CheXmix: Unified Generative Pretraining for Vision Language Models in Medical Imaging

Recent medical multimodal foundation models are built as multimodal LLMs (MLLMs) by connecting a CLIP-pretrained vision encoder to an LLM using LLaVA-style finetuning. This two-stage, decoupled approach introduces a projection layer that can distort visual features. This is especially concerning in medical imaging where subtle cues are essential for accurate diagnoses. In contrast, early-fusion generative approaches such as Chameleon eliminate the projection bottleneck by processing image and text tokens within a single unified sequence, enabling joint representation learning that leverages the inductive priors of language models. We present CheXmix, a unified early-fusion generative model trained on a large corpus of chest X-rays paired with radiology reports. We expand on Chameleon's autoregressive framework by introducing a two-stage multimodal generative pretraining strategy that combines the representational strengths of masked autoencoders with MLLMs. The resulting models are highly flexible, supporting both discriminative and generative tasks at both coarse and fine-grained scales. Our approach outperforms well-established generative models across all masking ratios by 6.0% and surpasses CheXagent by 8.6% on AUROC at high image masking ratios on the CheXpert classification task. We further inpaint images over 51.0% better than text-only generative models and outperform CheXagent by 45% on the GREEN metric for radiology report generation. These results demonstrate that CheXmix captures fine-grained information across a broad spectrum of chest X-ray tasks. Our code is at: https://github.com/StanfordMIMI/CheXmix.

A Reasoning-Enabled Vision-Language Foundation Model for Chest X-ray Interpretation

Chest X-rays (CXRs) are among the most frequently performed imaging examinations worldwide, yet rising imaging volumes increase radiologist workload and the risk of diagnostic errors. Although artificial intelligence (AI) systems have shown promise for CXR interpretation, most generate only final predictions, without making explicit how visual evidence is translated into radiographic findings and diagnostic predictions. We present CheXOne, a reasoning-enabled vision-language model for CXR interpretation. CheXOne jointly generates diagnostic predictions and explicit, clinically grounded reasoning traces that connect visual evidence, radiographic findings, and these predictions. The model is trained on 14.7 million instruction and reasoning samples curated from 30 public datasets spanning 36 CXR interpretation tasks, using a two-stage framework that combines instruction tuning with reinforcement learning to improve reasoning quality. We evaluate CheXOne in zero-shot settings across visual question answering, report generation, visual grounding and reasoning assessment, covering 17 evaluation settings. CheXOne outperforms existing medical and general-domain foundation models and achieves strong performance on independent public benchmarks. A clinical reader study demonstrates that CheXOne-drafted reports are comparable to or better than resident-written reports in 55% of cases, while effectively addressing clinical indications and enhancing both report writing and CXR interpretation efficiency. Further analyses involving radiologists reveal that the generated reasoning traces show high clinical factuality and provide causal support for the final predictions, offering a plausible explanation for the performance gains. These results suggest that explicit reasoning can improve model performance, interpretability and clinical utility in AI-assisted CXR interpretation.

Activation Matters: Test-time Activated Negative Labels for OOD Detection with Vision-Language Models

Out-of-distribution (OOD) detection aims to identify samples that deviate from in-distribution (ID). One popular pipeline addresses this by introducing negative labels distant from ID classes and detecting OOD based on their distance to these labels. However, such labels may present poor activation on OOD samples, failing to capture the OOD characteristics. To address this, we propose \underline{T}est-time \underline{A}ctivated \underline{N}egative \underline{L}abels (TANL) by dynamically evaluating activation levels across the corpus dataset and mining candidate labels with high activation responses during the testing process. Specifically, TANL identifies high-confidence test images online and accumulates their assignment probabilities over the corpus to construct a label activation metric. Such a metric leverages historical test samples to adaptively align with the test distribution, enabling the selection of distribution-adaptive activated negative labels. By further exploring the activation information within the current testing batch, we introduce a more fine-grained, batch-adaptive variant. To fully utilize label activation knowledge, we propose an activation-aware score function that emphasizes negative labels with stronger activations, boosting performance and enhancing its robustness to the label number. Our TANL is training-free, test-efficient, and grounded in theoretical justification. Experiments on diverse backbones and wide task settings validate its effectiveness. Notably, on the large-scale ImageNet benchmark, TANL significantly reduces the FPR95 from 17.5\% to 9.8\%. Codes are available at \href{https://github.com/YBZh/OpenOOD-VLM}{YBZh/OpenOOD-VLM}.

Learning Generalizable 3D Medical Image Representations from Mask-Guided Self-Supervision

Foundation models have transformed vision and language by learning general-purpose representations from large-scale unlabeled data, yet 3D medical imaging lacks analogous approaches. Existing self-supervised methods rely on low-level reconstruction or contrastive objectives that fail to capture the anatomical semantics critical for medical image analysis, limiting transfer to downstream tasks. We present MASS (MAsk-guided Self-Supervised learning), which treats in-context segmentation as the pretext task for learning general-purpose medical imaging representations. MASS's key insight is that automatically generated class-agnostic masks provide sufficient structural supervision for learning semantically rich representations. By training on thousands of diverse mask proposals spanning anatomical structures and pathological findings, MASS learns what semantically defines medical structures: the holistic combination of appearance, shape, spatial context, and anatomical relationships. We demonstrate effectiveness across data regimes: from small-scale pretraining on individual datasets (20-200 scans) to large-scale multi-modal pretraining on 5K CT, MRI, and PET volumes, all without annotations. MASS demonstrates: (i) few-shot segmentation on novel structures, (ii) matching full supervision with only 20-40\% labeled data while outperforming self-supervised baselines by over 20 in Dice score in low-data regimes, and (iii) frozen-encoder classification on unseen pathologies that matches full supervised training with thousands of samples. Mask-guided self-supervised pretraining captures broadly generalizable knowledge, opening a path toward 3D medical imaging foundation models without expert annotations. Code is available: https://github.com/Stanford-AIMI/MASS.

A data- and compute-efficient chest X-ray foundation model beyond aggressive scaling

Foundation models for medical imaging are typically pretrained on increasingly large datasets, following a "scale-at-all-costs" paradigm. However, this strategy faces two critical challenges: large-scale medical datasets often contain substantial redundancy and severe class imbalance that bias representation learning toward over-represented patterns, and indiscriminate training regardless of heterogeneity in data quality incurs considerable computational inefficiency. Here we demonstrate that active, principled data curation during pretraining can serve as a viable, cost-effective alternative to brute-force dataset enlargement. We introduce CheXficient, a chest X-ray (CXR) foundation model that selectively prioritizes informative training samples. CheXficient is pretrained on only 22.7% of 1,235,004 paired CXR images and reports while consuming under 27.3% of the total compute budget, yet achieving comparable or superior performance to its full-data counterpart and other large-scale pretrained models. We assess CheXficient across 20 individual benchmarks spanning 5 task types, including non-adapted off-the-shelf evaluations (zero-shot findings classification and crossmodal retrieval) and adapted downstream tasks (disease prediction, semantic segmentation, and radiology report generation). Further analyses show that CheXficient systematically prioritizes under-represented training samples, improving generalizability on long-tailed or rare conditions. Overall, our work offers practical insights into the data and computation demands for efficient pretraining and downstream adaptation of medical vision-language foundation models.

Unpaired Image-to-Image Translation via a Self-Supervised Semantic Bridge

Adversarial diffusion and diffusion-inversion methods have advanced unpaired image-to-image translation, but each faces key limitations. Adversarial approaches require target-domain adversarial loss during training, which can limit generalization to unseen data, while diffusion-inversion methods often produce low-fidelity translations due to imperfect inversion into noise-latent representations. In this work, we propose the Self-Supervised Semantic Bridge (SSB), a versatile framework that integrates external semantic priors into diffusion bridge models to enable spatially faithful translation without cross-domain supervision. Our key idea is to leverage self-supervised visual encoders to learn representations that are invariant to appearance changes but capture geometric structure, forming a shared latent space that conditions the diffusion bridges. Extensive experiments show that SSB outperforms strong prior methods for challenging medical image synthesis in both in-domain and out-of-domain settings, and extends easily to high-quality text-guided editing.

LUCID-SAE: Learning Unified Vision-Language Sparse Codes for Interpretable Concept Discovery

Sparse autoencoders (SAEs) offer a natural path toward comparable explanations across different representation spaces. However, current SAEs are trained per modality, producing dictionaries whose features are not directly understandable and whose explanations do not transfer across domains. In this study, we introduce LUCID (Learning Unified vision-language sparse Codes for Interpretable concept Discovery), a unified vision-language sparse autoencoder that learns a shared latent dictionary for image patch and text token representations, while reserving private capacity for modality-specific details. We achieve feature alignment by coupling the shared codes with a learned optimal transport matching objective without the need of labeling. LUCID yields interpretable shared features that support patch-level grounding, establish cross-modal neuron correspondence, and enhance robustness against the concept clustering problem in similarity-based evaluation. Leveraging the alignment properties, we develop an automated dictionary interpretation pipeline based on term clustering without manual observations. Our analysis reveals that LUCID's shared features capture diverse semantic categories beyond objects, including actions, attributes, and abstract concepts, demonstrating a comprehensive approach to interpretable multimodal representations.

Atlas is Your Perfect Context: One-Shot Customization for Generalizable Foundational Medical Image Segmentation

Accurate medical image segmentation is essential for clinical diagnosis and treatment planning. While recent interactive foundation models (e.g., nnInteractive) enhance generalization through large-scale multimodal pretraining, they still depend on precise prompts and often perform below expectations in contexts that are underrepresented in their training data. We present AtlasSegFM, an atlas-guided framework that customizes available foundation models to clinical contexts with a single annotated example. The core innovations are: 1) a pipeline that provides context-aware prompts for foundation models via registration between a context atlas and query images, and 2) a test-time adapter to fuse predictions from both atlas registration and the foundation model. Extensive experiments across public and in-house datasets spanning multiple modalities and organs demonstrate that AtlasSegFM consistently improves segmentation, particularly for small, delicate structures. AtlasSegFM provides a lightweight, deployable solution one-shot customization of foundation models in real-world clinical workflows. The code will be made publicly available.

Anatomy-VLM: A Fine-grained Vision-Language Model for Medical Interpretation

Accurate disease interpretation from radiology remains challenging due to imaging heterogeneity. Achieving expert-level diagnostic decisions requires integration of subtle image features with clinical knowledge. Yet major vision-language models (VLMs) treat images as holistic entities and overlook fine-grained image details that are vital for disease diagnosis. Clinicians analyze images by utilizing their prior medical knowledge and identify anatomical structures as important region of interests (ROIs). Inspired from this human-centric workflow, we introduce Anatomy-VLM, a fine-grained, vision-language model that incorporates multi-scale information. First, we design a model encoder to localize key anatomical features from entire medical images. Second, these regions are enriched with structured knowledge for contextually-aware interpretation. Finally, the model encoder aligns multi-scale medical information to generate clinically-interpretable disease prediction. Anatomy-VLM achieves outstanding performance on both in- and out-of-distribution datasets. We also validate the performance of Anatomy-VLM on downstream image segmentation tasks, suggesting that its fine-grained alignment captures anatomical and pathology-related knowledge. Furthermore, the Anatomy-VLM's encoder facilitates zero-shot anatomy-wise interpretation, providing its strong expert-level clinical interpretation capabilities.

Show and Segment: Universal Medical Image Segmentation via In-Context Learning

Medical image segmentation remains challenging due to the vast diversity of anatomical structures, imaging modalities, and segmentation tasks. While deep learning has made significant advances, current approaches struggle to generalize as they require task-specific training or fine-tuning on unseen classes. We present Iris, a novel In-context Reference Image guided Segmentation framework that enables flexible adaptation to novel tasks through the use of reference examples without fine-tuning. At its core, Iris features a lightweight context task encoding module that distills task-specific information from reference context image-label pairs. This rich context embedding information is used to guide the segmentation of target objects. By decoupling task encoding from inference, Iris supports diverse strategies from one-shot inference and context example ensemble to object-level context example retrieval and in-context tuning. Through comprehensive evaluation across twelve datasets, we demonstrate that Iris performs strongly compared to task-specific models on in-distribution tasks. On seven held-out datasets, Iris shows superior generalization to out-of-distribution data and unseen classes. Further, Iris's task encoding module can automatically discover anatomical relationships across datasets and modalities, offering insights into medical objects without explicit anatomical supervision.