Xiangde Luo

Guotai Wang, Xiangde Luo, Ran Gu et al.

Background and Objective: Open-source deep learning toolkits are one of the driving forces for developing medical image segmentation models. Existing toolkits mainly focus on fully supervised segmentation and require full and accurate pixel-level annotations that are time-consuming and difficult to acquire for segmentation tasks, which makes learning from imperfect labels highly desired for reducing the annotation cost. We aim to develop a new deep learning toolkit to support annotation-efficient learning for medical image segmentation. Methods: Our proposed toolkit named PyMIC is a modular deep learning library for medical image segmentation tasks. In addition to basic components that support development of high-performance models for fully supervised segmentation, it contains several advanced components tailored for learning from imperfect annotations, such as loading annotated and unannounced images, loss functions for unannotated, partially or inaccurately annotated images, and training procedures for co-learning between multiple networks, etc. PyMIC supports development of semi-supervised, weakly supervised and noise-robust learning methods for medical image segmentation. Results: We present several illustrative medical image segmentation tasks based on PyMIC: (1) Achieving competitive performance on fully supervised learning; (2) Semi-supervised cardiac structure segmentation with only 10% training images annotated; (3) Weakly supervised segmentation using scribble annotations; and (4) Learning from noisy labels for chest radiograph segmentation. Conclusions: The PyMIC toolkit is easy to use and facilitates efficient development of medical image segmentation models with imperfect annotations. It is modular and flexible, which enables researchers to develop high-performance models with low annotation cost. The source code is available at: https://github.com/HiLab-git/PyMIC.

Guotai Wang, Jianghao Wu, Xiangde Luo et al.

Pretraining with large-scale 3D volumes has a potential for improving the segmentation performance on a target medical image dataset where the training images and annotations are limited. Due to the high cost of acquiring pixel-level segmentation annotations on the large-scale pretraining dataset, pretraining with unannotated images is highly desirable. In this work, we propose a novel self-supervised learning strategy named Volume Fusion (VF) for pretraining 3D segmentation models. It fuses several random patches from a foreground sub-volume to a background sub-volume based on a predefined set of discrete fusion coefficients, and forces the model to predict the fusion coefficient of each voxel, which is formulated as a self-supervised segmentation task without manual annotations. Additionally, we propose a novel network architecture based on parallel convolution and transformer blocks that is suitable to be transferred to different downstream segmentation tasks with various scales of organs and lesions. The proposed model was pretrained with 110k unannotated 3D CT volumes, and experiments with different downstream segmentation targets including head and neck organs, thoracic/abdominal organs showed that our pretrained model largely outperformed training from scratch and several state-of-the-art self-supervised training methods and segmentation models. The code and pretrained model are available at https://github.com/openmedlab/MIS-FM.

Zihao Luo, Xiangde Luo, Zijun Gao et al.

Deep learning models have exhibited remarkable efficacy in accurately delineating the prostate for diagnosis and treatment of prostate diseases, but challenges persist in achieving robust generalization across different medical centers. Source-free Domain Adaptation (SFDA) is a promising technique to adapt deep segmentation models to address privacy and security concerns while reducing domain shifts between source and target domains. However, recent literature indicates that the performance of SFDA remains far from satisfactory due to unpredictable domain gaps. Annotating a few target domain samples is acceptable, as it can lead to significant performance improvement with a low annotation cost. Nevertheless, due to extremely limited annotation budgets, careful consideration is needed in selecting samples for annotation. Inspired by this, our goal is to develop Active Source-free Domain Adaptation (ASFDA) for medical image segmentation. Specifically, we propose a novel Uncertainty-guided Tiered Self-training (UGTST) framework, consisting of efficient active sample selection via entropy-based primary local peak filtering to aggregate global uncertainty and diversity-aware redundancy filter, coupled with a tiered self-learning strategy, achieves stable domain adaptation. Experimental results on cross-center prostate MRI segmentation datasets revealed that our method yielded marked advancements, with a mere 5% annotation, exhibiting an average Dice score enhancement of 9.78% and 7.58% in two target domains compared with state-of-the-art methods, on par with fully supervised learning. Code is available at:https://github.com/HiLab-git/UGTST

Hongqiu Wang, Jian Chen, Shichen Zhang et al.

Nasopharyngeal carcinoma (NPC) is a prevalent and clinically significant malignancy that predominantly impacts the head and neck area. Precise delineation of the Gross Tumor Volume (GTV) plays a pivotal role in ensuring effective radiotherapy for NPC. Despite recent methods that have achieved promising results on GTV segmentation, they are still limited by lacking carefully-annotated data and hard-to-access data from multiple hospitals in clinical practice. Although some unsupervised domain adaptation (UDA) has been proposed to alleviate this problem, unconditionally mapping the distribution distorts the underlying structural information, leading to inferior performance. To address this challenge, we devise a novel Sourece-Free Active Domain Adaptation (SFADA) framework to facilitate domain adaptation for the GTV segmentation task. Specifically, we design a dual reference strategy to select domain-invariant and domain-specific representative samples from a specific target domain for annotation and model fine-tuning without relying on source-domain data. Our approach not only ensures data privacy but also reduces the workload for oncologists as it just requires annotating a few representative samples from the target domain and does not need to access the source data. We collect a large-scale clinical dataset comprising 1057 NPC patients from five hospitals to validate our approach. Experimental results show that our method outperforms the UDA methods and achieves comparable results to the fully supervised upper bound, even with few annotations, highlighting the significant medical utility of our approach. In addition, there is no public dataset about multi-center NPC segmentation, we will release code and dataset for future research.

Zihan Li, Yuan Zheng, Xiangde Luo et al. · uw

Medical image segmentation plays a critical role in clinical decision-making, treatment planning, and disease monitoring. However, accurate segmentation of medical images is challenging due to several factors, such as the lack of high-quality annotation, imaging noise, and anatomical differences across patients. In addition, there is still a considerable gap in performance between the existing label-efficient methods and fully-supervised methods. To address the above challenges, we propose ScribbleVC, a novel framework for scribble-supervised medical image segmentation that leverages vision and class embeddings via the multimodal information enhancement mechanism. In addition, ScribbleVC uniformly utilizes the CNN features and Transformer features to achieve better visual feature extraction. The proposed method combines a scribble-based approach with a segmentation network and a class-embedding module to produce accurate segmentation masks. We evaluate ScribbleVC on three benchmark datasets and compare it with state-of-the-art methods. The experimental results demonstrate that our method outperforms existing approaches in terms of accuracy, robustness, and efficiency. The datasets and code are released on GitHub.

Jieneng Chen, Jieru Mei, Xianhang Li et al.

Medical image segmentation plays a crucial role in advancing healthcare systems for disease diagnosis and treatment planning. The u-shaped architecture, popularly known as U-Net, has proven highly successful for various medical image segmentation tasks. However, U-Net's convolution-based operations inherently limit its ability to model long-range dependencies effectively. To address these limitations, researchers have turned to Transformers, renowned for their global self-attention mechanisms, as alternative architectures. One popular network is our previous TransUNet, which leverages Transformers' self-attention to complement U-Net's localized information with the global context. In this paper, we extend the 2D TransUNet architecture to a 3D network by building upon the state-of-the-art nnU-Net architecture, and fully exploring Transformers' potential in both the encoder and decoder design. We introduce two key components: 1) A Transformer encoder that tokenizes image patches from a convolution neural network (CNN) feature map, enabling the extraction of global contexts, and 2) A Transformer decoder that adaptively refines candidate regions by utilizing cross-attention between candidate proposals and U-Net features. Our investigations reveal that different medical tasks benefit from distinct architectural designs. The Transformer encoder excels in multi-organ segmentation, where the relationship among organs is crucial. On the other hand, the Transformer decoder proves more beneficial for dealing with small and challenging segmented targets such as tumor segmentation. Extensive experiments showcase the significant potential of integrating a Transformer-based encoder and decoder into the u-shaped medical image segmentation architecture. TransUNet outperforms competitors in various medical applications.

Litingyu Wang, Yijie Qu, Xiangde Luo et al.

Assessing the presence of potentially malignant lymph nodes aids in estimating cancer progression, and identifying surrounding benign lymph nodes can assist in determining potential metastatic pathways for cancer. For quantitative analysis, automatic segmentation of lymph nodes is crucial. However, due to the labor-intensive and time-consuming manual annotation process required for a large number of lymph nodes, it is more practical to annotate only a subset of the lymph node instances to reduce annotation costs. In this study, we propose a pre-trained Dual-Branch network with Dynamically Mixed Pseudo label (DBDMP) to learn from partial instance annotations for lymph nodes segmentation. To obtain reliable pseudo labels for lymph nodes that are not annotated, we employ a dual-decoder network to generate different outputs that are then dynamically mixed. We integrate the original weak partial annotations with the mixed pseudo labels to supervise the network. To further leverage the extensive amount of unannotated voxels, we apply a self-supervised pre-training strategy to enhance the model's feature extraction capability. Experiments on the mediastinal Lymph Node Quantification (LNQ) dataset demonstrate that our method, compared to directly learning from partial instance annotations, significantly improves the Dice Similarity Coefficient (DSC) from 11.04% to 54.10% and reduces the Average Symmetric Surface Distance (ASSD) from 20.83 $mm$ to 8.72 $mm$. The code is available at https://github.com/WltyBY/LNQ2023_training_code.git

Xiangde Luo, Minhao Hu, Wenjun Liao et al.

Medical image segmentation plays an irreplaceable role in computer-assisted diagnosis, treatment planning, and following-up. Collecting and annotating a large-scale dataset is crucial to training a powerful segmentation model, but producing high-quality segmentation masks is an expensive and time-consuming procedure. Recently, weakly-supervised learning that uses sparse annotations (points, scribbles, bounding boxes) for network training has achieved encouraging performance and shown the potential for annotation cost reduction. However, due to the limited supervision signal of sparse annotations, it is still challenging to employ them for networks training directly. In this work, we propose a simple yet efficient scribble-supervised image segmentation method and apply it to cardiac MRI segmentation. Specifically, we employ a dual-branch network with one encoder and two slightly different decoders for image segmentation and dynamically mix the two decoders' predictions to generate pseudo labels for auxiliary supervision. By combining the scribble supervision and auxiliary pseudo labels supervision, the dual-branch network can efficiently learn from scribble annotations end-to-end. Experiments on the public ACDC dataset show that our method performs better than current scribble-supervised segmentation methods and also outperforms several semi-supervised segmentation methods.

Jianghao Wu, Xiangde Luo, Yubo Zhou et al.

Test-Time Adaptation (TTA) offers a practical solution for deploying image segmentation models under domain shift without accessing source data or retraining. Among existing TTA strategies, pseudo-label-based methods have shown promising performance. However, they often rely on perturbation-ensemble heuristics (e.g., dropout sampling, test-time augmentation, Gaussian noise), which lack distributional grounding and yield unstable training signals. This can trigger error accumulation and catastrophic forgetting during adaptation. To address this, we propose \textbf{A3-TTA}, a TTA framework that constructs reliable pseudo-labels through anchor-guided supervision. Specifically, we identify well-predicted target domain images using a class compact density metric, under the assumption that confident predictions imply distributional proximity to the source domain. These anchors serve as stable references to guide pseudo-label generation, which is further regularized via semantic consistency and boundary-aware entropy minimization. Additionally, we introduce a self-adaptive exponential moving average strategy to mitigate label noise and stabilize model update during adaptation. Evaluated on both multi-domain medical images (heart structure and prostate segmentation) and natural images, A3-TTA significantly improves average Dice scores by 10.40 to 17.68 percentage points compared to the source model, outperforming several state-of-the-art TTA methods under different segmentation model architectures. A3-TTA also excels in continual TTA, maintaining high performance across sequential target domains with strong anti-forgetting ability. The code will be made publicly available at https://github.com/HiLab-git/A3-TTA.

Shuwei Zhai, Guotai Wang, Xiangde Luo et al.

The success of Convolutional Neural Networks (CNNs) in 3D medical image segmentation relies on massive fully annotated 3D volumes for training that are time-consuming and labor-intensive to acquire. In this paper, we propose to annotate a segmentation target with only seven points in 3D medical images, and design a two-stage weakly supervised learning framework PA-Seg. In the first stage, we employ geodesic distance transform to expand the seed points to provide more supervision signal. To further deal with unannotated image regions during training, we propose two contextual regularization strategies, i.e., multi-view Conditional Random Field (mCRF) loss and Variance Minimization (VM) loss, where the first one encourages pixels with similar features to have consistent labels, and the second one minimizes the intensity variance for the segmented foreground and background, respectively. In the second stage, we use predictions obtained by the model pre-trained in the first stage as pseudo labels. To overcome noises in the pseudo labels, we introduce a Self and Cross Monitoring (SCM) strategy, which combines self-training with Cross Knowledge Distillation (CKD) between a primary model and an auxiliary model that learn from soft labels generated by each other. Experiments on public datasets for Vestibular Schwannoma (VS) segmentation and Brain Tumor Segmentation (BraTS) demonstrated that our model trained in the first stage outperformed existing state-of-the-art weakly supervised approaches by a large margin, and after using SCM for additional training, the model's performance was close to its fully supervised counterpart on the BraTS dataset.

Meng Han, Xiangde Luo, Wenjun Liao et al.

Multi-organ segmentation in abdominal Computed Tomography (CT) images is of great importance for diagnosis of abdominal lesions and subsequent treatment planning. Though deep learning based methods have attained high performance, they rely heavily on large-scale pixel-level annotations that are time-consuming and labor-intensive to obtain. Due to its low dependency on annotation, weakly supervised segmentation has attracted great attention. However, there is still a large performance gap between current weakly-supervised methods and fully supervised learning, leaving room for exploration. In this work, we propose a novel 3D framework with two consistency constraints for scribble-supervised multiple abdominal organ segmentation from CT. Specifically, we employ a Triple-branch multi-Dilated network (TDNet) with one encoder and three decoders using different dilation rates to capture features from different receptive fields that are complementary to each other to generate high-quality soft pseudo labels. For more stable unsupervised learning, we use voxel-wise uncertainty to rectify the soft pseudo labels and then supervise the outputs of each decoder. To further regularize the network, class relationship information is exploited by encouraging the generated class affinity matrices to be consistent across different decoders under multi-view projection. Experiments on the public WORD dataset show that our method outperforms five existing scribble-supervised methods.

Yunxiang Li, Ruilong Dan, Shuai Wang et al.

Skull stripping is a crucial prerequisite step in the analysis of brain magnetic resonance images (MRI). Although many excellent works or tools have been proposed, they suffer from low generalization capability. For instance, the model trained on a dataset with specific imaging parameters cannot be well applied to other datasets with different imaging parameters. Especially, for the lifespan datasets, the model trained on an adult dataset is not applicable to an infant dataset due to the large domain difference. To address this issue, numerous methods have been proposed, where domain adaptation based on feature alignment is the most common. Unfortunately, this method has some inherent shortcomings, which need to be retrained for each new domain and requires concurrent access to the input images of both domains. In this paper, we design a plug-and-play shape refinement (PSR) framework for multi-site and lifespan skull stripping. To deal with the domain shift between multi-site lifespan datasets, we take advantage of the brain shape prior, which is invariant to imaging parameters and ages. Experiments demonstrate that our framework can outperform the state-of-the-art methods on multi-site lifespan datasets.

Jinxi Xiang, Mingjie Li, Siyu Hou et al.

Accurate diagnosis and treatment of complex diseases require integrating histological, molecular, and clinical data, yet in practice these modalities are often incomplete owing to tissue scarcity, assay cost, and workflow constraints. Existing computational approaches attempt to impute missing modalities from available data but rely on task-specific models trained on narrow, single source-target pairs, limiting their generalizability. Here we introduce MuPD (Multimodal Pathology Diffusion), a generative foundation model that embeds hematoxylin and eosin (H&E)-stained histology, molecular RNA profiles, and clinical text into a shared latent space through a diffusion transformer with decoupled cross-modal attention. Pretrained on 100 million histology image patches, 1.6 million text-histology pairs, and 10.8 million RNA-histology pairs spanning 34 human organs, MuPD supports diverse cross-modal synthesis tasks with minimal or no task-specific fine-tuning. For text-conditioned and image-to-image generation, MuPD synthesizes histologically faithful tissue architectures, reducing Fréchet inception distance (FID) scores by 50% relative to domain-specific models and improving few-shot classification accuracy by up to 47% through synthetic data augmentation. For RNA-conditioned histology generation, MuPD reduces FID by 23% compared with the next-best method while preserving cell-type distributions across five cancer types. As a virtual stainer, MuPD translates H&E images to immunohistochemistry and multiplex immunofluorescence, improving average marker correlation by 37% over existing approaches. These results demonstrate that a single, unified generative model pretrained across heterogeneous pathology modalities can substantially outperform specialized alternatives, providing a scalable computational framework for multimodal histopathology.

Jinxi Xiang, Siyu Hou, Yuchen Li et al.

Spatial transcriptomics (ST) enables gene expression mapping within anatomical context but remains costly and low-throughput. Hematoxylin and eosin (H\&E) staining offers rich morphology yet lacks molecular resolution. We present \textbf{\ours} (\textbf{S}patial \textbf{T}ranscriptomics and hist\textbf{O}logy \textbf{R}epresentation \textbf{M}odel), a foundation model trained on 1.2 million spatially resolved transcriptomic profiles with matched histology across 18 organs. Using a hierarchical architecture integrating morphological features, gene expression, and spatial context, STORM bridges imaging and omics through robust molecular--morphological representations. STORM enhances spatial domain discovery, producing biologically coherent tissue maps, and outperforms existing methods in predicting spatial gene expression from H\&E images across 11 tumor types. The model is platform-agnostic, performing consistently across Visium, Xenium, Visium HD, and CosMx. Applied to 23 independent cohorts comprising 7,245 patients, STORM significantly improves immunotherapy response prediction and prognostication over established biomarkers, providing a scalable framework for spatially informed discovery and clinical precision medicine.

Yicheng Wu, Xiangde Luo, Zhe Xu et al.

Annotation ambiguity due to inherent data uncertainties such as blurred boundaries in medical scans and different observer expertise and preferences has become a major obstacle for training deep-learning based medical image segmentation models. To address it, the common practice is to gather multiple annotations from different experts, leading to the setting of multi-rater medical image segmentation. Existing works aim to either merge different annotations into the "groundtruth" that is often unattainable in numerous medical contexts, or generate diverse results, or produce personalized results corresponding to individual expert raters. Here, we bring up a more ambitious goal for multi-rater medical image segmentation, i.e., obtaining both diversified and personalized results. Specifically, we propose a two-stage framework named D-Persona (first Diversification and then Personalization). In Stage I, we exploit multiple given annotations to train a Probabilistic U-Net model, with a bound-constrained loss to improve the prediction diversity. In this way, a common latent space is constructed in Stage I, where different latent codes denote diversified expert opinions. Then, in Stage II, we design multiple attention-based projection heads to adaptively query the corresponding expert prompts from the shared latent space, and then perform the personalized medical image segmentation. We evaluated the proposed model on our in-house Nasopharyngeal Carcinoma dataset and the public lung nodule dataset (i.e., LIDC-IDRI). Extensive experiments demonstrated our D-Persona can provide diversified and personalized results at the same time, achieving new SOTA performance for multi-rater medical image segmentation. Our code will be released at https://github.com/ycwu1997/D-Persona.

Xingyue Zhao, Peiqi Li, Xiangde Luo et al.

Automated nodule segmentation is essential for computer-assisted diagnosis in ultrasound images. Nevertheless, most existing methods depend on precise pixel-level annotations by medical professionals, a process that is both costly and labor-intensive. Recently, segmentation foundation models like SAM have shown impressive generalizability on natural images, suggesting their potential as pseudo-labelers. However, accurate prompts remain crucial for their success in medical images. In this work, we devise a novel weakly supervised framework that effectively utilizes the segmentation foundation model to generate pseudo-labels from aspect ration annotations for automatic nodule segmentation. Specifically, we develop three types of bounding box prompts based on scalable shape priors, followed by an adaptive pseudo-label selection module to fully exploit the prediction capabilities of the foundation model for nodules. We also present a SAM-driven uncertainty-aware cross-teaching strategy. This approach integrates SAM-based uncertainty estimation and label-space perturbations into cross-teaching to mitigate the impact of pseudo-label inaccuracies on model training. Extensive experiments on two clinically collected ultrasound datasets demonstrate the superior performance of our proposed method.

Ziqi Yang, Zhongyu Li, Chen Liu et al.

Convolutional neural networks excel in histopathological image classification, yet their pixel-level focus hampers explainability. Conversely, emerging graph convolutional networks spotlight cell-level features and medical implications. However, limited by their shallowness and suboptimal use of high-dimensional pixel data, GCNs underperform in multi-class histopathological image classification. To make full use of pixel-level and cell-level features dynamically, we propose an asymmetric co-training framework combining a deep graph convolutional network and a convolutional neural network for multi-class histopathological image classification. To improve the explainability of the entire framework by embedding morphological and topological distribution of cells, we build a 14-layer deep graph convolutional network to handle cell graph data. For the further utilization and dynamic interactions between pixel-level and cell-level information, we also design a co-training strategy to integrate the two asymmetric branches. Notably, we collect a private clinically acquired dataset termed LUAD7C, including seven subtypes of lung adenocarcinoma, which is rare and more challenging. We evaluated our approach on the private LUAD7C and public colorectal cancer datasets, showcasing its superior performance, explainability, and generalizability in multi-class histopathological image classification.

Han Zhang, Xiangde Luo, Yong Chen et al.

Annotation variability remains a substantial challenge in medical image segmentation, stemming from ambiguous imaging boundaries and diverse clinical expertise. Traditional deep learning methods producing single deterministic segmentation predictions often fail to capture these annotator biases. Although recent studies have explored multi-rater segmentation, existing methods typically focus on a single perspective -- either generating a probabilistic ``gold standard'' consensus or preserving expert-specific preferences -- thus struggling to provide a more omni view. In this study, we propose DiffOSeg, a two-stage diffusion-based framework, which aims to simultaneously achieve both consensus-driven (combining all experts' opinions) and preference-driven (reflecting experts' individual assessments) segmentation. Stage I establishes population consensus through a probabilistic consensus strategy, while Stage II captures expert-specific preference via adaptive prompts. Demonstrated on two public datasets (LIDC-IDRI and NPC-170), our model outperforms existing state-of-the-art methods across all evaluated metrics. Source code is available at https://github.com/string-ellipses/DiffOSeg .

Xiangde Luo, Zihan Li, Shaoting Zhang et al.

Deep learning has enabled great strides in abdominal multi-organ segmentation, even surpassing junior oncologists on common cases or organs. However, robustness on corner cases and complex organs remains a challenging open problem for clinical adoption. To investigate model robustness, we collected and annotated the RAOS dataset comprising 413 CT scans ($\sim$80k 2D images, $\sim$8k 3D organ annotations) from 413 patients each with 17 (female) or 19 (male) labelled organs, manually delineated by oncologists. We grouped scans based on clinical information into 1) diagnosis/radiotherapy (317 volumes), 2) partial excision without the whole organ missing (22 volumes), and 3) excision with the whole organ missing (74 volumes). RAOS provides a potential benchmark for evaluating model robustness including organ hallucination. It also includes some organs that can be very hard to access on public datasets like the rectum, colon, intestine, prostate and seminal vesicles. We benchmarked several state-of-the-art methods in these three clinical groups to evaluate performance and robustness. We also assessed cross-generalization between RAOS and three public datasets. This dataset and comprehensive analysis establish a potential baseline for future robustness research: \url{https://github.com/Luoxd1996/RAOS}.

Hongqiu Wang, Xiangde Luo, Wu Chen et al.

Accurate vessel segmentation in Ultra-Wide-Field Scanning Laser Ophthalmoscopy (UWF-SLO) images is crucial for diagnosing retinal diseases. Although recent techniques have shown encouraging outcomes in vessel segmentation, models trained on one medical dataset often underperform on others due to domain shifts. Meanwhile, manually labeling high-resolution UWF-SLO images is an extremely challenging, time-consuming and expensive task. In response, this study introduces a pioneering framework that leverages a patch-based active domain adaptation approach. By actively recommending a few valuable image patches by the devised Cascade Uncertainty-Predominance (CUP) selection strategy for labeling and model-finetuning, our method significantly improves the accuracy of UWF-SLO vessel segmentation across diverse medical centers. In addition, we annotate and construct the first Multi-center UWF-SLO Vessel Segmentation (MU-VS) dataset to promote this topic research, comprising data from multiple institutions. This dataset serves as a valuable resource for cross-center evaluation, verifying the effectiveness and robustness of our approach. Experimental results demonstrate that our approach surpasses existing domain adaptation and active learning methods, considerably reducing the gap between the Upper and Lower bounds with minimal annotations, highlighting our method's practical clinical value. We will release our dataset and code to facilitate relevant research: https://github.com/whq-xxh/SFADA-UWF-SLO.

Zihao Luo, Zijun Gao, Wenjun Liao et al.

Accurate lymph node (LN) segmentation is critical in radiotherapy treatment and prognosis analysis, but is limited by the need for large annotated datasets. While deep learning-based segmentation foundation models show potential in developing high-performing models with fewer samples, their medical adaptation faces LN domain-specific prior deficiencies and inefficient few-shot fine-tuning for complex clinical practices, highlighting the necessity of an LN segmentation foundation model. In this work, we annotated 36,106 visible LNs from 3,346 publicly available head-and-neck CT scans to establish a robust LN segmentation model (nnUNetv2). Building on this, we propose Dynamic Gradient Sparsification Training (DGST), a few-shot fine-tuning approach that preserves foundational knowledge while dynamically updating the most critical parameters of the LN segmentation model with few annotations. We validate it on two publicly available LN segmentation datasets: SegRap2023 and LNQ2023. The results show that DGST outperforms existing few-shot fine-tuning methods, achieving satisfactory performance with limited labeled data. We release the dataset, models and all implementations to facilitate relevant research: https://github.com/Zihaoluoh/LN-Seg-FM.

Tao Song, Yicheng Wu, Minhao Hu et al.

Multimodal MR image synthesis aims to generate missing modality images by effectively fusing and mapping from a subset of available MRI modalities. Most existing methods adopt an image-to-image translation paradigm, treating multiple modalities as input channels. However, these approaches often yield sub-optimal results due to the inherent difficulty in achieving precise feature- or semantic-level alignment across modalities. To address these challenges, we propose an Adaptive Group-wise Interaction Network (AGI-Net) that explicitly models both inter-modality and intra-modality relationships for multimodal MR image synthesis. Specifically, feature channels are first partitioned into predefined groups, after which an adaptive rolling mechanism is applied to conventional convolutional kernels to better capture feature and semantic correspondences between different modalities. In parallel, a cross-group attention module is introduced to enable effective feature fusion across groups, thereby enhancing the network's representational capacity. We validate the proposed AGI-Net on the publicly available IXI and BraTS2023 datasets. Experimental results demonstrate that AGI-Net achieves state-of-the-art performance in multimodal MR image synthesis tasks, confirming the effectiveness of its modality-aware interaction design. We release the relevant code at: https://github.com/zunzhumu/Adaptive-Group-wise-Interaction-Network-for-Multimodal-MRI-Synthesis.git.

Xiangde Luo, Minhao Hu, Tao Song et al.

Recently, deep learning with Convolutional Neural Networks (CNNs) and Transformers has shown encouraging results in fully supervised medical image segmentation. However, it is still challenging for them to achieve good performance with limited annotations for training. In this work, we present a very simple yet efficient framework for semi-supervised medical image segmentation by introducing the cross teaching between CNN and Transformer. Specifically, we simplify the classical deep co-training from consistency regularization to cross teaching, where the prediction of a network is used as the pseudo label to supervise the other network directly end-to-end. Considering the difference in learning paradigm between CNN and Transformer, we introduce the Cross Teaching between CNN and Transformer rather than just using CNNs. Experiments on a public benchmark show that our method outperforms eight existing semi-supervised learning methods just with a simpler framework. Notably, this work may be the first attempt to combine CNN and transformer for semi-supervised medical image segmentation and achieve promising results on a public benchmark. The code will be released at: https://github.com/HiLab-git/SSL4MIS.

Shaohua Li, Xiuchao Sui, Jie Fu et al.

Deep neural networks (DNNs) trained on one set of medical images often experience severe performance drop on unseen test images, due to various domain discrepancy between the training images (source domain) and the test images (target domain), which raises a domain adaptation issue. In clinical settings, it is difficult to collect enough annotated target domain data in a short period. Few-shot domain adaptation, i.e., adapting a trained model with a handful of annotations, is highly practical and useful in this case. In this paper, we propose a Polymorphic Transformer (Polyformer), which can be incorporated into any DNN backbones for few-shot domain adaptation. Specifically, after the polyformer layer is inserted into a model trained on the source domain, it extracts a set of prototype embeddings, which can be viewed as a "basis" of the source-domain features. On the target domain, the polyformer layer adapts by only updating a projection layer which controls the interactions between image features and the prototype embeddings. All other model weights (except BatchNorm parameters) are frozen during adaptation. Thus, the chance of overfitting the annotations is greatly reduced, and the model can perform robustly on the target domain after being trained on a few annotated images. We demonstrate the effectiveness of Polyformer on two medical segmentation tasks (i.e., optic disc/cup segmentation, and polyp segmentation). The source code of Polyformer is released at https://github.com/askerlee/segtran.

Shaohua Li, Xiuchao Sui, Xiangde Luo et al.

Medical image segmentation is important for computer-aided diagnosis. Good segmentation demands the model to see the big picture and fine details simultaneously, i.e., to learn image features that incorporate large context while keep high spatial resolutions. To approach this goal, the most widely used methods -- U-Net and variants, extract and fuse multi-scale features. However, the fused features still have small "effective receptive fields" with a focus on local image cues, limiting their performance. In this work, we propose Segtran, an alternative segmentation framework based on transformers, which have unlimited "effective receptive fields" even at high feature resolutions. The core of Segtran is a novel Squeeze-and-Expansion transformer: a squeezed attention block regularizes the self attention of transformers, and an expansion block learns diversified representations. Additionally, we propose a new positional encoding scheme for transformers, imposing a continuity inductive bias for images. Experiments were performed on 2D and 3D medical image segmentation tasks: optic disc/cup segmentation in fundus images (REFUGE'20 challenge), polyp segmentation in colonoscopy images, and brain tumor segmentation in MRI scans (BraTS'19 challenge). Compared with representative existing methods, Segtran consistently achieved the highest segmentation accuracy, and exhibited good cross-domain generalization capabilities. The source code of Segtran is released at https://github.com/askerlee/segtran.

Jieneng Chen, Yongyi Lu, Qihang Yu et al.

Medical image segmentation is an essential prerequisite for developing healthcare systems, especially for disease diagnosis and treatment planning. On various medical image segmentation tasks, the u-shaped architecture, also known as U-Net, has become the de-facto standard and achieved tremendous success. However, due to the intrinsic locality of convolution operations, U-Net generally demonstrates limitations in explicitly modeling long-range dependency. Transformers, designed for sequence-to-sequence prediction, have emerged as alternative architectures with innate global self-attention mechanisms, but can result in limited localization abilities due to insufficient low-level details. In this paper, we propose TransUNet, which merits both Transformers and U-Net, as a strong alternative for medical image segmentation. On one hand, the Transformer encodes tokenized image patches from a convolution neural network (CNN) feature map as the input sequence for extracting global contexts. On the other hand, the decoder upsamples the encoded features which are then combined with the high-resolution CNN feature maps to enable precise localization. We argue that Transformers can serve as strong encoders for medical image segmentation tasks, with the combination of U-Net to enhance finer details by recovering localized spatial information. TransUNet achieves superior performances to various competing methods on different medical applications including multi-organ segmentation and cardiac segmentation. Code and models are available at https://github.com/Beckschen/TransUNet.

Xu Chen, Xiangde Luo, Yitian Zhao et al.

Image segmentation is a fundamental topic in image processing and has been studied for many decades. Deep learning-based supervised segmentation models have achieved state-of-the-art performance but most of them are limited by using pixel-wise loss functions for training without geometrical constraints. Inspired by Euler's Elastica model and recent active contour models introduced into the field of deep learning, we propose a novel active contour with elastica (ACE) loss function incorporating Elastica (curvature and length) and region information as geometrically-natural constraints for the image segmentation tasks. We introduce the mean curvature i.e. the average of all principal curvatures, as a more effective image prior to representing curvature in our ACE loss function. Furthermore, based on the definition of the mean curvature, we propose a fast solution to approximate the ACE loss in three-dimensional (3D) by using Laplace operators for 3D image segmentation. We evaluate our ACE loss function on four 2D and 3D natural and biomedical image datasets. Our results show that the proposed loss function outperforms other mainstream loss functions on different segmentation networks. Our source code is available at https://github.com/HiLab-git/ACELoss.

Xiangde Luo, Jieneng Chen, Tao Song et al.

Deep learning-based semi-supervised learning (SSL) algorithms have led to promising results in medical images segmentation and can alleviate doctors' expensive annotations by leveraging unlabeled data. However, most of the existing SSL algorithms in literature tend to regularize the model training by perturbing networks and/or data. Observing that multi/dual-task learning attends to various levels of information which have inherent prediction perturbation, we ask the question in this work: can we explicitly build task-level regularization rather than implicitly constructing networks- and/or data-level perturbation-and-transformation for SSL? To answer this question, we propose a novel dual-task-consistency semi-supervised framework for the first time. Concretely, we use a dual-task deep network that jointly predicts a pixel-wise segmentation map and a geometry-aware level set representation of the target. The level set representation is converted to an approximated segmentation map through a differentiable task transform layer. Simultaneously, we introduce a dual-task consistency regularization between the level set-derived segmentation maps and directly predicted segmentation maps for both labeled and unlabeled data. Extensive experiments on two public datasets show that our method can largely improve the performance by incorporating the unlabeled data. Meanwhile, our framework outperforms the state-of-the-art semi-supervised medical image segmentation methods. Code is available at: https://github.com/Luoxd1996/DTC

Xiangde Luo, Jia Fu, Yunxin Zhong et al.

Radiation therapy is a primary and effective NasoPharyngeal Carcinoma (NPC) treatment strategy. The precise delineation of Gross Tumor Volumes (GTVs) and Organs-At-Risk (OARs) is crucial in radiation treatment, directly impacting patient prognosis. Previously, the delineation of GTVs and OARs was performed by experienced radiation oncologists. Recently, deep learning has achieved promising results in many medical image segmentation tasks. However, for NPC OARs and GTVs segmentation, few public datasets are available for model development and evaluation. To alleviate this problem, the SegRap2023 challenge was organized in conjunction with MICCAI2023 and presented a large-scale benchmark for OAR and GTV segmentation with 400 Computed Tomography (CT) scans from 200 NPC patients, each with a pair of pre-aligned non-contrast and contrast-enhanced CT scans. The challenge's goal was to segment 45 OARs and 2 GTVs from the paired CT scans. In this paper, we detail the challenge and analyze the solutions of all participants. The average Dice similarity coefficient scores for all submissions ranged from 76.68\% to 86.70\%, and 70.42\% to 73.44\% for OARs and GTVs, respectively. We conclude that the segmentation of large-size OARs is well-addressed, and more efforts are needed for GTVs and small-size or thin-structure OARs. The benchmark will remain publicly available here: https://segrap2023.grand-challenge.org

Xingyue Zhao, Zhongyu Li, Xiangde Luo et al.

Recent advances in deep learning have greatly facilitated the automated segmentation of ultrasound images, which is essential for nodule morphological analysis. Nevertheless, most existing methods depend on extensive and precise annotations by domain experts, which are labor-intensive and time-consuming. In this study, we suggest using simple aspect ratio annotations directly from ultrasound clinical diagnoses for automated nodule segmentation. Especially, an asymmetric learning framework is developed by extending the aspect ratio annotations with two types of pseudo labels, i.e., conservative labels and radical labels, to train two asymmetric segmentation networks simultaneously. Subsequently, a conservative-radical-balance strategy (CRBS) strategy is proposed to complementally combine radical and conservative labels. An inconsistency-aware dynamically mixed pseudo-labels supervision (IDMPS) module is introduced to address the challenges of over-segmentation and under-segmentation caused by the two types of labels. To further leverage the spatial prior knowledge provided by clinical annotations, we also present a novel loss function namely the clinical anatomy prior loss. Extensive experiments on two clinically collected ultrasound datasets (thyroid and breast) demonstrate the superior performance of our proposed method, which can achieve comparable and even better performance than fully supervised methods using ground truth annotations.

Xiangde Luo, Xiyue Wang, Feyisope Eweje et al.

Histopathology is essential for disease diagnosis and treatment decision-making. Recent advances in artificial intelligence (AI) have enabled the development of pathology foundation models that learn rich visual representations from large-scale whole-slide images (WSIs). However, existing models are often trained on disparate datasets using varying strategies, leading to inconsistent performance and limited generalizability. Here, we introduce ELF (Ensemble Learning of Foundation models), a novel framework that integrates five state-of-the-art pathology foundation models to generate unified slide-level representations. Trained on 53,699 WSIs spanning 20 anatomical sites, ELF leverages ensemble learning to capture complementary information from diverse models while maintaining high data efficiency. Unlike traditional tile-level models, ELF's slide-level architecture is particularly advantageous in clinical contexts where data are limited, such as therapeutic response prediction. We evaluated ELF across a wide range of clinical applications, including disease classification, biomarker detection, and response prediction to major anticancer therapies, cytotoxic chemotherapy, targeted therapy, and immunotherapy, across multiple cancer types. ELF consistently outperformed all constituent foundation models and existing slide-level models, demonstrating superior accuracy and robustness. Our results highlight the power of ensemble learning for pathology foundation models and suggest ELF as a scalable and generalizable solution for advancing AI-assisted precision oncology.

Tao Song, Yicheng Wu, Minhao Hu et al.

Accelerated MRI reconstruction plays a vital role in reducing scan time while preserving image quality. While most existing methods rely on complex-valued image-space or k-space data, these formats are often inaccessible in clinical practice due to proprietary reconstruction pipelines, leaving only magnitude images stored in DICOM files. To address this gap, we focus on the underexplored task of magnitude-image-based MRI reconstruction. Recent advancements in diffusion models, particularly denoising diffusion probabilistic models (DDPMs), have demonstrated strong capabilities in modeling image priors. However, their task-agnostic denoising nature limits performance in source-to-target image translation tasks, such as MRI reconstruction. In this work, we propose a novel Self-Consistent Nested Diffusion Bridge (SC-NDB) framework that models accelerated MRI reconstruction as a bi-directional image translation process between under-sampled and fully-sampled magnitude MRI images. SC-NDB introduces a nested diffusion architecture with a self-consistency constraint and reverse bridge diffusion pathways to improve intermediate prediction fidelity and better capture the explicit priors of source images. Furthermore, we incorporate a Contour Decomposition Embedding Module (CDEM) to inject structural and textural knowledge by leveraging Laplacian pyramids and directional filter banks. Extensive experiments on the fastMRI and IXI datasets demonstrate that our method achieves state-of-the-art performance compared to both magnitude-based and non-magnitude-based diffusion models, confirming the effectiveness and clinical relevance of SC-NDB.

Xiangde Luo, Jinxi Xiang, Yuanfeng Ji et al.

Computational pathology holds substantial promise for improving diagnosis and guiding treatment decisions. Recent pathology foundation models enable the extraction of rich patch-level representations from large-scale whole-slide images (WSIs), but current approaches for aggregating these features into slide-level predictions remain constrained by design limitations that hinder generalizability and reliability. Here, we developed nnMIL, a simple yet broadly applicable multiple-instance learning framework that connects patch-level foundation models to robust slide-level clinical inference. nnMIL introduces random sampling at both the patch and feature levels, enabling large-batch optimization, task-aware sampling strategies, and efficient and scalable training across datasets and model architectures. A lightweight aggregator performs sliding-window inference to generate ensemble slide-level predictions and supports principled uncertainty estimation. Across 40,000 WSIs encompassing 35 clinical tasks and four pathology foundation models, nnMIL consistently outperformed existing MIL methods for disease diagnosis, histologic subtyping, molecular biomarker detection, and pan- cancer prognosis prediction. It further demonstrated strong cross-model generalization, reliable uncertainty quantification, and robust survival stratification in multiple external cohorts. In conclusion, nnMIL offers a practical and generalizable solution for translating pathology foundation models into clinically meaningful predictions, advancing the development and deployment of reliable AI systems in real-world settings.

Yiwen Ye, Yicheng Wu, Xiangde Luo et al.

Foundation models have become a promising paradigm for advancing medical image analysis, particularly for segmentation tasks where downstream applications often emerge sequentially. Existing fine-tuning strategies, however, remain limited: parallel fine-tuning isolates tasks and fails to exploit shared knowledge, while multi-task fine-tuning requires simultaneous access to all datasets and struggles with incremental task integration. To address these challenges, we propose MedSeqFT, a sequential fine-tuning framework that progressively adapts pre-trained models to new tasks while refining their representational capacity. MedSeqFT introduces two core components: (1) Maximum Data Similarity (MDS) selection, which identifies downstream samples most representative of the original pre-training distribution to preserve general knowledge, and (2) Knowledge and Generalization Retention Fine-Tuning (K&G RFT), a LoRA-based knowledge distillation scheme that balances task-specific adaptation with the retention of pre-trained knowledge. Extensive experiments on two multi-task datasets covering ten 3D segmentation tasks demonstrate that MedSeqFT consistently outperforms state-of-the-art fine-tuning strategies, yielding substantial performance gains (e.g., an average Dice improvement of 3.0%). Furthermore, evaluations on two unseen tasks (COVID-19-20 and Kidney) verify that MedSeqFT enhances transferability, particularly for tumor segmentation. Visual analyses of loss landscapes and parameter variations further highlight the robustness of MedSeqFT. These results establish sequential fine-tuning as an effective, knowledge-retentive paradigm for adapting foundation models to evolving clinical tasks. Code will be released.

Yuanfeng Ji, Dan Lin, Xiyue Wang et al.

The scarcity of well-annotated diverse medical images is a major hurdle for developing reliable AI models in healthcare. Substantial technical advances have been made in generative foundation models for natural images. Here we develop `ChexGen', a generative vision-language foundation model that introduces a unified framework for text-, mask-, and bounding box-guided synthesis of chest radiographs. Built upon the latent diffusion transformer architecture, ChexGen was pretrained on the largest curated chest X-ray dataset to date, consisting of 960,000 radiograph-report pairs. ChexGen achieves accurate synthesis of radiographs through expert evaluations and quantitative metrics. We demonstrate the utility of ChexGen for training data augmentation and supervised pretraining, which led to performance improvements across disease classification, detection, and segmentation tasks using a small fraction of training data. Further, our model enables the creation of diverse patient cohorts that enhance model fairness by detecting and mitigating demographic biases. Our study supports the transformative role of generative foundation models in building more accurate, data-efficient, and equitable medical AI systems.

Xiangde Luo, Wenjun Liao, Jianghong Xiao et al.

Whole abdominal organ segmentation is important in diagnosing abdomen lesions, radiotherapy, and follow-up. However, oncologists' delineating all abdominal organs from 3D volumes is time-consuming and very expensive. Deep learning-based medical image segmentation has shown the potential to reduce manual delineation efforts, but it still requires a large-scale fine annotated dataset for training, and there is a lack of large-scale datasets covering the whole abdomen region with accurate and detailed annotations for the whole abdominal organ segmentation. In this work, we establish a new large-scale \textit{W}hole abdominal \textit{OR}gan \textit{D}ataset (\textit{WORD}) for algorithm research and clinical application development. This dataset contains 150 abdominal CT volumes (30495 slices). Each volume has 16 organs with fine pixel-level annotations and scribble-based sparse annotations, which may be the largest dataset with whole abdominal organ annotation. Several state-of-the-art segmentation methods are evaluated on this dataset. And we also invited three experienced oncologists to revise the model predictions to measure the gap between the deep learning method and oncologists. Afterwards, we investigate the inference-efficient learning on the WORD, as the high-resolution image requires large GPU memory and a long inference time in the test stage. We further evaluate the scribble-based annotation-efficient learning on this dataset, as the pixel-wise manual annotation is time-consuming and expensive. The work provided a new benchmark for the abdominal multi-organ segmentation task, and these experiments can serve as the baseline for future research and clinical application development.

Xiangde Luo, Guotai Wang, Tao Song et al.

Segmentation of organs or lesions from medical images plays an essential role in many clinical applications such as diagnosis and treatment planning. Though Convolutional Neural Networks (CNN) have achieved the state-of-the-art performance for automatic segmentation, they are often limited by the lack of clinically acceptable accuracy and robustness in complex cases. Therefore, interactive segmentation is a practical alternative to these methods. However, traditional interactive segmentation methods require a large amount of user interactions, and recently proposed CNN-based interactive segmentation methods are limited by poor performance on previously unseen objects. To solve these problems, we propose a novel deep learning-based interactive segmentation method that not only has high efficiency due to only requiring clicks as user inputs but also generalizes well to a range of previously unseen objects. Specifically, we first encode user-provided interior margin points via our proposed exponentialized geodesic distance that enables a CNN to achieve a good initial segmentation result of both previously seen and unseen objects, then we use a novel information fusion method that combines the initial segmentation with only few additional user clicks to efficiently obtain a refined segmentation. We validated our proposed framework through extensive experiments on 2D and 3D medical image segmentation tasks with a wide range of previous unseen objects that were not present in the training set. Experimental results showed that our proposed framework 1) achieves accurate results with fewer user interactions and less time compared with state-of-the-art interactive frameworks and 2) generalizes well to previously unseen objects.

Xiangde Luo, Tao Song, Guotai Wang et al.

Lung nodule detection from 3D Computed Tomography scans plays a vital role in efficient lung cancer screening. Despite the SOTA performance obtained by recent anchor-based detectors using CNNs for this task, they require predetermined anchor parameters such as the size, number, and aspect ratio of anchors, and have limited robustness when dealing with lung nodules with a massive variety of sizes. To overcome these problems, we propose a 3D sphere representation-based center-points matching detection network that is anchor-free and automatically predicts the position, radius, and offset of nodules without the manual design of nodule/anchor parameters. The SCPM-Net consists of two novel components: sphere representation and center points matching. First, to match the nodule annotation in clinical practice, we replace the commonly used bounding box with our proposed bounding sphere to represent nodules with the centroid, radius, and local offset in 3D space. A compatible sphere-based intersection over-union loss function is introduced to train the lung nodule detection network stably and efficiently. Second, we empower the network anchor-free by designing a positive center-points selection and matching process, which naturally discards pre-determined anchor boxes. An online hard example mining and re-focal loss subsequently enable the CPM process to be more robust, resulting in more accurate point assignment and mitigation of class imbalance. In addition, to better capture spatial information and 3D context for the detection, we propose to fuse multi-level spatial coordinate maps with the feature extractor and combine them with 3D squeeze-and-excitation attention modules. Experimental results on the LUNA16 dataset showed that our proposed framework achieves superior performance compared with existing anchor-based and anchor-free methods for lung nodule detection.

Xiangde Luo, Wenjun Liao, Jieneng Chen et al.

Gross Target Volume (GTV) segmentation plays an irreplaceable role in radiotherapy planning for Nasopharyngeal Carcinoma (NPC). Despite that Convolutional Neural Networks (CNN) have achieved good performance for this task, they rely on a large set of labeled images for training, which is expensive and time-consuming to acquire. In this paper, we propose a novel framework with Uncertainty Rectified Pyramid Consistency (URPC) regularization for semi-supervised NPC GTV segmentation. Concretely, we extend a backbone segmentation network to produce pyramid predictions at different scales. The pyramid predictions network (PPNet) is supervised by the ground truth of labeled images and a multi-scale consistency loss for unlabeled images, motivated by the fact that prediction at different scales for the same input should be similar and consistent. However, due to the different resolution of these predictions, encouraging them to be consistent at each pixel directly has low robustness and may lose some fine details. To address this problem, we further design a novel uncertainty rectifying module to enable the framework to gradually learn from meaningful and reliable consensual regions at different scales. Experimental results on a dataset with 258 NPC MR images showed that with only 10% or 20% images labeled, our method largely improved the segmentation performance by leveraging the unlabeled images, and it also outperformed five state-of-the-art semi-supervised segmentation methods. Moreover, when only 50% images labeled, URPC achieved an average Dice score of 82.74% that was close to fully supervised learning.