Mu Wei

Sheng Zhang, Yanbo Xu, Naoto Usuyama et al. · cambridge, microsoft-research

Biomedical data is inherently multimodal, comprising physical measurements and natural language narratives. A generalist biomedical AI model needs to simultaneously process different modalities of data, including text and images. Therefore, training an effective generalist biomedical model requires high-quality multimodal data, such as parallel image-text pairs. Here, we present PMC-15M, a novel dataset that is two orders of magnitude larger than existing biomedical multimodal datasets such as MIMIC-CXR, and spans a diverse range of biomedical image types. PMC-15M contains 15 million biomedical image-text pairs collected from 4.4 million scientific articles. Based on PMC-15M, we have pretrained BiomedCLIP, a multimodal foundation model, with domain-specific adaptations tailored to biomedical vision-language processing. We conducted extensive experiments and ablation studies on standard biomedical imaging tasks from retrieval to classification to visual question-answering (VQA). BiomedCLIP achieved new state-of-the-art results in a wide range of standard datasets, substantially outperforming prior approaches. Intriguingly, by large-scale pretraining on diverse biomedical image types, BiomedCLIP even outperforms state-of-the-art radiology-specific models such as BioViL in radiology-specific tasks such as RSNA pneumonia detection. In summary, BiomedCLIP is a fully open-access foundation model that achieves state-of-the-art performance on various biomedical tasks, paving the way for transformative multimodal biomedical discovery and applications. We release our models at https://aka.ms/biomedclip to facilitate future research in multimodal biomedical AI.

Yu Gu, Sheng Zhang, Naoto Usuyama et al. · cambridge, microsoft-research

Large language models (LLMs), such as GPT-4, have demonstrated remarkable capabilities across a wide range of tasks, including health applications. In this paper, we study how LLMs can be used to scale biomedical knowledge curation. We find that while LLMs already possess decent competency in structuring biomedical text, by distillation into a task-specific student model through self-supervised learning, substantial gains can be attained over out-of-box LLMs, with additional advantages such as cost, efficiency, and white-box model access. We conduct a case study on adverse drug event (ADE) extraction, which is an important area for improving care. On standard ADE extraction evaluation, a GPT-3.5 distilled PubMedBERT model attained comparable accuracy as supervised state-of-the-art models without using any labeled data. Despite being over 1,000 times smaller, the distilled model outperformed its teacher GPT-3.5 by over 6 absolute points in F1 and GPT-4 by over 5 absolute points. Ablation studies on distillation model choice (e.g., PubMedBERT vs BioGPT) and ADE extraction architecture shed light on best practice for biomedical knowledge extraction. Similar gains were attained by distillation for other standard biomedical knowledge extraction tasks such as gene-disease associations and protected health information, further illustrating the promise of this approach.

Sam Preston, Mu Wei, Rajesh Rao et al. · cambridge, microsoft-research

Objective: The majority of detailed patient information in real-world data (RWD) is only consistently available in free-text clinical documents. Manual curation is expensive and time-consuming. Developing natural language processing (NLP) methods for structuring RWD is thus essential for scaling real-world evidence generation. Materials and Methods: Traditional rule-based systems are vulnerable to the prevalent linguistic variations and ambiguities in clinical text, and prior applications of machine-learning methods typically require sentence-level or report-level labeled examples that are hard to produce at scale. We propose leveraging patient-level supervision from medical registries, which are often readily available and capture key patient information, for general RWD applications. To combat the lack of sentence-level or report-level annotations, we explore advanced deep-learning methods by combining domain-specific pretraining, recurrent neural networks, and hierarchical attention. Results: We conduct an extensive study on 135,107 patients from the cancer registry of a large integrated delivery network (IDN) comprising healthcare systems in five western US states. Our deep learning methods attain test AUROC of 94-99% for key tumor attributes and comparable performance on held-out data from separate health systems and states. Discussion and Conclusion: Ablation results demonstrate clear superiority of these advanced deep-learning methods over prior approaches. Error analysis shows that our NLP system sometimes even corrects errors in registrar labels. We also conduct a preliminary investigation in accelerating registry curation and general RWD structuring via assisted curation for over 1.2 million cancer patients in this healthcare network.

Qianchu Liu, Sheng Zhang, Guanghui Qin et al. · microsoft-research

Frontier models have demonstrated remarkable capabilities in understanding and reasoning with natural-language text, but they still exhibit major competency gaps in multimodal understanding and reasoning especially in high-value verticals such as biomedicine. Medical imaging report generation is a prominent example. Supervised fine-tuning can substantially improve performance, but they are prone to overfitting to superficial boilerplate patterns. In this paper, we introduce Universal Report Generation (UniRG) as a general framework for medical imaging report generation. By leveraging reinforcement learning as a unifying mechanism to directly optimize for evaluation metrics designed for end applications, UniRG can significantly improve upon supervised fine-tuning and attain durable generalization across diverse institutions and clinical practices. We trained UniRG-CXR on publicly available chest X-ray (CXR) data and conducted a thorough evaluation in CXR report generation with rigorous evaluation scenarios. On the authoritative ReXrank benchmark, UniRG-CXR sets new overall SOTA, outperforming prior state of the art by a wide margin.

Theodore Zhengde Zhao, Sid Kiblawi, Jianwei Yang et al.

Self-supervised learning (SSL) faces a fundamental conflict between semantic understanding and image reconstruction. High-level semantic SSL (e.g., DINO) relies on global tokens that are forced to be location-invariant for augmentation alignment, a process that inherently discards the spatial coordinates required for reconstruction. Conversely, generative SSL (e.g., MAE) preserves dense feature grids for reconstruction but fails to produce high-level abstractions. We introduce STELLAR, a framework that resolves this tension by factorizing visual features into a low-rank product of semantic concepts and their spatial distributions. This disentanglement allows us to perform DINO-style augmentation alignment on the semantic tokens while maintaining the precise spatial mapping in the localization matrix necessary for pixel-level reconstruction. We demonstrate that as few as 16 sparse tokens under this factorized form are sufficient to simultaneously support high-quality reconstruction (2.60 FID) and match the semantic performance of dense backbones (79.10% ImageNet accuracy). Our results highlight STELLAR as a versatile sparse representation that bridges the gap between discriminative and generative vision by strategically separating semantic identity from spatial geometry. Code available at https://aka.ms/stellar.

Theodore Zhao, Mu Wei, J. Samuel Preston et al.

Large Language Models (LLMs) have shown impressive abilities in many applications. When a concrete and precise answer is desired, it is important to have a quantitative estimation of the potential error rate. However, this can be challenging due to the text-in-text-out nature of generative models. We present a method based on Pareto optimization that generates a risk score to estimate the probability of error in an LLM response by integrating multiple sources of information. We prove theoretically that the error estimator optimized in our framework aligns with the LLM and the information sources in an Pareto optimal manner. Experimental results show that the risk scores estimated by our method are well correlated with the true LLM error rate, thus facilitating error correction. By dynamically combining with prompting strategies such as self-verification and information retrieval, we demonstrate the proposed method can be utilized to increase the performance of an LLM, surpassing state-of-the-art task specific models.

Juan Manuel Zambrano Chaves, Shih-Cheng Huang, Yanbo Xu et al. · microsoft-research

The scaling laws and extraordinary performance of large foundation models motivate the development and utilization of such models in biomedicine. However, despite early promising results on some biomedical benchmarks, there are still major challenges that need to be addressed before these models can be used in real-world clinics. Frontier general-domain models such as GPT-4V still have significant performance gaps in multimodal biomedical applications. More importantly, less-acknowledged pragmatic issues, including accessibility, model cost, and tedious manual evaluation make it hard for clinicians to use state-of-the-art large models directly on private patient data. Here, we explore training open-source small multimodal models (SMMs) to bridge competency gaps for unmet clinical needs in radiology. To maximize data efficiency, we adopt a modular approach by incorporating state-of-the-art pre-trained models for image and text modalities, and focusing on training a lightweight adapter to ground each modality to the text embedding space, as exemplified by LLaVA-Med. For training, we assemble a large dataset of over 697 thousand radiology image-text pairs. For evaluation, we propose CheXprompt, a GPT-4-based metric for factuality evaluation, and demonstrate its parity with expert evaluation. For best practice, we conduct a systematic ablation study on various choices in data engineering and multimodal training. The resulting LlaVA-Rad (7B) model attains state-of-the-art results on standard radiology tasks such as report generation and cross-modal retrieval, even outperforming much larger models such as GPT-4V and Med-PaLM M (84B). The inference of LlaVA-Rad is fast and can be performed on a single V100 GPU in private settings, offering a promising state-of-the-art tool for real-world clinical applications.

Qianchu Liu, Sheng Zhang, Guanghui Qin et al. · microsoft-research

Recent proprietary models (e.g., o3) have begun to demonstrate strong multimodal reasoning capabilities. Yet, most existing open-source research concentrates on training text-only reasoning models, with evaluations limited to mainly mathematical and general-domain tasks. Therefore, it remains unclear how to effectively extend reasoning capabilities beyond text input and general domains. This paper explores a fundamental research question: Is reasoning generalizable across modalities and domains? Our findings support an affirmative answer: General-domain text-based post-training can enable such strong generalizable reasoning. Leveraging this finding, we introduce X-Reasoner, a vision-language model post-trained solely on general-domain text for generalizable reasoning, using a two-stage approach: an initial supervised fine-tuning phase with distilled long chain-of-thoughts, followed by reinforcement learning with verifiable rewards. Experiments show that X-Reasoner successfully transfers reasoning capabilities to both multimodal and out-of-domain settings, outperforming existing state-of-the-art models trained with in-domain and multimodal data across various general and medical benchmarks (Figure 1). Additionally, we find that X-Reasoner's performance in specialized domains can be further enhanced through continued training on domain-specific text-only data. Building upon this, we introduce X-Reasoner-Med, a medical-specialized variant that achieves new state of the art on numerous text-only and multimodal medical benchmarks.

Theodore Zhao, Yu Gu, Jianwei Yang et al.

Biomedical image analysis is fundamental for biomedical discovery in cell biology, pathology, radiology, and many other biomedical domains. Holistic image analysis comprises interdependent subtasks such as segmentation, detection, and recognition of relevant objects. Here, we propose BiomedParse, a biomedical foundation model for imaging parsing that can jointly conduct segmentation, detection, and recognition for 82 object types across 9 imaging modalities. Through joint learning, we can improve accuracy for individual tasks and enable novel applications such as segmenting all relevant objects in an image through a text prompt, rather than requiring users to laboriously specify the bounding box for each object. We leveraged readily available natural-language labels or descriptions accompanying those datasets and use GPT-4 to harmonize the noisy, unstructured text information with established biomedical object ontologies. We created a large dataset comprising over six million triples of image, segmentation mask, and textual description. On image segmentation, we showed that BiomedParse is broadly applicable, outperforming state-of-the-art methods on 102,855 test image-mask-label triples across 9 imaging modalities (everything). On object detection, which aims to locate a specific object of interest, BiomedParse again attained state-of-the-art performance, especially on objects with irregular shapes (everywhere). On object recognition, which aims to identify all objects in a given image along with their semantic types, we showed that BiomedParse can simultaneously segment and label all biomedical objects in an image (all at once). In summary, BiomedParse is an all-in-one tool for biomedical image analysis by jointly solving segmentation, detection, and recognition for all major biomedical image modalities, paving the path for efficient and accurate image-based biomedical discovery.

Ho Hin Lee, Yu Gu, Theodore Zhao et al.

Recent advancements in biomedical image analysis have been significantly driven by the Segment Anything Model (SAM). This transformative technology, originally developed for general-purpose computer vision, has found rapid application in medical image processing. Within the last year, marked by over 100 publications, SAM has demonstrated its prowess in zero-shot learning adaptations for medical imaging. The fundamental premise of SAM lies in its capability to segment or identify objects in images without prior knowledge of the object type or imaging modality. This approach aligns well with tasks achievable by the human visual system, though its application in non-biological vision contexts remains more theoretically challenging. A notable feature of SAM is its ability to adjust segmentation according to a specified resolution scale or area of interest, akin to semantic priming. This adaptability has spurred a wave of creativity and innovation in applying SAM to medical imaging. Our review focuses on the period from April 1, 2023, to September 30, 2023, a critical first six months post-initial publication. We examine the adaptations and integrations of SAM necessary to address longstanding clinical challenges, particularly in the context of 33 open datasets covered in our analysis. While SAM approaches or achieves state-of-the-art performance in numerous applications, it falls short in certain areas, such as segmentation of the carotid artery, adrenal glands, optic nerve, and mandible bone. Our survey delves into the innovative techniques where SAM's foundational approach excels and explores the core concepts in translating and applying these models effectively in diverse medical imaging scenarios.

Cliff Wong, Sam Preston, Qianchu Liu et al. · microsoft-research

A significant fraction of real-world patient information resides in unstructured clinical text. Medical abstraction extracts and normalizes key structured attributes from free-text clinical notes, which is the prerequisite for a variety of important downstream applications, including registry curation, clinical trial operations, and real-world evidence generation. Prior medical abstraction methods typically resort to building attribute-specific models, each of which requires extensive manual effort such as rule creation or supervised label annotation for the individual attribute, thus limiting scalability. In this paper, we show that existing frontier models already possess the universal abstraction capability for scaling medical abstraction to a wide range of clinical attributes. We present UniMedAbstractor (UMA), a unifying framework for zero-shot medical abstraction with a modular, customizable prompt template and the selection of any frontier large language models. Given a new attribute for abstraction, users only need to conduct lightweight prompt adaptation in UMA to adjust the specification in natural languages. Compared to traditional methods, UMA eliminates the need for attribute-specific training labels or handcrafted rules, thus substantially reducing the development time and cost. We conducted a comprehensive evaluation of UMA in oncology using a wide range of marquee attributes representing the cancer patient journey. These include relatively simple attributes typically specified within a single clinical note (e.g. performance status), as well as complex attributes requiring sophisticated reasoning across multiple notes at various time points (e.g. tumor staging). Based on a single frontier model such as GPT-4o, UMA matched or even exceeded the performance of state-of-the-art attribute-specific methods, each of which was tailored to the individual attribute.

Yu Gu, Jingjing Fu, Xiaodong Liu et al.

Large frontier models like GPT-5 now achieve top scores on medical benchmarks. But our stress tests tell a different story. Leading systems often guess correctly even when key inputs like images are removed, flip answers under trivial prompt changes, and fabricate convincing yet flawed reasoning. These aren't glitches; they expose how today's benchmarks reward test-taking tricks over medical understanding. We evaluate six flagship models across six widely used benchmarks and find that high leaderboard scores hide brittleness and shortcut learning. Through clinician-guided rubric evaluation, we show that benchmarks vary widely in what they truly measure yet are treated interchangeably, masking failure modes. We caution that medical benchmark scores do not directly reflect real-world readiness. If we want AI to earn trust in healthcare, we must demand more than leaderboard wins and must hold systems accountable for robustness, sound reasoning, and alignment with real medical demands.

Theodore Zhao, Sid Kiblawi, Naoto Usuyama et al.

Detecting and segmenting small objects, such as lung nodules and tumor lesions, remains a critical challenge in image analysis. These objects often occupy less than 0.1% of an image, making traditional transformer architectures inefficient and prone to performance degradation due to redundant attention computations on irrelevant regions. Existing sparse attention mechanisms rely on rigid hierarchical structures, which are poorly suited for detecting small, variable, and uncertain object locations. In this paper, we propose BoltzFormer, a novel transformer-based architecture designed to address these challenges through dynamic sparse attention. BoltzFormer identifies and focuses attention on relevant areas by modeling uncertainty using a Boltzmann distribution with an annealing schedule. Initially, a higher temperature allows broader area sampling in early layers, when object location uncertainty is greatest. As the temperature decreases in later layers, attention becomes more focused, enhancing efficiency and accuracy. BoltzFormer seamlessly integrates into existing transformer architectures via a modular Boltzmann attention sampling mechanism. Comprehensive evaluations on benchmark datasets demonstrate that BoltzFormer significantly improves segmentation performance for small objects while reducing attention computation by an order of magnitude compared to previous state-of-the-art methods.

Alyssa Unell, Noel C. F. Codella, Sam Preston et al.

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.

Shuhan Ding, Jingjing Fu, Yu Gu et al.

Medical image synthesis has become an essential strategy for augmenting datasets and improving model generalization in data-scarce clinical settings. However, fine-grained and controllable synthesis remains difficult due to limited high-quality annotations and domain shifts across datasets. Existing methods, often designed for natural images or well-defined tumors, struggle to generalize to chest radiographs, where disease patterns are morphologically diverse and tightly intertwined with anatomical structures. To address these challenges, we propose AURAD, a controllable radiology synthesis framework that jointly generates high-fidelity chest X-rays and pseudo semantic masks. Unlike prior approaches that rely on randomly sampled masks-limiting diversity, controllability, and clinical relevance-our method learns to generate masks that capture multi-pathology coexistence and anatomical-pathological consistency. It follows a progressive pipeline: pseudo masks are first generated from clinical prompts conditioned on anatomical structures, and then used to guide image synthesis. We also leverage pretrained expert medical models to filter outputs and ensure clinical plausibility. Beyond visual realism, the synthesized masks also serve as labels for downstream tasks such as detection and segmentation, bridging the gap between generative modeling and real-world clinical applications. Extensive experiments and blinded radiologist evaluations demonstrate the effectiveness and generalizability of our method across tasks and datasets. In particular, 78% of our synthesized images are classified as authentic by board-certified radiologists, and over 40% of predicted segmentation overlays are rated as clinically useful. All code, pre-trained models, and the synthesized dataset will be released upon publication.