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.

We study whether deep networks for medical imaging learn useful nonrobust features - predictive input patterns that are not human interpretable and highly susceptible to small adversarial perturbations - and how these features impact test performance. We show that models trained only on nonrobust features achieve well above chance accuracy across five MedMNIST classification tasks, confirming their predictive value in-distribution. Conversely, adversarially trained models that primarily rely on robust features sacrifice in-distribution accuracy but yield markedly better performance under controlled distribution shifts (MedMNIST-C). Overall, nonrobust features boost standard accuracy yet degrade out-of-distribution performance, revealing a practical robustness-accuracy trade-off in medical imaging classification tasks that should be tailored to the requirements of the deployment setting.

Vision Transformers $(\texttt{ViT})$ have become the architecture of choice for many computer vision tasks, yet their performance in computer-aided diagnostics remains limited. Focusing on breast cancer detection from mammograms, we identify two main causes for this shortfall. First, medical images are high-resolution with small abnormalities, leading to an excessive number of tokens and making it difficult for the softmax-based attention to localize and attend to relevant regions. Second, medical image classification is inherently fine-grained, with low inter-class and high intra-class variability, where standard cross-entropy training is insufficient. To overcome these challenges, we propose a framework with three key components: (1) Region of interest $(\texttt{RoI})$ based token reduction using an object detection model to guide attention; (2) contrastive learning between selected $\texttt{RoI}$ to enhance fine-grained discrimination through hard-negative based training; and (3) a $\texttt{DINOv2}$ pretrained $\texttt{ViT}$ that captures localization-aware, fine-grained features instead of global $\texttt{CLIP}$ representations. Experiments on public mammography datasets demonstrate that our method achieves superior performance over existing baselines, establishing its effectiveness and potential clinical utility for large-scale breast cancer screening. Our code is available for reproducibility here: https://aih-iitd.github.io/publications/attend-what-matters

Accurate prognostication and risk estimation are essential for guiding clinical decision-making and optimizing patient management. While radiologist-assessed features from CT scans provide valuable indicators of disease severity and outcomes, interpreting such images requires expert knowledge, and translating rich visual information into textual summaries inevitably leads to information loss. In this work, we propose a vision-language framework for 3D CT image understanding that leverages large-scale open-sourced CT images paired with radiology reports through visual instruction tuning. This pre-training enables the model to learn clinically meaningful visual-textual representations, which can then be adapted to downstream survival prediction tasks. By incorporating a survival prediction head on top of the pre-trained model, our approach improves survival prediction from CT images and clinical data while generating clinically meaningful language responses to predefined questions. Experimental results demonstrate that our method outperforms baseline methods in survival prediction, particularly, when clinical data alone is less predictive. The code will be released upon acceptance.

The integration of medical imaging and clinical text has enabled the emergence of generalist artificial intelligence (AI) systems for healthcare. However, pervasive biases, such as imbalanced disease prevalence, skewed anatomical region distributions, heterogeneous imaging protocols, and demographic disparities, pose significant challenges to the fairness and reliability of vision-language systems in real-world clinical settings. Here we present BiasCareVL, a bias-aware multimodal learning framework that introduces bias control directly into model design, rather than treating it as a post hoc correction. BiasCareVL incorporates adaptive uncertainty modeling with optional human-in-the-loop refinement to regulate the influence of dominant data patterns and to promote equitable reasoning under distributional imbalance. Trained on 3.44 million samples spanning over 15 imaging modalities, the framework supports diverse clinical tasks, including visual question answering, disease classification, segmentation, and report generation within a unified representation space. Across eight public benchmarks covering dermatology, oncology, radiology, and pathology, BiasCareVL consistently outperforms 20 state-of-the-art methods, with pronounced gains in clinically challenging scenarios, including over 10% accuracy improvement in multi-class skin lesion diagnosis and more than 20% Dice improvement in small tumor segmentation. Furthermore, BiasCareVL achieves diagnostic performance exceeding human accuracy with substantially reduced time requirements when evaluated with board-certified radiologists. By open-sourcing BiasCareVL, we aim to promote a transparent, reproducible, and equitable future for AI in healthcare, paving the way for general-purpose, trustworthy, and clinically reliable AI systems.

Masked image modeling (MIM) is a highly effective self-supervised learning (SSL) approach to extract useful feature representations from unannotated data. Predominantly used random masking methods make SSL less effective for medical images due to the contextual similarity of neighboring patches, leading to information leakage and SSL simplification. Hierarchical shifted window (Swin) transformer, a highly effective approach for medical images cannot use advanced masking methods as it lacks a global [CLS] token. Hence, we introduced an attention guided masking mechanism for Swin within a co-distillation learning framework to selectively mask semantically co-occurring and discriminative patches, to reduce information leakage and increase the difficulty of SSL pretraining. However, attention guided masking inevitably reduces the diversity of attention heads, which negatively impacts downstream task performance. To address this, we for the first time, integrate a noisy teacher into the co-distillation framework (termed DAGMaN) that performs attentive masking while preserving high attention head diversity. We demonstrate the capability of DAGMaN on multiple tasks including full- and few-shot lung nodule classification, immunotherapy outcome prediction, tumor segmentation, and unsupervised organs clustering.

Medical image segmentation (MIS) is a fundamental component of computer-assisted diagnosis and clinical decision support. Over the past decade, numerous architectures specifically tailored to medical imaging have emerged to address domain-specific challenges such as low contrast, small anatomical structures, and limited annotated data. In parallel, rapid progress in computer vision has produced highly capable general-purpose vision models (GP-VMs) originally designed for natural images. Despite their strong performance on standard vision benchmarks, their effectiveness for MIS remains insufficiently understood. In this controlled empirical study, we examine whether specialized medical segmentation architectures (SMAs) provide systematic advantages over modern GP-VMs for 2D MIS. We compare eleven SMAs and GP-VMs using a unified training and evaluation protocol across three heterogeneous datasets, each covering different 2D imaging modalities, class structures, and data characteristics. Beyond segmentation performance, we employ linear mixed-effects models (LMMs) for statistical assessment and qualitative Grad-CAM visualizations to investigate explainability (XAI)-related model behavior. Our results imply that, for the analyzed settings, GP-VMs achieve performance comparable to that of specialized MIS models. Moreover, XAI analyses indicate that GP-VMs are capable of identifying clinically relevant structures despite the absence of explicit domain-specific architectural priors. These findings suggest that GP-VMs can represent a viable alternative to domain-specific methods for 2D MIS, highlighting the importance of informed model selection. All code and resources are available at GitHub.

Differential privacy (DP)'s effect in medical imaging is typically evaluated only through end-to-end performance, leaving the mechanism of privacy-induced utility loss unclear. We introduce Differential Privacy Representation Geometry for Medical Imaging (DP-RGMI), a framework that interprets DP as a structured transformation of representation space and decomposes performance degradation into encoder geometry and task-head utilization. Geometry is quantified by representation displacement from initialization and spectral effective dimension, while utilization is measured as the gap between linear-probe and end-to-end utility. Across over 594,000 images from four chest X-ray datasets and multiple pretrained initializations, we show that DP is consistently associated with a utilization gap even when linear separability is largely preserved. At the same time, displacement and spectral dimension exhibit non-monotonic, initialization- and dataset-dependent reshaping, indicating that DP alters representation anisotropy rather than uniformly collapsing features. Correlation analysis reveals that the association between end-to-end performance and utilization is robust across datasets but can vary by initialization, while geometric quantities capture additional prior- and dataset-conditioned variation. These findings position DP-RGMI as a reproducible framework for diagnosing privacy-induced failure modes and informing privacy model selection.

In critical decision support systems based on medical imaging, the reliability of AI-assisted decision-making is as relevant as predictive accuracy. Although deep learning models have demonstrated significant accuracy, they frequently suffer from miscalibration, manifested as overconfidence in erroneous predictions. To facilitate clinical acceptance, it is imperative that models quantify uncertainty in a manner that correlates with prediction correctness, allowing clinicians to identify unreliable outputs for further review. To address this necessity, this paper proposes a probabilistic optimization framework grounded in Bayesian deep learning. Specifically, the Confidence-Uncertainty Boundary Curve (CUBC) is first explored as an intermediate operational target. Grounded in this target, a novel Confidence-Uncertainty Boundary Loss (CUB-Loss) is proposed to regularize the alignment between prediction confidence and uncertainty estimates during training, imposing penalties on high-certainty errors and low-certainty correct predictions. Upon completion of training optimization, a Boundary Curve Calibration Error (BCCE) metric is further introduced to measure the degree of boundary alignment in the calibrated model. Building on this measurement, a Dual Temperature Scaling (DTS) strategy is devised to perform post-hoc refinement, further adjusting the posterior predictive distribution across different confidence-uncertainty regions. The proposed framework is validated on three distinct medical imaging tasks: automatic screening of pneumonia, diabetic retinopathy detection, and identification of skin lesions. Empirical results demonstrate that the proposed approach improves uncertainty calibration across diverse modalities, maintains robust performance in data-scarce scenarios, and remains effective on severely imbalanced datasets, underscoring its potential for real clinical deployment.

Deep learning has substantially advanced medical image segmentation, yet achieving robust generalization across diverse imaging modalities and anatomical structures remains a major challenge. A key contributor to this limitation lies in how existing architectures, ranging from CNNs to Transformers and their hybrids, primarily encode spatial information while overlooking frequency-domain representations that capture rich structural and textural cues. Although recent studies have begun exploring spectral information at the feature level, supervision-level integration of frequency cues-crucial for fine-grained object localization-remains largely untapped. To this end, we propose Phi-SegNet, a CNN-based architecture that incorporates phase-aware information at both architectural and optimization levels. The network integrates Bi-Feature Mask Former (BFMF) modules that blend neighboring encoder features to reduce semantic gaps, and Reverse Fourier Attention (RFA) blocks that refine decoder outputs using phase-regularized features. A dedicated phase-aware loss aligns these features with structural priors, forming a closed feedback loop that emphasizes boundary precision. Evaluated on five public datasets spanning X-ray, US, histopathology, MRI, and colonoscopy, Phi-SegNet consistently achieved state-of-the-art performance, with an average relative improvement of 1.54+/-1.26% in IoU and 0.98+/-0.71% in F1-score over the next best-performing model. In cross-dataset generalization scenarios involving unseen datasets from the known domain, it also exhibits robust and superior performance, highlighting its adaptability and modality-agnostic design. These findings demonstrate the potential of leveraging spectral priors in both feature representation and supervision, paving the way for generalized segmentation frameworks that excel in fine-grained object localization. Our code is available on GitHub.

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. Such opaque reasoning processes lack reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

Recent tool-use frameworks powered by vision-language models (VLMs) improve image understanding by grounding model predictions with specialized tools. Broadly, these frameworks leverage VLMs and a pre-specified toolbox to decompose the prediction task into multiple tool calls (often deep learning models) which are composed to make a prediction. The dominant approach to composing tools is using text, via function calls embedded in VLM-generated code or natural language. However, these methods often perform poorly on medical image understanding, where salient information is encoded as spatially-localized features that are difficult to compose or fuse via text alone. To address this, we propose a tool-use framework for medical image understanding called the Tool Bottleneck Framework (TBF), which composes VLM-selected tools using a learned Tool Bottleneck Model (TBM). For a given image and task, TBF leverages an off-the-shelf medical VLM to select tools from a toolbox that each extract clinically-relevant features. Instead of text-based composition, these tools are composed by the TBM, which computes and fuses the tool outputs using a neural network before outputting the final prediction. We propose a simple and effective strategy for TBMs to make predictions with any arbitrary VLM tool selection. Overall, our framework not only improves tool-use in medical imaging contexts, but also yields more interpretable, clinically-grounded predictors. We evaluate TBF on tasks in histopathology and dermatology and find that these advantages enable our framework to perform on par with or better than deep learning-based classifiers, VLMs, and state-of-the-art tool-use frameworks, with particular gains in data-limited regimes. The project details and the code are available at https://christinaliu2020.github.io/tbm/.

Medical image segmentation is fundamental for biomedical discovery. Existing methods lack generalizability and demand extensive, time-consuming manual annotation for new clinical application. Here, we propose MedSAM-3, a text promptable medical segmentation model for medical image and video segmentation. By fine-tuning the Segment Anything Model (SAM) 3 architecture on medical images paired with semantic conceptual labels, our MedSAM-3 enables medical Promptable Concept Segmentation (PCS), allowing precise targeting of anatomical structures via open-vocabulary text descriptions rather than solely geometric prompts. We further introduce the MedSAM-3 Agent, a framework that integrates Multimodal Large Language Models (MLLMs) to perform complex reasoning and iterative refinement in an agent-in-the-loop workflow. Comprehensive experiments across diverse medical imaging modalities, including X-ray, MRI, Ultrasound, CT, and video, demonstrate that our approach significantly outperforms existing specialist and foundation models. We will release our code and model at https://github.com/Joey-S-Liu/MedSAM3.

Despite notable progress in text-guided medical image segmentation nowadays, these methods are limited to single-round dialogues and fail to support multi-round reasoning, which is important for medical education scenarios. In this work, we introduce Multi-Round Entity-Level Medical Reasoning Segmentation (MEMR-Seg), a new task that requires generating segmentation masks through multi-round queries with entity-level reasoning, helping learners progressively develop their understanding of medical knowledge. To support this task, we construct MR-MedSeg, a large-scale dataset of 177K multi-round medical segmentation dialogues, featuring entity-based reasoning across rounds. Furthermore, we propose MediRound, an effective baseline model designed for multi-round medical reasoning segmentation. To mitigate the inherent error propagation within the chain-like pipeline of multi-round segmentation, we introduce a lightweight yet effective Judgment & Correction Mechanism during model inference. Experimental results demonstrate that our method effectively addresses the MEMR-Seg task and outperforms conventional medical referring segmentation methods. The project is available at https://github.com/Edisonhimself/MediRound.

Computer-aided medical image analysis is crucial for disease diagnosis and treatment planning. While vision-language models (VLMs) such as CLIP exhibit strong generalization ability, their direct application to medical imaging remains hindered by a substantial domain gap. Existing methods for bridging this gap, including prompt learning and unidirectional modality interaction, typically introduce domain knowledge into only one modality. However, such approaches fail to fully exploit CLIP's inherent dual-modality structure and overlook the synergistic effect of bidirectional cross-modal interaction, resulting in persistent modality misalignment. In this paper, we propose NEARL (iNteracted quEry Adaptation with oRthogonaL Regularization), a novel parameter-efficient VLM framework for bidirectional cross-modal interaction. NEARL consists of two key components: (1) the Unified Synergy Embedding Transformer (USEformer), which dynamically generates compact cross-modal queries to facilitate interaction; and (2) the Orthogonal Cross-Attention Adapter (OCA), which decouples new knowledge into truly novel and incremental components through orthogonal regularization. This design reduces interference from incremental components, enabling more focused learning of novel information and improving modality interaction in VLMs. Notably, NEARL introduces only 1.46M learnable parameters. Extensive experiments on three medical imaging modalities demonstrate state-of-the-art performance (e.g., a 2.3% relative improvement on the pneumonia dataset), along with fast inference and low memory overhead, highlighting its effectiveness for real-world medical vision-language understanding.

Current methods for multimodal medical image classification (M3IC) face two major challenges. First, the prevailing "fusion after unimodal image embedding" paradigm cannot fully exploit the complementary and correlated information in the multimodal data. Second, the scarcity of labeled multimodal medical images, coupled with their substantial domain shift from natural images, impedes the use of cutting-edge Vision Foundation Models (VFMs) for medical image embedding. To jointly address the challenges, we propose a novel Early Intervention (EI) framework. Treating one modality as target and the rest as reference, EI harnesses high-level semantic tokens from the reference as intervention tokens to steer the target modality's embedding process at an early stage. For parameter-efficient VFM adaptation, we introduce Mixture of varied-rank LoRAs (MoR), which employs a small set of LoRA experts with distinct ranks and a bypass-allowed router. Extensive experiments on three public datasets, covering retinal disease recognition, skin lesion recognition, and knee anomaly classification, verify the effectiveness of the proposed method against a number of competitive baselines.

As vision-language models (VLMs) are increasingly applied to medical AI, existing benchmarks mainly focus on evaluating their diagnostic ability over given medical images and texts, implicitly assuming that standardized medical images, texts, or question-answer pairs are already prepared. However, this assumption does not hold when we apply VLMs in real clinical practice, where medical data is often raw, heterogeneous, and fragmented across different sources. In this paper, we study this missing step, i.e., raw medical data standardization. Specifically, models are given raw dataset folders and evaluated on their ability to identify source formats, convert raw medical images into VLM-compatible visual inputs, extract relevant textual information, and organize the results into structured image-text pairs. To construct this Medical Data Standardization Benchmark (MDS-Bench), we manually annotate 1,939 raw medical data standardization tasks covering diverse clinical practice, radiology modalities, annotation formats, and directory layouts. Extensive experiments show that even the best performing VLM, i.e., Gemini 3 Flash, achieves only a 48.6% end-to-end success rate. Our research highlights raw medical data standardization as a critical bottleneck for medical AI diagnosis in real practice.