogeneous modalities into a uniform latent space by contrastive alignment, causing modality collapse where unique, synergistic diagnostic signals (termed as $\mathrmΦ$) are discarded in favor of trivial redundancy. We hypothesize that the strongest task-agnostic SSL training signal stems from distilling the synergistic interactions over merely aligning shared redundancy. To this end, we introduce \textsc{$\mathrmΦ$-Omni}, a synergistic information disentanglement framework grounded in Partial Information Decomposition (PID) theory for slide representation learning. Unlike standard contrastive approaches, \textsc{$\mathrmΦ$-Omni} employs a Synergistic Information Bottleneck (SIB) regulated by the proposed $\mathrmΦ\text{ID}$ objective, which explicitly suppresses marginal redundancy while maximizing irreducible synergy, thereby distilling high-order cross-modal interactions. Following pretraining on breast ($n$=1031) and lung ($n$=919) cohorts, \textsc{$\mathrmΦ$-Omni} demonstrates superior few-shot performance across five independent external datasets spanning eight tasks compared to supervised and SSL baselines. Source code is available here.
Dense self-supervised learning (SSL) is a powerful paradigm for learning without annotations the local descriptors required to solve dense medical imaging tasks. We present Pix2Rep-v2, a framework for SSL of pixel- and voxel-level representations suitable for few-shot downstream applications. Pix2Rep-v2 addresses the main challenges of dense SSL by leveraging a redundancy reduction objective at the pixel-level with a principle of equivariance of dense representations, that scales efficiently to 3D or wide field-of-view applications. We evaluate our method on four datasets, across multiple tasks, multiple modalities and anatomical structures using multiple backbones in 2D and 3D, and under various data regimes. As an alternative to linear probing or full fine-tuning on the downstream task, we also propose an in-context variant, without downstream training, based on a dense prototype approach. Pix2Rep-v2 shows substantially higher data-efficiency in few-shot scenarios compared to fully supervised baselines, and is competitive with the state-of-the-art e.g., +9.3 Dice points in one-shot segmentation on the M&Ms-2 dataset. Our code and pre-trained models are publicly available at https://github.com/BioMedTP/pix2rep-v2.
Wearable EEG systems may expose sensitive information beyond their intended health function, creating substantial risks to neuroprivacy. In this work, we show that commonly used EEG features can reveal participant identity and demographic attributes in addition to supporting the intended cognitive task. Wearable EEG is increasingly being explored for cognitive monitoring, neurological assessment, and longitudinal digital-health applications, yet many systems assume that transmitting compact spectral or spatial features instead of raw EEG provides sufficient privacy protection. Using EEGMAT as a motivating case study, we find that compact EEG features achieve a balanced accuracy of 0.788 for cognitive-state classification while enabling gender, age, and subject-identity inference with balanced accuracies of 0.858, 0.789, and 0.692, respectively. We further show that privacy-aware representation learning preserves task performance at 0.781 while reducing these inference accuracies to 0.563, 0.467, and 0.206. These findings motivate purpose-limited representations and explicit privacy auditing in wearable neurohealth systems.
Peptide-protein affinity models are often evaluated with a single data split, obscuring whether they interpolate among measurements for observed targets or generalize across peptide or target shifts. We integrated three sources of quantitative peptide-protein binding data to obtain 11,349 deduplicated pairs and benchmarked ten peptide representations, ESM-2 protein embeddings, and six regressors under peptide-similarity, within-target, and leave-target-out partitions. Across 60 matched representation-regressor configurations, mean test Spearman correlations were 0.462, 0.669, and 0.530, respectively. The top configuration shifted from ECFP-16 count fingerprints with random forest in the first two settings to HELM-BERT with Extra Trees when exact target sequences were excluded. Representation-rank correlations ranged from -0.042 to 0.624 across partitions, whereas regressor-rank correlations ranged from 0.771 to 0.943. Learning curves showed that representation differences were largest with limited supervision and narrowed as training data increased. PeptideCLM-2 adaptation and simple element-wise interaction features provided no consistent gain over a frozen encoder and direct concatenation under the tested protocols. These conclusions are specific to a dataset that pools transformed Kd, Ki, and IC50 measurements and to target exclusion at the exact-sequence level. Peptide-protein affinity benchmarks should therefore align data partitions with the intended use and jointly assess the effects of data scale, molecular representation, and downstream learner.
Cardiovascular risk prediction remains limited by incomplete clinical data and imaging biomarkers that reduce computed tomography (CT) to a small number of handcrafted features. We developed CARDINAL (Cardiovascular Assessment via Representation learning from Deep Imaging with Nested Anatomical Latent embeddings), a clinically grounded framework that learns compact representations from routine non-contrast cardiac CT for major adverse cardiovascular event (MACE) prediction. In 17,659 patients, CARDINAL was evaluated for 1-, 3-, 5-, and 10-year MACE prediction against American Heart Association (AHA) pooled cohort equations (PCE), AHA predicting risk of cardiovascular disease events (PREVENT), coronary artery calcium (CAC), segmentation-derived CT biomarkers, and 70-feature structural radiomics. Gains were largest at longer horizons. At 10 years, CARDINAL (joint) achieved an area under the receiver operating characteristic curve (AUROC) of 0.866 $\pm$ 0.020 and an area under the precision-recall curve (AUPRC) of 0.890 $\pm$ 0.015, compared with an AUROC of 0.826 $\pm$ 0.023 and an AUPRC of 0.826 $\pm$ 0.022 for structural radiomics, the strongest baseline. CARDINAL also achieved the highest survival concordance index (C-index), 0.753 $\pm$ 0.015, and high-versus-low risk-tertile hazard ratio, 10.78 $\pm$ 3.16, with favorable reclassification and exploratory calibration. These findings suggest that non-contrast cardiac CT contains prognostic information beyond conventional risk equations, CAC scoring, and engineered imaging biomarkers.
Medical vision-language models (VLMs) can appear reliable in-domain while failing when acquisition domain, paired supervision, or evaluation protocol changes. We study this failure mode as a representation-level blind spot relevant to epistemic intelligence, without claiming a formal estimator of epistemic uncertainty. Using NIH ChestXray14 and CheXpert, we first isolate source-only cross-dataset visual transfer from unsupervised domain-adaptation diagnostics. Using PadChest and OpenI, we then evaluate multimodal alignment under strict pair-index retrieval and quantify metadata-derived source-proxy information retained in frozen embeddings. Self-supervised visual initialization improves NIH-to-CheXpert transfer over supervised ImageNet initialization in matched ResNet-18 comparisons, whereas adversarial adaptation is useful only in a narrow regime and becomes unstable as adversarial pressure increases. Multimodal exact-pair retrieval remains low under external OpenI stress testing, and source-proxy information remains recoverable from learned representations. Qualitative nearest-neighbor and Grad-CAM analyses show clinically plausible cross-dataset structure and thoracic attention patterns in many cases, while device-heavy and false-positive cases remain ambiguous. Auxiliary architecture checks are task-dependent and do not support a universal backbone ranking. Overall, the study shows that apparent competence under a single protocol can conceal transfer, alignment, and shortcut-related failure modes, motivating stress-tested evaluation of medical VLMs under distribution shift.
Spatially resolved biology requires representations that preserve biological neighborhood structure rather than only exact cross-modal correspondences. Existing histology--transcriptomics objectives can emphasize instance-level matching even when non-paired spots share molecular or spatial context. We introduce BioKERN, a multimodal spatial representation-learning framework that incorporates biological structure as an explicit, learnable inductive bias. BioKERN constructs a training-time biological kernel by combining transcriptomic similarity and spatial proximity, then uses it to provide graded neighborhood supervision and regularize embedding geometry. Evaluation uses a fixed, model-independent biological neighborhood definition shared by all methods. Across Mouse Brain Visium and Human Liver GSE240429, BioKERN consistently improves biological-neighborhood retrieval over BLEEP in both single- and multi-scale settings. Controlled shared-architecture experiments show that most of the improvement arises from biological-kernel regularization rather than increased model capacity. These results support explicit biological geometry as an interpretable inductive bias for multimodal learning in spatial biology.
We present a dynamical-systems based model for resting-state functional magnetic resonance imaging (rs-fMRI), trained on a dataset of roughly 40K rs-fMRI sequences covering a wide variety of public and available-by-permission datasets. While most existing proposals use transformer backbones, we utilize multi-resolution temporal modeling of the dynamics across parcellated brain regions. We show that MnemoDyn is compute efficient and generalizes very well across diverse populations and scanning protocols. When benchmarked against current state-of-the-art transformer-based approaches, MnemoDyn consistently delivers superior reconstruction quality. Overall, we find that with such large-scale pre-training on (non-proprietary) rs-fMRI datasets, we get a highly performant model for various downstream tasks. Our results also provide evidence of the efficacy of the model on small sample size studies which has implications for neuroimaging studies at large where resting state fMRI is a commonly acquired imaging modality.
Maryam Rahimimovassagh, Ivan Garibay, Niloofar Yousefiq-bio.QM cs.LG
Protein fitness landscapes contain nonlinear interactions in which mutation effects depend on other residues. We introduce ORBIT, an Order-Resolved Benchmarking of Interaction Transformations framework that separates interaction presence, representation accessibility, and functional recovery. ORBIT first validates Walsh-based diagnostics on synthetic landscapes with known interaction order, then analyzes the experimentally measured GB1 fitness landscape under the FLIP 2-vs-rest setting. We compare ridge regression, a standard MLP, independent tokens, nonlinear independent tokens, and Residual Interaction Tokenization (RIT). Across 20 paired training seeds, the primary two-hidden-layer comparison found no significant architecture differences in FLIP test R^2, third- or fourth-order functional recovery, or final-layer third- or fourth-order accessibility. However, RIT significantly increased pairwise accessibility at the token stage relative to both independent-token controls (Delta A_tok,2 = 0.2468, d_z = 1.67, Holm-adjusted p = 1.14 x 10^-5), without a detectable downstream higher-order advantage. A pre-specified depth/capacity analysis showed that deeper MLPs improved FLIP prediction, third-order functional recovery, and final-layer third-order accessibility; fourth-order accessibility also improved relative to the shallow MLP but remained below zero in absolute held-out R^2. ORBIT therefore reveals representation-level changes hidden by conventional prediction metrics and distinguishes early interaction-aware encoding from higher-order structure constructed by downstream nonlinear capacity.
Full-length RNAs, particularly messenger RNAs, often exceed the context lengths used to pretrain existing RNA foundation models, limiting complete-transcript modeling at single-nucleotide resolution. We present RIBOSPAN, a 1.61-billion-parameter bidirectional RNA foundation model natively pretrained with context lengths up to 10,240 nt. RIBOSPAN combines dense bidirectional self-attention, single-nucleotide tokenization, and attention-isolated sequence packing to enable high-resolution modeling of complete long RNAs. We evaluate the model through nucleotide reconstruction, a controlled long-context representation benchmark, and frozen RNA-type representation analysis. Native 10K pretraining preserves strong reconstruction at 10,240 tokens, while continued pretraining with 40% masking improves recovery under heavy corruption while preserving representation quality. The long-context benchmark further shows that native 10K models maintain strong contextual responsiveness and context-specific representation separation while keeping perturbation-induced representation changes highly localized. Inference-time YaRN scaling recovers much of the contextual organization lost by direct extrapolation of short-context models, but induces substantially greater distal representation diffusion. Frozen-representation evaluations further demonstrate state-of-the-art RNA representation quality, with RIBOSPAN achieving the strongest overall performance across diverse RNA types and retaining a clear advantage on long RNAs. Building on the same backbone, we develop a multidimensionally conditioned discrete-diffusion framework for full-length mRNA generation and redesign, including synonymous-codon diffusion for protein-preserving CDS optimization. Together, RIBOSPAN establishes a powerful long-context foundation for transferable RNA representation learning and full-transcript mRNA design.
Jade Perdereau, Virginie Loison, Kanssa El Ayeb +5cs.LG
General anesthesia offers a rare opportunity to observe the human brain under a standardized, controlled perturbation. Yet intraoperative electroencephalography (EEG) is almost always reduced to a single proprietary depth index, collapsing a rich trajectory into one number and discarding how a brain moves between states. Here we ask whether the geometry of that trajectory, not merely the depth it reaches, carries clinically meaningful information. Using similarity-based self-supervised learning on raw, two-electrode frontal EEG, with no labels, we place each recording within a low-dimensional space in which anesthetic depth becomes one readable axis while the shape of a patient's path encodes additional structure. We validate the representation across two cohorts and two acquisition systems totaling more than 1,000 patients. Depth of anesthesia is predicted accurately (BIS mean absolute error = 3.2, R2 = 0.82), and in the sparse-montage setting our compact ( 68k parameter) model remains competitive with EEG foundation models orders of magnitude larger (4M-157M parameters), indicating that matching the representation to the recording dominates raw scale. The learned space organizes age along its own gradient, independent from depth, without supervision. The same space also aligns with interpretable anesthetic signatures like frontal alpha, slow-delta, and burst suppression, linking this data-driven representation to established neurophysiology. On an independent cohort with longitudinal follow-up, the geometry of the early trajectory separates 30- month cognitive and mortality outcomes complementary to age (AUROC 0.86). These results suggest that the path a brain traces through anesthesia is a label-efficient correlate of latent vulnerability, motivating prospective validation.
Yoshitaka Inoue, Minoh Jeong, Alfred Hero +2q-bio.QM cs.LG
Scarce data and tumor heterogeneity limit patient-level cancer treatment-response prediction. Existing approaches predict response from pretreatment molecular profiles and drug representations, without explicitly modeling the molecular changes expected under treatment. We propose PerturbRx, a treatment-conditioned representation learning framework that learns intervention-induced latent transitions and uses them as patient-drug response features. PerturbRx trains a drug- and dose-conditioned transition predictor from context-matched but cell-unpaired control and treated single-cell populations, then freezes and transfers the predictor to pretreatment patient profiles without requiring post-treatment measurements. The transition is combined with patient and drug representations to predict response. Across TCGA and patient-derived xenograft benchmarks, PerturbRx achieves the strongest aggregate predictive performance among the evaluated methods. These results support perturbation-pretrained latent transitions as useful representations for patient-level drug-response prediction.
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.
Alejandro L. García-Navarro, Carlos Sevilla-Salcedo, Belén Rodríguez-Sánchez +1cs.LG cs.AI
Machine learning models for MALDI-TOF mass spectrometry have shown considerable promise for clinical microbiology tasks such as microbial identification and antimicrobial resistance prediction. However, their deployment across institutions remains limited by domain shift, as acquisition-specific variability often leads models to capture technical artifacts rather than transferable biological information. Existing representation learning approaches primarily address this problem through statistical domain alignment while largely overlooking the biological supervision naturally available in microbiology datasets. We introduce DALMA, a probabilistic representation learning framework that jointly models acquisition-specific variability and biological supervision to learn biologically structured latent representations. By combining domain-specific reconstruction with biologically guided representation learning, DALMA learns transferable representations that generalize across heterogeneous clinical centers without requiring institution-specific components at inference, enabling zero-shot deployment on previously unseen sites. We evaluate DALMA on a multi-center benchmark comprising seven datasets from three countries. DALMA consistently achieves state-of-the-art zero-shot microbial identification across two held-out clinical centers, while the learned representations also transfer effectively to antimicrobial resistance prediction. Furthermore, latent-space novelty estimation enables reliable selective prediction under previously unseen domain shifts. These results demonstrate that biologically informed representation learning provides an effective strategy for robust and transferable ML in clinical microbiology.
Attention mechanisms have been widely utilized in modern deep learning, and many existing multi-omics models inherit their conventional use to allow unrestricted bidirectional interactions. However, the fundamental logic of life is directional. Existing designs often overlook the directionality suggested by the central dogma, potentially limiting transfer across heterogeneous cancers, downstream tasks, and incomplete modality settings.In this work, we present DoGMA, a central-dogma-guided foundation model for pan-cancer multi-omics analysis, arguing that robust transfer requires representations with domain-specific inductive bias. Concretely, we build it on a Transformer-MoE architecture where directed attention biases inter-omics communication toward central-dogma information flow. We further pretrain our model with masked hierarchical omics reconstruction to guide it toward learning central-dogma-consistent interactions. Across diverse downstream tasks, including cancer representation learning, survival prediction, and metastasis prediction, DoGMA consistently demonstrates strong predictive performance. Ablations and analyses further suggest that the performance gains arise from the synergy between central-dogma-guided directed attention and reconstruction-based pretraining, which together promote more biologically consistent cross-omics information exchange. Overall, DoGMA demonstrates that domain-specific inductive biases can improve the robustness and transferability of multi-omics foundation models, offering new insights into the design of attention mechanisms for multi-omics representation learning.
Maulik Chevli, Johannes Brandt, Rickmer Braren +2cs.CV cs.AI
Routine CT interpretation is inherently comprehensive, capturing incidental findings across the entire scan volume. 3D CT foundation models could assist this process by providing generalizable representations of anatomy and pathology. To evaluate their diagnostic breadth, we benchmark ten frozen CT encoders across three cohorts of thoracic CT scans, including an unseen internal clinical dataset, using $k$-nearest neighbors, zero-shot prompting, and linear probing. We find no universal state-of-the-art, with rankings fluctuating significantly depending on the evaluation context. While models combining fine-grained image tokenization with vision-language alignment generally perform best, a lightweight supervised encoder remains highly competitive, demonstrating that explicit labels can effectively substitute for scale. Crucially, rather than model architecture, we observe that the primary determinant of performance is a physical bottleneck: a finding's detectability scales with its contrast against surrounding tissue and its spatial extent. Through controlled within-organ comparisons, we empirically demonstrate that widespread or high-contrast abnormalities, such as devices and effusions, are reliably recovered. Conversely, small, low-contrast focal lesions remain a persistent challenge across all evaluated encoders. We attribute this to the inherent limitations of globally pooled embeddings, suggesting that accurately representing small, low-contrast structures will require region- or lesion-level pretraining.
Single-cell transcriptomes are sparse observations of coordinated biological programmes, yet most self-supervised models learn by reconstructing individual genes. Here we present BioM-JEPA, a joint-embedding predictive architecture that instead predicts aggregate representations of graph-connected gene blocks defined by protein-association and corpus-derived coexpression evidence. A student network infers each target-block representation from the remaining genes in a cell, while a slowly updated teacher supplies the corresponding target from the full observed gene set. Under the reported extraction procedure, block-level prediction produced embeddings with higher effective rank and weaker association with detected-gene depth in the tested diagnostics than token-prediction, random-block and reconstruction controls. Across CellBench tasks, frozen BioM-JEPA embeddings retained expression, pathway and neighbourhood information and achieved the lowest aggregate perturbation-response error among the evaluated models. Representation diagnostics were also consistent with canonical pancreatic programmes and compositional relationships between genetic perturbations. Linear attention avoids constructing a quadratic gene-by-gene attention matrix; in a matched one-epoch hPancreas experiment at batch size 8, BioM-JEPA provided 5.75-fold higher fine-tuning throughput and 3.76-fold higher held-out embedding throughput than scFoundation. Together, these results support graph-connected gene blocks as useful prediction units for JEPA-style representation learning in single-cell biology.
Dominika Kunc, Przemysław Kazienko, Stanisław Saganowskics.LG cs.AI
While Self-Supervised Learning (SSL) effectively extracts general representations from noisy, unconstrained physiological signals such as photoplethysmography (PPG), its suitability for highly subjective tasks remains unproven. In this work, we evaluate the efficacy of PPG-based SSL for real-life intense emotion detection. First, we pretrain a Real-Life PPG encoder (RL-PPG) on unconstrained, real-life data. As a rigorous sanity check, we demonstrate that these representations transfer exceptionally well to an objective physical activity recognition task, yielding almost 5-fold increase in performance over baselines in a leave-one-subject-out evaluation (LOSO). However, when applied to a~subjective real-life emotion detection task, these same general representations fail to surpass naive baselines under the LOSO protocol. Using an Across-Time validation strategy, we establish that incorporating an individual's personal data during fine-tuning is the main driver of predictive performance, outweighing the benefits of population-level pretraining. Ultimately, our findings indicate that in the evaluated scenario, general SSL representations may be insufficient for subjective affective inference, suggesting that personalization is likely a key component for real-world emotion recognition. To support future research, we share the code and pretrained RL-PPG~encoder~weights.
Increasing EEG pretraining data scale or model capacity does not consistently improve downstream performance. We identify a persistent low-frequency bias in representations learned by diverse EEG foundation models, which remains across dataset scales, model capacities, and pretraining objectives. Our analysis links this bias to the interaction between EEG's $1/f^α$-like spectral structure and neural networks' tendency to preferentially learn low-frequency components. In masked autoencoders, the $\ell_2$ reconstruction objective further amplifies this imbalance: under comparable relative reconstruction errors, high-power low-frequency components contribute disproportionately to the loss. To address this issue, we introduce FAME, a frequency-balanced masked autoencoding framework that reconstructs time--frequency activity in predefined EEG bands from masked EEG inputs. FAME independently standardizes the reconstruction targets within each band and assigns equal weight to all band-specific losses, thereby balancing supervision across the EEG spectrum. Evaluated on 41 downstream tasks in OmniEEG-Bench, FAME learns more spectrally balanced representations and achieves state-of-the-art performance on 24 of them. These results underscore the importance of balanced spectral supervision for learning transferable EEG representations.
Fine-grained visual representations are essential for medical image analysis, particularly when diagnostically relevant evidence is subtle and spatially localized. Modern transformer-based medical vision encoders must therefore learn patch-level representations that are both clinically meaningful and spatially consistent. Without these properties, large vision-language models (LVLMs) operate on an ambiguous visual foundation, limiting their ability to generate clinically reliable and spatially grounded responses. However, existing training strategies for medical vision encoders rarely achieve both objectives. Image-text alignment provides clinically meaningful supervision primarily at the image level, leaving the spatial localization of diagnostic evidence weakly constrained. In contrast, self-supervised learning promotes spatial consistency but lacks the semantic supervision needed to distinguish visually similar yet clinically distinct regions. To address this gap, we present LoFi, a medical vision foundation model built on location-aware fine-grained representation learning. LoFi trains a vision encoder with a lightweight large language model under grounding and grounded captioning objectives. Because these objectives require predicting location from clinical text and vice versa, spatial consistency emerges without any explicit patch-level regularization. To enable training at scale, we construct MedG, a large-scale medical grounding dataset of 4.48M image-text-box triplets curated from 84 datasets spanning 7 modalities. Across phrase grounding, visual question answering, and region-based organ classification under perturbations, LoFi consistently outperforms general-purpose and medical vision foundation models as well as state-of-the-art LVLMs. Code is available at https://github.com/myeongkyunkang/lofi-medg.
Photoplethysmography (PPG) is widely used in consumer wearables because of its low cost and ease of acquisition. However, unlike electrocardiography (ECG), PPG measures peripheral pulse dynamics rather than cardiac electrical activity, limiting its ability to predict cardiac conditions that rely on ECG-specific morphological cues. Existing methods attempt to bridge this gap by reconstructing ECG signals from PPG signals. However, this inverse mapping is inherently ill-posed, and faithful waveform reconstruction does not necessarily translate into improved downstream performance. To address this challenge, we propose P2E-VQ, a retrieval-augmented framework that replaces ECG waveform reconstruction with ECG-linked representation retrieval. Specifically, P2E-VQ converts PPG patches into discrete tokens and retrieves ECG-linked information from a memory bank constructed exclusively from the training data. This process augments PPG representations while requiring only PPG signals during inference. Extensive experiments on five public datasets covering six downstream tasks, including clinical endpoint prediction and affective state recognition, demonstrate that P2E-VQ consistently outperforms pretrained baselines under a unified frozen-feature linear-probing protocol.
Deep learning has shown strong potential in medical image analysis, but most existing methods rely on large-scale annotations and a closed-world assumption that rarely holds in clinical practice. Although Generalized Category Discovery (GCD) has advanced rapidly on natural images, it remains underexplored in medical imaging. To address this issue, we propose MedXplore, a unified framework for reliable and unbiased medical GCD, optimizing from both perceptual and decision levels. Specifically, at the perceptual level, taking a frequency domain perspective, Frequency-SNR Adaptive Attention and Consistency (FAAC) performs learnable full-spectrum filtering and global-local energy contrast activation to not only highlight local abnormal signals relative to the global context, but also provide reliable semantic anchors for patch consistency learning. At the decision level, Adaptive Cosine-Angular Margin (ACAM) adjusts angular margins using semantic difficulty and feature confidence to balance intra-class compactness and inter-class separability. Together, the two modules improve lesion-sensitive representation learning and mitigate old-class bias. Experiments on multiple benchmarks show an average \textbf{8.5\%} gain in \textit{All} accuracy over the strongest competing methods. On Kvasir, MedXplore reduces false-old errors from 14.50\% to 0.80\%, demonstrating strong robustness under severe old-new ambiguity.
EEG-based disease diagnosis requires one prediction per subject, yet common pipelines segment recordings into short instances, inherit the subject label for every instance, and train instance-level classifiers. This assumes that all instances provide equally reliable diagnostic evidence. Multiple instance learning (MIL) avoids inherited labels by treating each subject as a bag. However, EEG datasets contain far fewer subjects than instances, which can limit the quality of the representations learned by end-to-end MIL. We propose BridgeMIL, a two-stage framework that decouples instance representation learning from subject-level supervision. Stage 1 pretrains the encoder without inherited instance labels by aligning temporally nearby windows and independently sampled within-subject sub-bags. Variance and covariance regularization prevent collapse and reduce redundancy without negative pairs. Stage 2 transfers the encoder to an attention-based MIL aggregator, applies supervision only to subject predictions, and limits representation drift through feature retention. Across three EEG disease datasets and five representative backbones, BridgeMIL attains the highest mean accuracy in 14 of 15 dataset-backbone settings and an overall mean accuracy of 76.57%, 4.28 percentage points higher than the strongest baseline. Further analyses reveal substantial variation in inherited-label reliability across instances, greater performance sensitivity to subject scarcity than to instance scarcity, and a more structured representation space with distinct subject-wise clusters and improved separation between diagnostic classes. Together, these findings underscore the importance of aligning supervision with the subject-level prediction objective while learning from abundant EEG instances without assigning disease labels to individual instances.
Understanding disease trajectories from longitudinal clinical data remains challenging due to complex temporal dynamics and heterogeneous patient cohorts. Here, we present a contrastive representation learning framework that models multivariate disease trajectories as temporal graphs and learns representations using contrastive graph neural networks. Nodes represent patient observations over time, while edges capture temporal continuity and structural similarity between trajectories. Structure-aware random walks guide contrastive learning to generate embeddings that preserve temporal context and trajectory topology. The resulting representations enable robust clustering of patients with similar disease progression patterns and reveal latent structure in longitudinal data.
A CT examination captures multiple organs, but many biomedical questions concern abnormalities, prognosis, or longitudinal change in a specific organ. These questions require a separate representation for each organ within the same CT volume. Existing CT foundation models commonly produce a single volume-level representation, while recent anatomy-aware methods either encode pre-separated organ volumes or explicitly disentangle images into organ token groups. The former may remove clinically relevant surrounding context, while the latter does not condition a shared encoder on a selected organ before its features are formed. We introduce OrganLens for organ-specific representation learning through self-supervision. An organ identity conditions a shared CT encoder, while organ-specific distillation and anatomy-mask supervision shape features for anatomy-weighted pooling into organ-specific representations. At inference, the shared model produces 11 organ-specific representations without external segmentation masks. We evaluate OrganLens on CT-RATE, RAD-ChestCT, INSPECT, and NLST across diverse acquisitions and downstream evaluations. Relative to CT-pretrained DINOv2, heart representations raise CT-RATE cardiomegaly AUROC from 0.910 to 0.953, while lung representations improve the Harrell C-index for NLST lung-cancer mortality by 14.2\%. The global representation reaches INSPECT Recall@10 of 33.09\% and 32.04\% for text-to-image and image-to-text retrieval, respectively. Across organ-related tasks, anatomically matched representations provide stronger task-relevant signal, while the global representation retains broad utility. OrganLens offers a scalable approach to organ-specific CT representation learning with a shared encoder. More broadly, it provides the medical research community with a reusable framework for studying organ-specific disease across cohorts and clinical endpoints.
Medical image encoders from different groups are increasingly treated as interchangeable, on the assumption that scale and clinical supervision concentrate their representations onto a shared structure. Whether this convergence is real, what produces it, and whether it is clinically usable are untested, and the similarity measures behind such claims are fragile. We present a controlled dissection across 18 image and 7 text encoders, all open-weight and run locally, spanning 7M to 27B parameters and five imaging modalities, including 650,982 chest radiographs from six datasets. To isolate cause, we train encoders that vary only the objective under fixed data, architecture, and scale, and reproduce the effect in a synthetic model. Convergence is modest but above a random floor, driven by the self-supervised objective, not clinical supervision: matched self-supervised encoders aligned most (40.4% on chest radiography), with label-supervised (21.1%) and image-text (3.3%) far lower, and did not grow with size (Spearman 0.302, p=0.223) or capability. It is within-modality, does not reach clinical language, and does not reproduce how radiologists judge case similarity. Yet a linear classifier transfers across encoders and to five held-out hospitals, retaining about 85% of within-encoder performance. Convergence in medical imaging is therefore set by the pretraining objective, not inherited from scale or clinical supervision. Interoperability is accordingly something to design for through that objective, and to validate where the shared geometry is weakest, across patient subgroups and against clinical judgment.
Rajat Vashistha, Sandra Brosda, Lauren G. Aoude +8cs.CV
We propose a weakly supervised 18FFDG PET representation-learning framework for content based medical image retrieval, using H&E derived information during training while preserving PET-only inference. The proposed method was designed to use H&E derived information during training while maintaining PET only inference. A teacher student training strategy was used to learn the PET tumour derived voxel representations, from which global and hotspot conditioned embeddings were generated along with maps of intra tumour heterogeneity in our oesophegeal cancer test case. A progressive ablation strategy was used to evaluate the contribution of different supervision mechanisms. Retrieval performance was assessed across cross-validation folds using metrics including mean average precision, normalised discounted cumulative gain and mean reciprocal rank. Additional analyses evaluated ablation performance, hotspot faithfulness through perturbation/deletion experiments, prototype-specific PET uptake behaviour and indirect patient level concordance between learned PET prototype classes and selected histomic features. Progressive introduction of pathology informed supervision and hotspot modelling improved PET retrieval performance compared with global PET representations and conventional PET baselines. Across the ablation ladder, PET hotspot conditioned representations consistently provided stronger retrieval than global embeddings, indicating that focusing on informative tumour subregions improved sensitivity to intra tumour heterogeneity. Histopathology concordance further showed that the learned classes were not simply high uptake PET regions; instead, they demonstrated distinct heterogeneity in 18F FDG uptake.
Single-cell light microscopy images have become an important data source for characterizing cell phenotypes, but their complexity and heterogeneity pose challenges to high-throughput automated analysis. Existing representation learning methods mostly rely on task-oriented modeling, which is limited by specific datasets and predefined tasks, making them difficult to generalize across different cell types and microscopy modalities, and experimental conditions. Although general-purpose methods have improved the generalization ability of image representation in recent years, their limited utilization of experimental background and biological context information still poses challenges in complex phenotypic analysis. Here, we propose scMIR, a vision-language foundation model for single-cell light microscopy image representation. By synergistically combining self-supervised image reconstruction with text-guided cross-modal alignment, scMIR can simultaneously encode morphological and biological semantic information in a unified representation space. scMIR is pre-trained on 207,957 image-text pairs, covering various cell types, microscopy modalities, and perturbation conditions. scMIR outperforms existing general models and task-oriented methods as systematically evaluated on various complex tasks using 16 benchmark datasets, including cell classification, clustering, phenotype inference, and batch effect correction tasks. Furthermore, scMIR shows a strong generalization ability across various tasks without requiring task-specific fine-tuning. With its unique advantages, we envision scMIR may promote the standardization and automation of high-throughput phenotyping workflows through supporting various downstream analysis tasks.
Early sepsis prediction from electronic health records is challenged by irregular sampling, high missingness, and class imbalance. We systematically compare four modeling paradigms -- self-supervised Joint Embedding Predictive Architecture (JEPA) via masked latent prediction, self-supervised VICReg (variance-invariance-covariance regularization) with two-view augmentation, semi-supervised fine-tuning of a VICReg-pretrained encoder, and supervised Temporal Convolutional Network (TCN) -- alongside raw-feature baselines. All models share a common preprocessing pipeline of hourly binning with forward-fill imputation applied to 7 biomarkers selected via sparsity analysis from the MIMIC-III dataset. Our best model (JEPA + XGBoost + mean pooling) achieves AUPRC 0.636 at the time of onset (H0), approaching the SupMix benchmark (0.667) while using 83\% fewer biomarkers. The Tier 1 pipeline -- VICReg pretraining followed by semi-supervised fine-tuning and XGBoost -- achieves AUPRC 0.510 at H0, a 3.1$\times$ improvement over the raw-feature baseline (0.165) and a 7.6\% improvement over the end-to-end supervised TCN (0.474). Crucially, the fine-tuned VICReg encoder exhibits the most temporally persistent representations, degrading only 16.8\% from H0 to H10 compared to 47.5\% for supervised TCN and 65.3\% for JEPA, demonstrating that self-supervised pretraining with task-aware fine-tuning yields features that are both sharp near onset and robust across prediction horizons.