M. Varma
Publications
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}.
RadDiff: Describing Differences in Radiology Image Sets with Natural Language
Understanding how two radiology image sets differ is critical for generating clinical insights and for interpreting medical AI systems. We introduce RadDiff, a multimodal agentic system that performs radiologist-style comparative reasoning to describe clinically meaningful differences between paired radiology studies. RadDiff builds on a proposer-ranker framework from VisDiff, and incorporates four innovations inspired by real diagnostic workflows: (1) medical knowledge injection through domain-adapted vision-language models; (2) multimodal reasoning that integrates images with their clinical reports; (3) iterative hypothesis refinement across multiple reasoning rounds; and (4) targeted visual search that localizes and zooms in on salient regions to capture subtle findings. To evaluate RadDiff, we construct RadDiffBench, a challenging benchmark comprising 57 expert-validated radiology study pairs with ground-truth difference descriptions. On RadDiffBench, RadDiff achieves 47% accuracy, and 50% accuracy when guided by ground-truth reports, significantly outperforming the general-domain VisDiff baseline. We further demonstrate RadDiff's versatility across diverse clinical tasks, including COVID-19 phenotype comparison, racial subgroup analysis, and discovery of survival-related imaging features. Together, RadDiff and RadDiffBench provide the first method-and-benchmark foundation for systematically uncovering meaningful differences in radiological data.