Luyang Luo

Zhizhong Chai, Luyang Luo, Huangjing Lin et al.

Deep learning (DL)-based rib fracture detection has shown promise of playing an important role in preventing mortality and improving patient outcome. Normally, developing DL-based object detection models requires a huge amount of bounding box annotation. However, annotating medical data is time-consuming and expertise-demanding, making obtaining a large amount of fine-grained annotations extremely infeasible. This poses a pressing need {for} developing label-efficient detection models to alleviate radiologists' labeling burden. To tackle this challenge, the literature on object detection has witnessed an increase of weakly-supervised and semi-supervised approaches, yet still lacks a unified framework that leverages various forms of fully-labeled, weakly-labeled, and unlabeled data. In this paper, we present a novel omni-supervised object detection network, ORF-Netv2, to leverage as much available supervision as possible. Specifically, a multi-branch omni-supervised detection head is introduced with each branch trained with a specific type of supervision. A co-training-based dynamic label assignment strategy is then proposed to enable flexible and robust learning from the weakly-labeled and unlabeled data. Extensive evaluation was conducted for the proposed framework with three rib fracture datasets on both chest CT and X-ray. By leveraging all forms of supervision, ORF-Netv2 achieves mAPs of 34.7, 44.7, and 19.4 on the three datasets, respectively, surpassing the baseline detector which uses only box annotations by mAP gains of 3.8, 4.8, and 5.0, respectively. Furthermore, ORF-Netv2 consistently outperforms other competitive label-efficient methods over various scenarios, showing a promising framework for label-efficient fracture detection. The code is available at: https://github.com/zhizhongchai/ORF-Net.

Hongyi Wang, Luyang Luo, Fang Wang et al.

Whole Slide Image (WSI) classification remains a challenge due to their extremely high resolution and the absence of fine-grained labels. Presently, WSI classification is usually regarded as a Multiple Instance Learning (MIL) problem when only slide-level labels are available. MIL methods involve a patch embedding module and a bag-level classification module, but they are prohibitively expensive to be trained in an end-to-end manner. Therefore, existing methods usually train them separately, or directly skip the training of the embedder. Such schemes hinder the patch embedder's access to slide-level semantic labels, resulting in inconsistency within the entire MIL pipeline. To overcome this issue, we propose a novel framework called Iteratively Coupled MIL (ICMIL), which bridges the loss back-propagation process from the bag-level classifier to the patch embedder. In ICMIL, we use category information in the bag-level classifier to guide the patch-level fine-tuning of the patch feature extractor. The refined embedder then generates better instance representations for achieving a more accurate bag-level classifier. By coupling the patch embedder and bag classifier at a low cost, our proposed framework enables information exchange between the two modules, benefiting the entire MIL classification model. We tested our framework on two datasets using three different backbones, and our experimental results demonstrate consistent performance improvements over state-of-the-art MIL methods. The code is available at: https://github.com/Dootmaan/ICMIL.

Shu Yang, Luyang Luo, Qiong Wang et al.

Existing state-of-the-art methods for surgical phase recognition either rely on the extraction of spatial-temporal features at a short-range temporal resolution or adopt the sequential extraction of the spatial and temporal features across the entire temporal resolution. However, these methods have limitations in modeling spatial-temporal dependency and addressing spatial-temporal redundancy: 1) These methods fail to effectively model spatial-temporal dependency, due to the lack of long-range information or joint spatial-temporal modeling. 2) These methods utilize dense spatial features across the entire temporal resolution, resulting in significant spatial-temporal redundancy. In this paper, we propose the Surgical Transformer (Surgformer) to address the issues of spatial-temporal modeling and redundancy in an end-to-end manner, which employs divided spatial-temporal attention and takes a limited set of sparse frames as input. Moreover, we propose a novel Hierarchical Temporal Attention (HTA) to capture both global and local information within varied temporal resolutions from a target frame-centric perspective. Distinct from conventional temporal attention that primarily emphasizes dense long-range similarity, HTA not only captures long-term information but also considers local latent consistency among informative frames. HTA then employs pyramid feature aggregation to effectively utilize temporal information across diverse temporal resolutions, thereby enhancing the overall temporal representation. Extensive experiments on two challenging benchmark datasets verify that our proposed Surgformer performs favorably against the state-of-the-art methods. The code is released at https://github.com/isyangshu/Surgformer.

Jia-Xin Zhuang, Luyang Luo, Hao Chen · cmu

Masked autoencoder (MAE) is a promising self-supervised pre-training technique that can improve the representation learning of a neural network without human intervention. However, applying MAE directly to volumetric medical images poses two challenges: (i) a lack of global information that is crucial for understanding the clinical context of the holistic data, (ii) no guarantee of stabilizing the representations learned from randomly masked inputs. To address these limitations, we propose the \textbf{G}lobal-\textbf{L}ocal \textbf{M}asked \textbf{A}uto\textbf{E}ncoder (GL-MAE), a simple yet effective self-supervised pre-training strategy. In addition to reconstructing masked local views, as in previous methods, GL-MAE incorporates global context learning by reconstructing masked global views. Furthermore, a complete global view is integrated as an anchor to guide the reconstruction and stabilize the learning process through global-to-global consistency learning and global-to-local consistency learning. Finetuning results on multiple datasets demonstrate the superiority of our method over other state-of-the-art self-supervised algorithms, highlighting its effectiveness on versatile volumetric medical image segmentation tasks, even when annotations are scarce. Our codes and models will be released upon acceptance.

Luyang Luo, Mingxiang Wu, Mei Li et al.

Breast Magnetic Resonance Imaging (MRI) demonstrates the highest sensitivity for breast cancer detection among imaging modalities and is standard practice for high-risk women. Interpreting the multi-sequence MRI is time-consuming and prone to subjective variation. We develop a large mixture-of-modality-experts model (MOME) that integrates multiparametric MRI information within a unified structure, leveraging breast MRI scans from 5,205 female patients in China for model development and validation. MOME matches four senior radiologists' performance in identifying breast cancer and outperforms a junior radiologist. The model is able to reduce unnecessary biopsies in Breast Imaging-Reporting and Data System (BI-RADS) 4 patients, classify triple-negative breast cancer, and predict pathological complete response to neoadjuvant chemotherapy. MOME further supports inference with missing modalities and provides decision explanations by highlighting lesions and measuring modality contributions. To summarize, MOME exemplifies an accurate and robust multimodal model for noninvasive, personalized management of breast cancer patients via multiparametric MRI. Code is available at https://github.com/LLYXC/MOME/tree/main.

Luyang Luo, Dunyuan Xu, Hao Chen et al.

Deep learning models were frequently reported to learn from shortcuts like dataset biases. As deep learning is playing an increasingly important role in the modern healthcare system, it is of great need to combat shortcut learning in medical data as well as develop unbiased and trustworthy models. In this paper, we study the problem of developing debiased chest X-ray diagnosis models from the biased training data without knowing exactly the bias labels. We start with the observations that the imbalance of bias distribution is one of the key reasons causing shortcut learning, and the dataset biases are preferred by the model if they were easier to be learned than the intended features. Based on these observations, we proposed a novel algorithm, pseudo bias-balanced learning, which first captures and predicts per-sample bias labels via generalized cross entropy loss and then trains a debiased model using pseudo bias labels and bias-balanced softmax function. We constructed several chest X-ray datasets with various dataset bias situations and demonstrated with extensive experiments that our proposed method achieved consistent improvements over other state-of-the-art approaches.

Zhipeng Deng, Luyang Luo, Hao Chen

The right to be forgotten, as stated in most data regulations, poses an underexplored challenge in federated learning (FL), leading to the development of federated unlearning (FU). However, current FU approaches often face trade-offs between efficiency, model performance, forgetting efficacy, and privacy preservation. In this paper, we delve into the paradigm of Federated Client Unlearning (FCU) to guarantee a client the right to erase the contribution or the influence, introducing the first FU framework in medical imaging. In the unlearning process of a client, the proposed model-contrastive unlearning marks a pioneering step towards feature-level unlearning, and frequency-guided memory preservation ensures smooth forgetting of local knowledge while maintaining the generalizability of the trained global model, thus avoiding performance compromises and guaranteeing rapid post-training. We evaluated our FCU framework on two public medical image datasets, including Intracranial hemorrhage diagnosis and skin lesion diagnosis, demonstrating that our framework outperformed other state-of-the-art FU frameworks, with an expected speed-up of 10-15 times compared with retraining from scratch. The code and the organized datasets can be found at: https://github.com/dzp2095/FCU.

Zhipeng Deng, Luyang Luo, Hao Chen

Federated learning (FL) has been introduced to the healthcare domain as a decentralized learning paradigm that allows multiple parties to train a model collaboratively without privacy leakage. However, most previous studies have assumed that every client holds an identical label set. In reality, medical specialists tend to annotate only diseases within their area of expertise or interest. This implies that label sets in each client can be different and even disjoint. In this paper, we propose the framework FedLSM to solve the problem of Label Set Mismatch. FedLSM adopts different training strategies on data with different uncertainty levels to efficiently utilize unlabeled or partially labeled data as well as class-wise adaptive aggregation in the classification layer to avoid inaccurate aggregation when clients have missing labels. We evaluated FedLSM on two public real-world medical image datasets, including chest X-ray (CXR) diagnosis with 112,120 CXR images and skin lesion diagnosis with 10,015 dermoscopy images, and showed that it significantly outperformed other state-of-the-art FL algorithms. The code can be found at https://github.com/dzp2095/FedLSM.

Zhizhong Chai, Huangjing Lin, Luyang Luo et al.

Most of the existing object detection works are based on the bounding box annotation: each object has a precise annotated box. However, for rib fractures, the bounding box annotation is very labor-intensive and time-consuming because radiologists need to investigate and annotate the rib fractures on a slice-by-slice basis. Although a few studies have proposed weakly-supervised methods or semi-supervised methods, they could not handle different forms of supervision simultaneously. In this paper, we proposed a novel omni-supervised object detection network, which can exploit multiple different forms of annotated data to further improve the detection performance. Specifically, the proposed network contains an omni-supervised detection head, in which each form of annotation data corresponds to a unique classification branch. Furthermore, we proposed a dynamic label assignment strategy for different annotated forms of data to facilitate better learning for each branch. Moreover, we also design a confidence-aware classification loss to emphasize the samples with high confidence and further improve the model's performance. Extensive experiments conducted on the testing dataset show our proposed method outperforms other state-of-the-art approaches consistently, demonstrating the efficacy of deep omni-supervised learning on improving rib fracture detection performance.

Luyang Luo, Xi Wang, Yi Lin et al.

Breast cancer has reached the highest incidence rate worldwide among all malignancies since 2020. Breast imaging plays a significant role in early diagnosis and intervention to improve the outcome of breast cancer patients. In the past decade, deep learning has shown remarkable progress in breast cancer imaging analysis, holding great promise in interpreting the rich information and complex context of breast imaging modalities. Considering the rapid improvement in deep learning technology and the increasing severity of breast cancer, it is critical to summarize past progress and identify future challenges to be addressed. This paper provides an extensive review of deep learning-based breast cancer imaging research, covering studies on mammogram, ultrasound, magnetic resonance imaging, and digital pathology images over the past decade. The major deep learning methods and applications on imaging-based screening, diagnosis, treatment response prediction, and prognosis are elaborated and discussed. Drawn from the findings of this survey, we present a comprehensive discussion of the challenges and potential avenues for future research in deep learning-based breast cancer imaging.

Jiaxin Zhuang, Luyang Luo, Zhixuan Chen et al.

Deep-learning (DL) based methods are playing an important role in the task of abdominal organs and tumors segmentation in CT scans. However, the large requirements of annotated datasets heavily limit its development. The FLARE23 challenge provides a large-scale dataset with both partially and fully annotated data, which also focuses on both segmentation accuracy and computational efficiency. In this study, we propose to use the strategy of Semi-Supervised Learning (SSL) and iterative pseudo labeling to address FLARE23. Initially, a deep model (nn-UNet) trained on datasets with complete organ annotations (about 220 scans) generates pseudo labels for the whole dataset. These pseudo labels are then employed to train a more powerful segmentation model. Employing the FLARE23 dataset, our approach achieves an average DSC score of 89.63% for organs and 46.07% for tumors on online validation leaderboard. For organ segmentation, We obtain 0.9007\% DSC and 0.9493\% NSD. For tumor segmentation, we obtain 0.3785% DSC and 0.2842% NSD. Our code is available at https://github.com/USTguy/Flare23.

Yifeng Wang, Luyang Luo, Mingxiang Wu et al.

Collecting annotations from multiple independent sources could mitigate the impact of potential noises and biases from a single source, which is a common practice in medical image segmentation. Learning segmentation networks from multi-source annotations remains a challenge due to the uncertainties brought by the variance of annotations and the quality of images. In this paper, we propose an Uncertainty-guided Multi-source Annotation Network (UMA-Net), which guides the training process by uncertainty estimation at both the pixel and the image levels. First, we developed the annotation uncertainty estimation module (AUEM) to learn the pixel-wise uncertainty of each annotation, which then guided the network to learn from reliable pixels by weighted segmentation loss. Second, a quality assessment module (QAM) was proposed to assess the image-level quality of the input samples based on the former assessed annotation uncertainties. Importantly, we introduced an auxiliary predictor to learn from the low-quality samples instead of discarding them, which ensured the preservation of their representation knowledge in the backbone without directly accumulating errors within the primary predictor. Extensive experiments demonstrated the effectiveness and feasibility of our proposed UMA-Net on various datasets, including 2D chest X-ray segmentation, fundus image segmentation, and 3D breast DCE-MRI segmentation.

Cheng Jin, Zhengrui Guo, Yi Lin et al.

Deep learning has significantly advanced medical imaging analysis (MIA), achieving state-of-the-art performance across diverse clinical tasks. However, its success largely depends on large-scale, high-quality labeled datasets, which are costly and time-consuming to obtain due to the need for expert annotation. To mitigate this limitation, label-efficient deep learning methods have emerged to improve model performance under limited supervision by leveraging labeled, unlabeled, and weakly labeled data. In this survey, we systematically review over 350 peer-reviewed studies and present a comprehensive taxonomy of label-efficient learning methods in MIA. These methods are categorized into four labeling paradigms: no label, insufficient label, inexact label, and label refinement. For each category, we analyze representative techniques across imaging modalities and clinical applications, highlighting shared methodological principles and task-specific adaptations. We also examine the growing role of health foundation models (HFMs) in enabling label-efficient learning through large-scale pre-training and transfer learning, enhancing the use of limited annotations in downstream tasks. Finally, we identify current challenges and future directions to facilitate the translation of label-efficient learning from research promise to everyday clinical care.

Shu Yang, Zhiyuan Cai, Luyang Luo et al.

Capitalizing on image-level pre-trained models for various downstream tasks has recently emerged with promising performance. However, the paradigm of "image pre-training followed by video fine-tuning" for high-dimensional video data inevitably poses significant performance bottlenecks. Furthermore, in the medical domain, many surgical video tasks encounter additional challenges posed by the limited availability of video data and the necessity for comprehensive spatial-temporal modeling. Recently, Parameter-Efficient Image-to-Video Transfer Learning has emerged as an efficient and effective paradigm for video action recognition tasks, which employs image-level pre-trained models with promising feature transferability and involves cross-modality temporal modeling with minimal fine-tuning. Nevertheless, the effectiveness and generalizability of this paradigm within intricate surgical domain remain unexplored. In this paper, we delve into a novel problem of efficiently adapting image-level pre-trained models to specialize in fine-grained surgical phase recognition, termed as Parameter-Efficient Image-to-Surgical-Video Transfer Learning. Firstly, we develop a parameter-efficient transfer learning benchmark SurgPETL for surgical phase recognition, and conduct extensive experiments with three advanced methods based on ViTs of two distinct scales pre-trained on five large-scale natural and medical datasets. Then, we introduce the Spatial-Temporal Adaptation module, integrating a standard spatial adapter with a novel temporal adapter to capture detailed spatial features and establish connections across temporal sequences for robust spatial-temporal modeling. Extensive experiments on three challenging datasets spanning various surgical procedures demonstrate the effectiveness of SurgPETL with STA.

Sunan He, Yuxiang Nie, Hongmei Wang et al.

Generalist foundation models (GFMs) are renowned for their exceptional capability and flexibility in effectively generalizing across diverse tasks and modalities. In the field of medicine, while GFMs exhibit superior generalizability based on their extensive intrinsic knowledge as well as proficiency in instruction following and in-context learning, specialist models excel in precision due to their domain knowledge. In this work, for the first time, we explore the synergy between the GFM and specialist models, to enable precise medical image analysis on a broader scope. Specifically, we propose a cooperative framework, Generalist-Specialist Collaboration (GSCo), which consists of two stages, namely the construction of GFM and specialists, and collaborative inference on downstream tasks. In the construction stage, we develop MedDr, the largest open-source GFM tailored for medicine, showcasing exceptional instruction-following and in-context learning capabilities. Meanwhile, a series of lightweight specialists are crafted for downstream tasks with low computational cost. In the collaborative inference stage, we introduce two cooperative mechanisms, Mixture-of-Expert Diagnosis and Retrieval-Augmented Diagnosis, to harvest the generalist's in-context learning abilities alongside the specialists' domain expertise. For a comprehensive evaluation, we curate a large-scale benchmark featuring 28 datasets and about 250,000 images. Extensive results demonstrate that MedDr consistently outperforms state-of-the-art GFMs on downstream datasets. Furthermore, GSCo exceeds both GFMs and specialists across all out-of-domain disease diagnosis datasets. These findings indicate a significant paradigm shift in the application of GFMs, transitioning from separate models for specific tasks to a collaborative approach between GFMs and specialists, thereby advancing the frontiers of generalizable AI in medicine.

Cheng Jin, Luyang Luo, Huangjing Lin et al.

Fine-grained classification of whole slide images (WSIs) is essential in precision oncology, enabling precise cancer diagnosis and personalized treatment strategies. The core of this task involves distinguishing subtle morphological variations within the same broad category of gigapixel-resolution images, which presents a significant challenge. While the multi-instance learning (MIL) paradigm alleviates the computational burden of WSIs, existing MIL methods often overlook hierarchical label correlations, treating fine-grained classification as a flat multi-class classification task. To overcome these limitations, we introduce a novel hierarchical multi-instance learning (HMIL) framework. By facilitating on the hierarchical alignment of inherent relationships between different hierarchy of labels at instance and bag level, our approach provides a more structured and informative learning process. Specifically, HMIL incorporates a class-wise attention mechanism that aligns hierarchical information at both the instance and bag levels. Furthermore, we introduce supervised contrastive learning to enhance the discriminative capability for fine-grained classification and a curriculum-based dynamic weighting module to adaptively balance the hierarchical feature during training. Extensive experiments on our large-scale cytology cervical cancer (CCC) dataset and two public histology datasets, BRACS and PANDA, demonstrate the state-of-the-art class-wise and overall performance of our HMIL framework. Our source code is available at https://github.com/ChengJin-git/HMIL.

Mohammed Baharoon, Luyang Luo, Michael Moritz et al.

We introduce ReXGroundingCT, the first publicly available dataset linking free-text findings to pixel-level 3D segmentations in chest CT scans. The dataset includes 3,142 non-contrast chest CT scans paired with standardized radiology reports from CT-RATE. Construction followed a structured three-stage pipeline. First, GPT-4 was used to extract and standardize findings, descriptors, and metadata from reports originally written in Turkish and machine-translated into English. Second, GPT-4o-mini categorized each finding into a hierarchical ontology of lung and pleural abnormalities. Third, 3D annotations were produced for all CT volumes: the training set was quality-assured by board-certified radiologists, and the validation and test sets were fully annotated by board-certified radiologists. Additionally, a complementary chain-of-thought dataset was created to provide step-by-step hierarchical anatomical reasoning for localizing findings within the CT volume, using GPT-4o and localization coordinates derived from organ segmentation models. ReXGroundingCT contains 16,301 annotated entities across 8,028 text-to-3D-segmentation pairs, covering diverse radiological patterns from 3,142 non-contrast CT scans. About 79% of findings are focal abnormalities and 21% are non-focal. The dataset includes a public validation set of 50 cases and a private test set of 100 cases, both annotated by board-certified radiologists. The dataset establishes a foundation for enabling free-text finding segmentation and grounded radiology report generation in CT imaging. Model performance on the private test set is hosted on a public leaderboard at https://rexrank.ai/ReXGroundingCT. The dataset is available at https://huggingface.co/datasets/rajpurkarlab/ReXGroundingCT.

Sraavya Sambara, Sung Eun Kim, Xiaoman Zhang et al.

Current Vision-Language Models (VLMs) struggle to ground anatomical regions in 3D medical images and reason about them in a step-by-step manner, a key requirement of real-world diagnostic assessment. This ability is essential for aligning model outputs with the diagnostic workflows clinicians use in practice, enabling trustworthy clinician-AI collaboration. Existing 3D datasets provide localization labels, but none support this "grounded reasoning" ability. To address this gap, we introduce 3DReasonKnee, the first 3D grounded reasoning dataset for medical images, which provides 494k high-quality quintuples derived from 7,970 3D knee MRI volumes. Each quintuple includes: (1) the 3D MRI volume, (2) a diagnostic question targeting a specific anatomical region (3) a 3D bounding box localizing the relevant anatomical structures, (4) clinician-generated diagnostic reasoning steps that explicitly detail the 3D reasoning process, and (5) structured severity assessments for the relevant anatomical region. The creation and validation of 3DReasonKnee, involving over 450 hours of expert clinician time for manually segmenting MRIs and generating reasoning chains, ensures its superior quality and clinical relevance. We establish ReasonKnee-Bench to evaluate localization and diagnostic accuracy, providing insight into VLM ability to perform grounding and severity assessment across anatomical regions and diagnostic inquiries. We benchmark five state-of-the-art VLMs, providing baseline performance for ReasonKnee-Bench. By providing this unique resource of expert-annotated 3D reasoning pathways, 3DReasonKnee serves as a repository of orthopedic surgeons' diagnostic expertise and offers a vital testbed for advancing multimodal medical AI systems towards 3D, clinically aligned, localized decision-making capabilities. The dataset can be found in: https://huggingface.co/datasets/rajpurkarlab/3DReasonKnee

Zhixuan Chen, Luyang Luo, Yequan Bie et al.

Medical report generation has achieved remarkable advancements yet has still been faced with several challenges. First, the inherent imbalance in the distribution of normal and abnormal cases may lead models to exhibit a biased focus on normal samples, resulting in unreliable diagnoses. Second, the frequent occurrence of common template sentences in the reports may overwhelm the critical abnormal information. Moreover, existing works focus on 2D chest X-rays, leaving CT report generation underexplored due to the high-dimensional nature of CT images and the limited availability of CT-report pairs. Recently, LLM has shown a great ability to generate reliable answers with appropriate prompts, which shed light on addressing the aforementioned challenges. In this paper, we propose Dia-LLaMA, a framework to adapt the LLaMA2-7B for CT report generation by incorporating diagnostic information as guidance prompts. Considering the high dimension of CT, we leverage a pre-trained ViT3D with perceiver to extract the visual information. To tailor the LLM for report generation and emphasize abnormality, we extract additional diagnostic information by referring to a disease prototype memory bank, which is updated during training to capture common disease representations. Furthermore, we introduce disease-aware attention to enable the model to adjust attention for different diseases. Experiments on the chest CT dataset demonstrated that our proposed method outperformed previous methods and achieved state-of-the-art on both clinical efficacy performance and natural language generation metrics. The code will be made publically available.

Wenhui Lei, Hanyu Chen, Zitian Zhang et al.

AI-assisted imaging made substantial advances in tumor diagnosis and management. However, a major barrier to developing robust oncology foundation models is the scarcity of large-scale, high-quality annotated datasets, which are limited by privacy restrictions and the high cost of manual labeling. To address this gap, we present PASTA, a pan-tumor radiology foundation model built on PASTA-Gen, a synthetic data framework that generated 30,000 3D CT scans with pixel-level lesion masks and structured reports of tumors across ten organ systems. Leveraging this resource, PASTA achieves state-of-the-art performance on 45 of 46 oncology tasks, including non-contrast CT tumor screening, lesion segmentation, structured reporting, tumor staging, survival prediction, and MRI-modality transfer. To assess clinical applicability, we developed PASTA-AID, a clinical decision support system, and ran a retrospective simulated clinical trial across two scenarios. For pan-tumor screening on plain CT with fixed reading time, PASTA-AID increased radiologists' throughput by 11.1-25.1% and improved sensitivity by 17.0-31.4% and precision by 10.5-24.9%; additionally, in a diagnosis-aid workflow, it reduced segmentation time by up to 78.2% and reporting time by up to 36.5%. Beyond gains in accuracy and efficiency, PASTA-AID narrowed the expertise gap, enabling less-experienced radiologists to approach expert-level performance. Together, this work establishes an end-to-end, synthetic data-driven pipeline spanning data generation, model development, and clinical validation, thereby demonstrating substantial potential for pan-tumor research and clinical translation.

Linshan Wu, Jiaxin Zhuang, Yanning Zhou et al.

Tumor is a leading cause of death worldwide, with an estimated 10 million deaths attributed to tumor-related diseases every year. AI-driven tumor recognition unlocks new possibilities for more precise and intelligent tumor screening and diagnosis. However, the progress is heavily hampered by the scarcity of annotated datasets, which demands extensive annotation efforts by radiologists. To tackle this challenge, we introduce FreeTumor, an innovative Generative AI (GAI) framework to enable large-scale tumor synthesis for mitigating data scarcity. Specifically, FreeTumor effectively leverages a combination of limited labeled data and large-scale unlabeled data for tumor synthesis training. Unleashing the power of large-scale data, FreeTumor is capable of synthesizing a large number of realistic tumors on images for augmenting training datasets. To this end, we create the largest training dataset for tumor synthesis and recognition by curating 161,310 publicly available Computed Tomography (CT) volumes from 33 sources, with only 2.3% containing annotated tumors. To validate the fidelity of synthetic tumors, we engaged 13 board-certified radiologists in a Visual Turing Test to discern between synthetic and real tumors. Rigorous clinician evaluation validates the high quality of our synthetic tumors, as they achieved only 51.1% sensitivity and 60.8% accuracy in distinguishing our synthetic tumors from real ones. Through high-quality tumor synthesis, FreeTumor scales up the recognition training datasets by over 40 times, showcasing a notable superiority over state-of-the-art AI methods including various synthesis methods and foundation models. These findings indicate promising prospects of FreeTumor in clinical applications, potentially advancing tumor treatments and improving the survival rates of patients.

Yuxiang Nie, Sunan He, Yequan Bie et al.

The clinical adoption of artificial intelligence (AI) in medical imaging requires models that are both diagnostically accurate and interpretable to clinicians. While current multimodal biomedical foundation models prioritize performance, their black-box nature hinders explaining the decision-making process in clinically meaningful concepts. Here, we present ConceptCLIP, the first explainable biomedical foundation model that achieves state-of-the-art diagnostic accuracy while delivering human-interpretable explanations across diverse imaging modalities. We curate MedConcept-23M, the largest pre-training dataset comprising 23 million image-text-concept triplets across diverse medical modalities, where clinical concepts are derived from the Unified Medical Language System. Leveraging this dataset, we develop ConceptCLIP through a novel dual-alignment approach that simultaneously learns global image-text representations and fine-grained region-concept associations for precise and interpretable medical image analysis. We curate the most extensive evaluation benchmark for multimodal biomedical foundation models, covering 52 clinical tasks spanning 10 imaging modalities. Extensive experiments demonstrate that ConceptCLIP outperforms existing state-of-the-art multimodal biomedical foundation models. Importantly, ConceptCLIP demonstrates superior diagnostic performance while providing human-understandable explanations validated by clinical experts. As the first precise and interpretable biomedical foundation model, ConceptCLIP represents a critical milestone toward the widespread clinical adoption of AI, thereby advancing trustworthy AI in medicine.

Luyang Luo, Xin Huang, Minghao Wang et al.

Deep learning could be prone to learning shortcuts raised by dataset bias and result in inaccurate, unreliable, and unfair models, which impedes its adoption in real-world clinical applications. Despite its significance, there is a dearth of research in the medical image classification domain to address dataset bias. Furthermore, the bias labels are often agnostic, as identifying biases can be laborious and depend on post-hoc interpretation. This paper proposes learning Adaptive Agreement from a Biased Council (Ada-ABC), a debiasing framework that does not rely on explicit bias labels to tackle dataset bias in medical images. Ada-ABC develops a biased council consisting of multiple classifiers optimized with generalized cross entropy loss to learn the dataset bias. A debiasing model is then simultaneously trained under the guidance of the biased council. Specifically, the debiasing model is required to learn adaptive agreement with the biased council by agreeing on the correctly predicted samples and disagreeing on the wrongly predicted samples by the biased council. In this way, the debiasing model could learn the target attribute on the samples without spurious correlations while also avoiding ignoring the rich information in samples with spurious correlations. We theoretically demonstrated that the debiasing model could learn the target features when the biased model successfully captures dataset bias. Moreover, to our best knowledge, we constructed the first medical debiasing benchmark from four datasets containing seven different bias scenarios. Our extensive experiments practically showed that our proposed Ada-ABC outperformed competitive approaches, verifying its effectiveness in mitigating dataset bias for medical image classification. The codes and organized benchmark datasets will be made publicly available.

Linshan Wu, Yuxiang Nie, Sunan He et al.

The integration of AI-assisted biomedical image analysis into clinical practice demands AI-generated findings that are not only accurate but also interpretable to clinicians. However, existing biomedical AI models generally lack the ability to simultaneously generate diagnostic findings and localize corresponding biomedical objects. This limitation makes it challenging for clinicians to correlate AI-generated findings with visual evidence (e.g., tiny lesions) in images and interpret the results of AI models. To address this challenge, we introduce UniBiomed, the first universal foundation model for grounded biomedical image interpretation, which is capable of generating accurate diagnostic findings and simultaneously segmenting the corresponding biomedical targets. UniBiomed is based on a novel integration of Multi-modal Large Language Model and Segment Anything Model, which can effectively unify diverse biomedical tasks in universal training for advancing grounded interpretation. To develop UniBiomed, we curate a large-scale dataset comprising over 27 million triplets of images, region annotations, and text descriptions across ten biomedical imaging modalities. Extensive validation on 70 internal and 14 external datasets demonstrated the state-of-the-art performance of UniBiomed in diverse biomedical tasks, including image segmentation, disease recognition, region-aware diagnosis, vision question answering, and report generation. In summary, UniBiomed is a powerful and versatile biomedical foundation model, unlocking the untapped grounded interpretation capability for optimizing AI-assisted biomedical image analysis.

Hao Jiang, Cheng Jin, Huangjing Lin et al.

Cervical cancer is a leading malignancy in female reproductive system. While AI-assisted cytology offers a cost-effective and non-invasive screening solution, current systems struggle with generalizability in complex clinical scenarios. To address this issue, we introduced Smart-CCS, a generalizable Cervical Cancer Screening paradigm based on pretraining and adaptation to create robust and generalizable screening systems. To develop and validate Smart-CCS, we first curated a large-scale, multi-center dataset named CCS-127K, which comprises a total of 127,471 cervical cytology whole-slide images collected from 48 medical centers. By leveraging large-scale self-supervised pretraining, our CCS models are equipped with strong generalization capability, potentially generalizing across diverse scenarios. Then, we incorporated test-time adaptation to specifically optimize the trained CCS model for complex clinical settings, which adapts and refines predictions, improving real-world applicability. We conducted large-scale system evaluation among various cohorts. In retrospective cohorts, Smart-CCS achieved an overall area under the curve (AUC) value of 0.965 and sensitivity of 0.913 for cancer screening on 11 internal test datasets. In external testing, system performance maintained high at 0.950 AUC across 6 independent test datasets. In prospective cohorts, our Smart-CCS achieved AUCs of 0.947, 0.924, and 0.986 in three prospective centers, respectively. Moreover, the system demonstrated superior sensitivity in diagnosing cervical cancer, confirming the accuracy of our cancer screening results by using histology findings for validation. Interpretability analysis with cell and slide predictions further indicated that the system's decision-making aligns with clinical practice. Smart-CCS represents a significant advancement in cancer screening across diverse clinical contexts.

Cheng Jin, Fengtao Zhou, Yunfang Yu et al.

Precision oncology requires accurate molecular insights, yet obtaining these directly from genomics is costly and time-consuming for broad clinical use. Predicting complex molecular features and patient prognosis directly from routine whole-slide images (WSI) remains a major challenge for current deep learning methods. Here we introduce PathLUPI, which uses transcriptomic privileged information during training to extract genome-anchored histological embeddings, enabling effective molecular prediction using only WSIs at inference. Through extensive evaluation across 49 molecular oncology tasks using 11,257 cases among 20 cohorts, PathLUPI demonstrated superior performance compared to conventional methods trained solely on WSIs. Crucially, it achieves AUC $\geq$ 0.80 in 14 of the biomarker prediction and molecular subtyping tasks and C-index $\geq$ 0.70 in survival cohorts of 5 major cancer types. Moreover, PathLUPI embeddings reveal distinct cellular morphological signatures associated with specific genotypes and related biological pathways within WSIs. By effectively encoding molecular context to refine WSI representations, PathLUPI overcomes a key limitation of existing models and offers a novel strategy to bridge molecular insights with routine pathology workflows for wider clinical application.

Julian Acosta, Scott Adams, Julius Kernbach et al.

We developed a voice-driven artificial intelligence (AI) system that guides anyone - from paramedics to family members - through expert-level stroke evaluations using natural conversation, while also enabling smartphone video capture of key examination components for documentation and potential expert review. This addresses a critical gap in emergency care: current stroke recognition by first responders is inconsistent and often inaccurate, with sensitivity for stroke detection as low as 58%, causing life-threatening delays in treatment. Three non-medical volunteers used our AI system to assess ten simulated stroke patients, including cases with likely large vessel occlusion (LVO) strokes and stroke-like conditions, while we measured diagnostic accuracy, completion times, user confidence, and expert physician review of the AI-generated reports. The AI system correctly identified 84% of individual stroke signs and detected 75% of likely LVOs, completing evaluations in just over 6 minutes. Users reported high confidence (median 4.5/5) and ease of use (mean 4.67/5). The system successfully identified 86% of actual strokes but also incorrectly flagged 2 of 3 non-stroke cases as strokes. When an expert physician reviewed the AI reports with videos, they identified the correct diagnosis in 100% of cases, but felt confident enough to make preliminary treatment decisions in only 40% of cases due to observed AI errors including incorrect scoring and false information. While the current system's limitations necessitate human oversight, ongoing rapid advancements in speech-to-speech AI models suggest that future versions are poised to enable highly accurate assessments. Achieving human-level voice interaction could transform emergency medical care, putting expert-informed assessment capabilities in everyone's hands.

Huajun Zhou, Fengtao Zhou, Chenyu Zhao et al.

The essence of precision oncology lies in its commitment to tailor targeted treatments and care measures to each patient based on the individual characteristics of the tumor. The inherent heterogeneity of tumors necessitates gathering information from diverse data sources to provide valuable insights from various perspectives, fostering a holistic comprehension of the tumor. Over the past decade, multimodal data integration technology for precision oncology has made significant strides, showcasing remarkable progress in understanding the intricate details within heterogeneous data modalities. These strides have exhibited tremendous potential for improving clinical decision-making and model interpretation, contributing to the advancement of cancer care and treatment. Given the rapid progress that has been achieved, we provide a comprehensive overview of about 300 papers detailing cutting-edge multimodal data integration techniques in precision oncology. In addition, we conclude the primary clinical applications that have reaped significant benefits, including early assessment, diagnosis, prognosis, and biomarker discovery. Finally, derived from the findings of this survey, we present an in-depth analysis that explores the pivotal challenges and reveals essential pathways for future research in the field of multimodal data integration for precision oncology.

Yequan Bie, Luyang Luo, Zhixuan Chen et al.

Utilizing potent representations of the large vision-language models (VLMs) to accomplish various downstream tasks has attracted increasing attention. Within this research field, soft prompt learning has become a representative approach for efficiently adapting VLMs such as CLIP, to tasks like image classification. However, most existing prompt learning methods learn text tokens that are unexplainable, which cannot satisfy the stringent interpretability requirements of Explainable Artificial Intelligence (XAI) in high-stakes scenarios like healthcare. To address this issue, we propose a novel explainable prompt learning framework that leverages medical knowledge by aligning the semantics of images, learnable prompts, and clinical concept-driven prompts at multiple granularities. Moreover, our framework addresses the lack of valuable concept annotations by eliciting knowledge from large language models and offers both visual and textual explanations for the prompts. Extensive experiments and explainability analyses conducted on various datasets, with and without concept labels, demonstrate that our method simultaneously achieves superior diagnostic performance, flexibility, and interpretability, shedding light on the effectiveness of foundation models in facilitating XAI. The code will be made publically available.

Yequan Bie, Luyang Luo, Hao Chen

Black-box deep learning approaches have showcased significant potential in the realm of medical image analysis. However, the stringent trustworthiness requirements intrinsic to the medical field have catalyzed research into the utilization of Explainable Artificial Intelligence (XAI), with a particular focus on concept-based methods. Existing concept-based methods predominantly apply concept annotations from a single perspective (e.g., global level), neglecting the nuanced semantic relationships between sub-regions and concepts embedded within medical images. This leads to underutilization of the valuable medical information and may cause models to fall short in harmoniously balancing interpretability and performance when employing inherently interpretable architectures such as Concept Bottlenecks. To mitigate these shortcomings, we propose a multi-modal explainable disease diagnosis framework that meticulously aligns medical images and clinical-related concepts semantically at multiple strata, encompassing the image level, token level, and concept level. Moreover, our method allows for model intervention and offers both textual and visual explanations in terms of human-interpretable concepts. Experimental results on three skin image datasets demonstrate that our method, while preserving model interpretability, attains high performance and label efficiency for concept detection and disease diagnosis.

Yanwen Li, Luyang Luo, Huangjing Lin et al.

Convolutional Neural Networks (CNNs) have shown remarkable progress in medical image segmentation. However, lesion segmentation remains a challenge to state-of-the-art CNN-based algorithms due to the variance in scales and shapes. On the one hand, tiny lesions are hard to be delineated precisely from the medical images which are often of low resolutions. On the other hand, segmenting large-size lesions requires large receptive fields, which exacerbates the first challenge. In this paper, we present a scale-aware super-resolution network to adaptively segment lesions of various sizes from the low-resolution medical images. Our proposed network contains dual branches to simultaneously conduct lesion mask super-resolution and lesion image super-resolution. The image super-resolution branch will provide more detailed features for the segmentation branch, i.e., the mask super-resolution branch, for fine-grained segmentation. Meanwhile, we introduce scale-aware dilated convolution blocks into the multi-task decoders to adaptively adjust the receptive fields of the convolutional kernels according to the lesion sizes. To guide the segmentation branch to learn from richer high-resolution features, we propose a feature affinity module and a scale affinity module to enhance the multi-task learning of the dual branches. On multiple challenging lesion segmentation datasets, our proposed network achieved consistent improvements compared to other state-of-the-art methods.

Luyang Luo, Hao Chen, Yongjie Xiao et al.

Two DL models were developed using radiograph-level annotations (yes or no disease) and fine-grained lesion-level annotations (lesion bounding boxes), respectively named CheXNet and CheXDet. The models' internal classification performance and lesion localization performance were compared on a testing set (n=2,922), external classification performance was compared on NIH-Google (n=4,376) and PadChest (n=24,536) datasets, and external lesion localization performance was compared on NIH-ChestX-ray14 dataset (n=880). The models were also compared to radiologists on a subset of the internal testing set (n=496). Given sufficient training data, both models performed comparably to radiologists. CheXDet achieved significant improvement for external classification, such as in classifying fracture on NIH-Google (CheXDet area under the ROC curve [AUC]: 0.67, CheXNet AUC: 0.51; p<.001) and PadChest (CheXDet AUC: 0.78, CheXNet AUC: 0.55; p<.001). CheXDet achieved higher lesion detection performance than CheXNet for most abnormalities on all datasets, such as in detecting pneumothorax on the internal set (CheXDet jacknife alternative free-response ROC-figure of merit [JAFROC-FOM]: 0.87, CheXNet JAFROC-FOM: 0.13; p<.001) and NIH-ChestX-ray14 (CheXDet JAFROC-FOM: 0.55, CheXNet JAFROC-FOM: 0.04; p<.001). To summarize, fine-grained annotations overcame shortcut learning and enabled DL models to identify correct lesion patterns, improving the models' generalizability.

Yanwen Li, Luyang Luo, Huangjing Lin et al.

The novel coronavirus disease 2019 (COVID-19) characterized by atypical pneumonia has caused millions of deaths worldwide. Automatically segmenting lesions from chest Computed Tomography (CT) is a promising way to assist doctors in COVID-19 screening, treatment planning, and follow-up monitoring. However, voxel-wise annotations are extremely expert-demanding and scarce, especially when it comes to novel diseases, while an abundance of unlabeled data could be available. To tackle the challenge of limited annotations, in this paper, we propose an uncertainty-guided dual-consistency learning network (UDC-Net) for semi-supervised COVID-19 lesion segmentation from CT images. Specifically, we present a dual-consistency learning scheme that simultaneously imposes image transformation equivalence and feature perturbation invariance to effectively harness the knowledge from unlabeled data. We then quantify the segmentation uncertainty in two forms and employ them together to guide the consistency regularization for more reliable unsupervised learning. Extensive experiments showed that our proposed UDC-Net improves the fully supervised method by 6.3% in Dice and outperforms other competitive semi-supervised approaches by significant margins, demonstrating high potential in real-world clinical practice.

Luyang Luo, Hao Chen, Yanning Zhou et al.

Chest X-ray (CXR) is the most typical diagnostic X-ray examination for screening various thoracic diseases. Automatically localizing lesions from CXR is promising for alleviating radiologists' reading burden. However, CXR datasets are often with massive image-level annotations and scarce lesion-level annotations, and more often, without annotations. Thus far, unifying different supervision granularities to develop thoracic disease detection algorithms has not been comprehensively addressed. In this paper, we present OXnet, the first deep omni-supervised thoracic disease detection network to our best knowledge that uses as much available supervision as possible for CXR diagnosis. We first introduce supervised learning via a one-stage detection model. Then, we inject a global classification head to the detection model and propose dual attention alignment to guide the global gradient to the local detection branch, which enables learning lesion detection from image-level annotations. We also impose intra-class compactness and inter-class separability with global prototype alignment to further enhance the global information learning. Moreover, we leverage a soft focal loss to distill the soft pseudo-labels of unlabeled data generated by a teacher model. Extensive experiments on a large-scale chest X-ray dataset show the proposed OXnet outperforms competitive methods with significant margins. Further, we investigate omni-supervision under various annotation granularities and corroborate OXnet is a promising choice to mitigate the plight of annotation shortage for medical image diagnosis.

Luyang Luo, Lequan Yu, Hao Chen et al.

Deep learning approaches have demonstrated remarkable progress in automatic Chest X-ray analysis. The data-driven feature of deep models requires training data to cover a large distribution. Therefore, it is substantial to integrate knowledge from multiple datasets, especially for medical images. However, learning a disease classification model with extra Chest X-ray (CXR) data is yet challenging. Recent researches have demonstrated that performance bottleneck exists in joint training on different CXR datasets, and few made efforts to address the obstacle. In this paper, we argue that incorporating an external CXR dataset leads to imperfect training data, which raises the challenges. Specifically, the imperfect data is in two folds: domain discrepancy, as the image appearances vary across datasets; and label discrepancy, as different datasets are partially labeled. To this end, we formulate the multi-label thoracic disease classification problem as weighted independent binary tasks according to the categories. For common categories shared across domains, we adopt task-specific adversarial training to alleviate the feature differences. For categories existing in a single dataset, we present uncertainty-aware temporal ensembling of model predictions to mine the information from the missing labels further. In this way, our framework simultaneously models and tackles the domain and label discrepancies, enabling superior knowledge mining ability. We conduct extensive experiments on three datasets with more than 360,000 Chest X-ray images. Our method outperforms other competing models and sets state-of-the-art performance on the official NIH test set with 0.8349 AUC, demonstrating its effectiveness of utilizing the external dataset to improve the internal classification.

Quande Liu, Lequan Yu, Luyang Luo et al.

Training deep neural networks usually requires a large amount of labeled data to obtain good performance. However, in medical image analysis, obtaining high-quality labels for the data is laborious and expensive, as accurately annotating medical images demands expertise knowledge of the clinicians. In this paper, we present a novel relation-driven semi-supervised framework for medical image classification. It is a consistency-based method which exploits the unlabeled data by encouraging the prediction consistency of given input under perturbations, and leverages a self-ensembling model to produce high-quality consistency targets for the unlabeled data. Considering that human diagnosis often refers to previous analogous cases to make reliable decisions, we introduce a novel sample relation consistency (SRC) paradigm to effectively exploit unlabeled data by modeling the relationship information among different samples. Superior to existing consistency-based methods which simply enforce consistency of individual predictions, our framework explicitly enforces the consistency of semantic relation among different samples under perturbations, encouraging the model to explore extra semantic information from unlabeled data. We have conducted extensive experiments to evaluate our method on two public benchmark medical image classification datasets, i.e.,skin lesion diagnosis with ISIC 2018 challenge and thorax disease classification with ChestX-ray14. Our method outperforms many state-of-the-art semi-supervised learning methods on both single-label and multi-label image classification scenarios.

Xi Wang, Hao Chen, Luyang Luo et al.

Optical Coherence Tomography (OCT) imaging plays an important role in glaucoma diagnosis in clinical practice. Early detection and timely treatment can prevent glaucoma patients from permanent vision loss. However, only a dearth of automated methods has been developed based on OCT images for glaucoma study. In this paper, we present a novel framework to effectively classify glaucoma OCT images from normal ones. A semi-supervised learning strategy with smoothness assumption is applied for surrogate assignment of missing function regression labels. Besides, the proposed multi-task learning network is capable of exploring the structure and function relationship from the OCT image and visual field measurement simultaneously, which contributes to classification performance boosting. Essentially, we are the first to unify the structure analysis and function regression for glaucoma screening. It is also worth noting that we build the largest glaucoma OCT image dataset involving 4877 volumes to develop and evaluate the proposed method. Extensive experiments demonstrate that our framework outperforms the baseline methods and two glaucoma experts by a large margin, achieving 93.2%, 93.2% and 97.8% on accuracy, F1 score and AUC, respectively.

Luyang Luo, Hao Chen, Xi Wang et al.

Accurate and automatic analysis of breast MRI plays an important role in early diagnosis and successful treatment planning for breast cancer. Due to the heterogeneity nature, accurate diagnosis of tumors remains a challenging task. In this paper, we propose to identify breast tumor in MRI by Cosine Margin Sigmoid Loss (CMSL) with deep learning (DL) and localize possible cancer lesion by COrrelation Attention Map (COAM) based on the learned features. The CMSL embeds tumor features onto a hypersphere and imposes a decision margin through cosine constraints. In this way, the DL model could learn more separable inter-class features and more compact intra-class features in the angular space. Furthermore, we utilize the correlations among feature vectors to generate attention maps that could accurately localize cancer candidates with only image-level label. We build the largest breast cancer dataset involving 10,290 DCE-MRI scan volumes for developing and evaluating the proposed methods. The model driven by CMSL achieved classification accuracy of 0.855 and AUC of 0.902 on the testing set, with sensitivity and specificity of 0.857 and 0.852, respectively, outperforming other competitive methods overall. In addition, the proposed COAM accomplished more accurate localization of the cancer center compared with other state-of-the-art weakly supervised localization method.