Ran Su

Tianling Liu, Ran Su, Changming Sun et al.

Ovarian cancer is one of the most serious cancers that threaten women around the world. Epithelial ovarian cancer (EOC), as the most commonly seen subtype of ovarian cancer, has rather high mortality rate and poor prognosis among various gynecological cancers. Survival analysis outcome is able to provide treatment advices to doctors. In recent years, with the development of medical imaging technology, survival prediction approaches based on pathological images have been proposed. In this study, we designed a deep framework named EOCSA which analyzes the prognosis of EOC patients based on pathological whole slide images (WSIs). Specifically, we first randomly extracted patches from WSIs and grouped them into multiple clusters. Next, we developed a survival prediction model, named DeepConvAttentionSurv (DCAS), which was able to extract patch-level features, removed less discriminative clusters and predicted the EOC survival precisely. Particularly, channel attention, spatial attention, and neuron attention mechanisms were used to improve the performance of feature extraction. Then patient-level features were generated from our weight calculation method and the survival time was finally estimated using LASSO-Cox model. The proposed EOCSA is efficient and effective in predicting prognosis of EOC and the DCAS ensures more informative and discriminative features can be extracted. As far as we know, our work is the first to analyze the survival of EOC based on WSIs and deep neural network technologies. The experimental results demonstrate that our proposed framework has achieved state-of-the-art performance of 0.980 C-index. The implementation of the approach can be found at https://github.com/RanSuLab/EOCprognosis.

Qiangguo Jin, Xianyao Zheng, Hui Cui et al.

Medical visual question answering (Med-VQA) is a crucial multimodal task in clinical decision support and telemedicine. Recent self-attention based methods struggle to effectively handle cross-modal semantic alignments between vision and language. Moreover, classification-based methods rely on predefined answer sets. Treating this task as a simple classification problem may make it unable to adapt to the diversity of free-form answers and overlook the detailed semantic information of free-form answers. In order to tackle these challenges, we introduce a Cross-Mamba Interaction based Multi-Task Learning (CMI-MTL) framework that learns cross-modal feature representations from images and texts. CMI-MTL comprises three key modules: fine-grained visual-text feature alignment (FVTA), cross-modal interleaved feature representation (CIFR), and free-form answer-enhanced multi-task learning (FFAE). FVTA extracts the most relevant regions in image-text pairs through fine-grained visual-text feature alignment. CIFR captures cross-modal sequential interactions via cross-modal interleaved feature representation. FFAE leverages auxiliary knowledge from open-ended questions through free-form answer-enhanced multi-task learning, improving the model's capability for open-ended Med-VQA. Experimental results show that CMI-MTL outperforms the existing state-of-the-art methods on three Med-VQA datasets: VQA-RAD, SLAKE, and OVQA. Furthermore, we conduct more interpretability experiments to prove the effectiveness. The code is publicly available at https://github.com/BioMedIA-repo/CMI-MTL.

Chao Pang, Yu Wang, Yi Jiang et al.

In this work, we propose MEDICO, a Multi-viEw Deep generative model for molecule generation, structural optimization, and the SARS-CoV-2 Inhibitor disCOvery. To the best of our knowledge, MEDICO is the first-of-this-kind graph generative model that can generate molecular graphs similar to the structure of targeted molecules, with a multi-view representation learning framework to sufficiently and adaptively learn comprehensive structural semantics from targeted molecular topology and geometry. We show that our MEDICO significantly outperforms the state-of-the-art methods in generating valid, unique, and novel molecules under benchmarking comparisons. In particular, we showcase the multi-view deep learning model enables us to generate not only the molecules structurally similar to the targeted molecules but also the molecules with desired chemical properties, demonstrating the strong capability of our model in exploring the chemical space deeply. Moreover, case study results on targeted molecule generation for the SARS-CoV-2 main protease (Mpro) show that by integrating molecule docking into our model as chemical priori, we successfully generate new small molecules with desired drug-like properties for the Mpro, potentially accelerating the de novo design of Covid-19 drugs. Further, we apply MEDICO to the structural optimization of three well-known Mpro inhibitors (N3, 11a, and GC376) and achieve ~88% improvement in their binding affinity to Mpro, demonstrating the application value of our model for the development of therapeutics for SARS-CoV-2 infection.

Linkuan Zhou, Yinghao Xia, Yufei Shen et al.

Unsupervised Domain Adaptation (UDA) is essential for deploying medical segmentation models across diverse clinical environments. Existing methods are fundamentally limited, suffering from semantically unaware feature alignment that results in poor distributional fidelity and from pseudo-label validation that disregards global anatomical constraints, thus failing to prevent the formation of globally implausible structures. To address these issues, we propose SHAPE (Structure-aware Hierarchical Unsupervised Domain Adaptation with Plausibility Evaluation), a framework that reframes adaptation towards global anatomical plausibility. Built on a DINOv3 foundation, its Hierarchical Feature Modulation (HFM) module first generates features with both high fidelity and class-awareness. This shifts the core challenge to robustly validating pseudo-labels. To augment conventional pixel-level validation, we introduce Hypergraph Plausibility Estimation (HPE), which leverages hypergraphs to assess the global anatomical plausibility that standard graphs cannot capture. This is complemented by Structural Anomaly Pruning (SAP) to purge remaining artifacts via cross-view stability. SHAPE significantly outperforms prior methods on cardiac and abdominal cross-modality benchmarks, achieving state-of-the-art average Dice scores of 90.08% (MRI->CT) and 78.51% (CT->MRI) on cardiac data, and 87.48% (MRI->CT) and 86.89% (CT->MRI) on abdominal data. The code is available at https://github.com/BioMedIA-repo/SHAPE.

Gaochao Song, Luo Zhang, Ran Su et al.

Implicit neural representation (INR) is a popular approach for arbitrary-scale image super-resolution (SR), as a key component of INR, position encoding improves its representation ability. Motivated by position encoding, we propose orthogonal position encoding (OPE) - an extension of position encoding - and an OPE-Upscale module to replace the INR-based upsampling module for arbitrary-scale image super-resolution. Same as INR, our OPE-Upscale Module takes 2D coordinates and latent code as inputs; however it does not require training parameters. This parameter-free feature allows the OPE-Upscale Module to directly perform linear combination operations to reconstruct an image in a continuous manner, achieving an arbitrary-scale image reconstruction. As a concise SR framework, our method has high computing efficiency and consumes less memory comparing to the state-of-the-art (SOTA), which has been confirmed by extensive experiments and evaluations. In addition, our method has comparable results with SOTA in arbitrary scale image super-resolution. Last but not the least, we show that OPE corresponds to a set of orthogonal basis, justifying our design principle.

Xianyao Zheng, Hong Yu, Hui Cui et al.

Medical visual question answering (Med-VQA) is a crucial multimodal task in clinical decision support and telemedicine. Recent methods fail to fully leverage domain-specific medical knowledge, making it difficult to accurately associate lesion features in medical images with key diagnostic criteria. Additionally, classification-based approaches typically rely on predefined answer sets. Treating Med-VQA as a simple classification problem limits its ability to adapt to the diversity of free-form answers and may overlook detailed semantic information in those answers. To address these challenges, we propose a knowledge graph enhanced cross-Mamba interaction (KG-CMI) framework, which consists of a fine-grained cross-modal feature alignment (FCFA) module, a knowledge graph embedding (KGE) module, a cross-modal interaction representation (CMIR) module, and a free-form answer enhanced multi-task learning (FAMT) module. The KG-CMI learns cross-modal feature representations for images and texts by effectively integrating professional medical knowledge through a graph, establishing associations between lesion features and disease knowledge. Moreover, FAMT leverages auxiliary knowledge from open-ended questions, improving the model's capability for open-ended Med-VQA. Experimental results demonstrate that KG-CMI outperforms existing state-of-the-art methods on three Med-VQA datasets, i.e., VQA-RAD, SLAKE, and OVQA. Additionally, we conduct interpretability experiments to further validate the framework's effectiveness.

Xiangyu Li, Ran Su

Multiple instance learning (MIL) is the standard approach for whole-slide image (WSI) classification and survival prediction, where attention-based models ag gregate patch features into slide-level predictions. These models treat attention weights as evidence for their predictions, but attention is optimized for classi fication, not for identifying which patches actually support the diagnosis. This conflation leads to three failures: selected patches are insufficient (keeping them alone drops Macro-F1 by 0.078), unnecessary (removing them barely changes the prediction), and unrecoverable (continuous attention scores disagree with discrete patch subsets used at inference). The central premise is that evidence quality should be optimized directly through explicit criteria- Sufficiency, Necessity, and Recov erability (S/N/R)- rather than inherited as a byproduct of classification. GCE-MIL is a backbone-agnostic wrapper implemented through three injection modes and three evidence components: a grounding mechanism that aligns selection with domain-specific concepts, noisy-OR coverage that acts as a differentiable proxy for interventional evidence search, and threshold-plus-repair recovery that converts continuous selectors into discrete subsets through marginal-guided repair. Across 9 backbones and 9 datasets (81 configurations), GCE-MIL improves average Macro-F1 by 0.024 and C-index by 0.014, reduces the continuous-discrete gap by 4-7, and increases complement degradation by 2-4. With optional tile prefiltering after discrete recovery, inference runs up to 5 faster while retaining 0.989 full-bag utility.

Xiangyu Li, Ran Su

Whole-slide MIL models are often called context-aware once graphs, Transform ers, or state-space modules are placed above patch embeddings. We show that this label can be deceptive. On pathology tasks where tissue architecture is part of the diagnostic signal, several strong MIL baselines retain nearly unchanged slide level AUC after patch coordinates are permuted. Their predictions are accurate, but largely compositional. We refer to this failure mode as spatial blindness. Our explanation is optimization-based: dense appearance statistics are learned early under slide-level supervision, leaving weak gradients for sparse spatial relations. ResTopoMIL addresses the issue by first fitting a permutation-invariant prototype histogram and then freezing it while a lightweight graph branch learns the residual under a coordinate-shuffling constraint. The architecture is simple by design; the intervention is in how the spatial branch is trained. Across 9 public WSI bench marks, ResTopoMIL improves classification and survival prediction with 1.15M parameters, restores sensitivity to coordinate perturbation, and gives stronger lo calization evidence on CAMELYON-16.

Qiangguo Jin, Hui Cui, Junbo Wang et al.

Semi-supervised learning (SSL) has attracted considerable attention in medical image processing. The latest SSL methods use a combination of consistency regularization and pseudo-labeling to achieve remarkable success. However, most existing SSL studies focus on segmenting large organs, neglecting the challenging scenarios where there are numerous tumors or tumors of small volume. Furthermore, the extensive capabilities of data augmentation strategies, particularly in the context of both labeled and unlabeled data, have yet to be thoroughly investigated. To tackle these challenges, we introduce a straightforward yet effective approach, termed iterative pseudo-labeling based adaptive copy-paste supervision (IPA-CP), for tumor segmentation in CT scans. IPA-CP incorporates a two-way uncertainty based adaptive augmentation mechanism, aiming to inject tumor uncertainties present in the mean teacher architecture into adaptive augmentation. Additionally, IPA-CP employs an iterative pseudo-label transition strategy to generate more robust and informative pseudo labels for the unlabeled samples. Extensive experiments on both in-house and public datasets show that our framework outperforms state-of-the-art SSL methods in medical image segmentation. Ablation study results demonstrate the effectiveness of our technical contributions.

Linkuan Zhou, Zhexin Chen, Yufei Shen et al.

Automated segmentation of the fetal head in ultrasound images is critical for prenatal monitoring. However, achieving robust segmentation remains challenging due to the poor quality of ultrasound images and the lack of annotated data. Semi-supervised methods alleviate the lack of annotated data but struggle with the unique characteristics of fetal head ultrasound images, making it challenging to generate reliable pseudo-labels and enforce effective consistency regularization constraints. To address this issue, we propose a novel semi-supervised framework, ERSR, for fetal head ultrasound segmentation. Our framework consists of the dual-scoring adaptive filtering strategy, the ellipse-constrained pseudo-label refinement, and the symmetry-based multiple consistency regularization. The dual-scoring adaptive filtering strategy uses boundary consistency and contour regularity criteria to evaluate and filter teacher outputs. The ellipse-constrained pseudo-label refinement refines these filtered outputs by fitting least-squares ellipses, which strengthens pixels near the center of the fitted ellipse and suppresses noise simultaneously. The symmetry-based multiple consistency regularization enforces multi-level consistency across perturbed images, symmetric regions, and between original predictions and pseudo-labels, enabling the model to capture robust and stable shape representations. Our method achieves state-of-the-art performance on two benchmarks. On the HC18 dataset, it reaches Dice scores of 92.05% and 95.36% with 10% and 20% labeled data, respectively. On the PSFH dataset, the scores are 91.68% and 93.70% under the same settings.

Ran Su, Rui Shi, Hui Cui et al.

Molecular subtyping of cancer is recognized as a critical and challenging upstream task for personalized therapy. Existing deep learning methods have achieved significant performance in this domain when abundant data samples are available. However, the acquisition of densely labeled samples for cancer molecular subtypes remains a significant challenge for conventional data-intensive deep learning approaches. In this work, we focus on the few-shot molecular subtype prediction problem in heterogeneous and small cancer datasets, aiming to enhance precise diagnosis and personalized treatment. We first construct a new few-shot dataset for cancer molecular subtype classification and auxiliary cancer classification, named TCGA Few-Shot, from existing publicly available datasets. To effectively leverage the relevant knowledge from both tasks, we introduce a task-specific embedding-based meta-learning framework (TSEML). TSEML leverages the synergistic strengths of a model-agnostic meta-learning (MAML) approach and a prototypical network (ProtoNet) to capture diverse and fine-grained features. Comparative experiments conducted on the TCGA Few-Shot dataset demonstrate that our TSEML framework achieves superior performance in addressing the problem of few-shot molecular subtype classification.

Qiangguo Jin, Jiapeng Huang, Changming Sun et al.

The precise diagnosis of urinary stones is crucial for devising effective treatment strategies. The diagnostic process, however, is often complicated by the low contrast between stones and surrounding tissues, as well as the variability in stone locations across different patients. To address this issue, we propose a novel location embedding based pairwise distance learning network (LEPD-Net) that leverages low-dose abdominal X-ray imaging combined with location information for the fine-grained diagnosis of urinary stones. LEPD-Net enhances the representation of stone-related features through context-aware region enhancement, incorporates critical location knowledge via stone location embedding, and achieves recognition of fine-grained objects with our innovative fine-grained pairwise distance learning. Additionally, we have established an in-house dataset on urinary tract stones to demonstrate the effectiveness of our proposed approach. Comprehensive experiments conducted on this dataset reveal that our framework significantly surpasses existing state-of-the-art methods.

Qiangguo Jin, Hui Cui, Changming Sun et al.

Acquiring pixel-level annotations is often limited in applications such as histology studies that require domain expertise. Various semi-supervised learning approaches have been developed to work with limited ground truth annotations, such as the popular teacher-student models. However, hierarchical prediction uncertainty within the student model (intra-uncertainty) and image prediction uncertainty (inter-uncertainty) have not been fully utilized by existing methods. To address these issues, we first propose a novel inter- and intra-uncertainty regularization method to measure and constrain both inter- and intra-inconsistencies in the teacher-student architecture. We also propose a new two-stage network with pseudo-mask guided feature aggregation (PG-FANet) as the segmentation model. The two-stage structure complements with the uncertainty regularization strategy to avoid introducing extra modules in solving uncertainties and the aggregation mechanisms enable multi-scale and multi-stage feature integration. Comprehensive experimental results over the MoNuSeg and CRAG datasets show that our PG-FANet outperforms other state-of-the-art methods and our semi-supervised learning framework yields competitive performance with a limited amount of labeled data.

Qiangguo Jin, Hui Cui, Changming Sun et al.

The insufficiency of annotated medical imaging scans for cancer makes it challenging to train and validate data-hungry deep learning models in precision oncology. We propose a new richer generative adversarial network for free-form 3D tumor/lesion synthesis in computed tomography (CT) images. The network is composed of a new richer convolutional feature enhanced dilated-gated generator (RicherDG) and a hybrid loss function. The RicherDG has dilated-gated convolution layers to enable tumor-painting and to enlarge perceptive fields; and it has a novel richer convolutional feature association branch to recover multi-scale convolutional features especially from uncertain boundaries between tumor and surrounding healthy tissues. The hybrid loss function, which consists of a diverse range of losses, is designed to aggregate complementary information to improve optimization. We perform a comprehensive evaluation of the synthesis results on a wide range of public CT image datasets covering the liver, kidney tumors, and lung nodules. The qualitative and quantitative evaluations and ablation study demonstrated improved synthesizing results over advanced tumor synthesis methods.

Qiangguo Jin, Hui Cui, Changming Sun et al.

The capability of generalization to unseen domains is crucial for deep learning models when considering real-world scenarios. However, current available medical image datasets, such as those for COVID-19 CT images, have large variations of infections and domain shift problems. To address this issue, we propose a prior knowledge driven domain adaptation and a dual-domain enhanced self-correction learning scheme. Based on the novel learning schemes, a domain adaptation based self-correction model (DASC-Net) is proposed for COVID-19 infection segmentation on CT images. DASC-Net consists of a novel attention and feature domain enhanced domain adaptation model (AFD-DA) to solve the domain shifts and a self-correction learning process to refine segmentation results. The innovations in AFD-DA include an image-level activation feature extractor with attention to lung abnormalities and a multi-level discrimination module for hierarchical feature domain alignment. The proposed self-correction learning process adaptively aggregates the learned model and corresponding pseudo labels for the propagation of aligned source and target domain information to alleviate the overfitting to noises caused by pseudo labels. Extensive experiments over three publicly available COVID-19 CT datasets demonstrate that DASC-Net consistently outperforms state-of-the-art segmentation, domain shift, and coronavirus infection segmentation methods. Ablation analysis further shows the effectiveness of the major components in our model. The DASC-Net enriches the theory of domain adaptation and self-correction learning in medical imaging and can be generalized to multi-site COVID-19 infection segmentation on CT images for clinical deployment.

Qiangguo Jin, Zhaopeng Meng, Changming Sun et al.

Automatic extraction of liver and tumor from CT volumes is a challenging task due to their heterogeneous and diffusive shapes. Recently, 2D and 3D deep convolutional neural networks have become popular in medical image segmentation tasks because of the utilization of large labeled datasets to learn hierarchical features. However, 3D networks have some drawbacks due to their high cost on computational resources. In this paper, we propose a 3D hybrid residual attention-aware segmentation method, named RA-UNet, to precisely extract the liver volume of interests (VOI) and segment tumors from the liver VOI. The proposed network has a basic architecture as a 3D U-Net which extracts contextual information combining low-level feature maps with high-level ones. Attention modules are stacked so that the attention-aware features change adaptively as the network goes "very deep" and this is made possible by residual learning. This is the first work that an attention residual mechanism is used to process medical volumetric images. We evaluated our framework on the public MICCAI 2017 Liver Tumor Segmentation dataset and the 3DIRCADb dataset. The results show that our architecture outperforms other state-of-the-art methods. We also extend our RA-UNet to brain tumor segmentation on the BraTS2018 and BraTS2017 datasets, and the results indicate that RA-UNet achieves good performance on a brain tumor segmentation task as well.

Qiangguo Jin, Zhaopeng Meng, Tuan D. Pham et al.

Automatic segmentation of retinal vessels in fundus images plays an important role in the diagnosis of some diseases such as diabetes and hypertension. In this paper, we propose Deformable U-Net (DUNet), which exploits the retinal vessels' local features with a U-shape architecture, in an end to end manner for retinal vessel segmentation. Inspired by the recently introduced deformable convolutional networks, we integrate the deformable convolution into the proposed network. The DUNet, with upsampling operators to increase the output resolution, is designed to extract context information and enable precise localization by combining low-level feature maps with high-level ones. Furthermore, DUNet captures the retinal vessels at various shapes and scales by adaptively adjusting the receptive fields according to vessels' scales and shapes. Three public datasets DRIVE, STARE and CHASE_DB1 are used to train and test our model. Detailed comparisons between the proposed network and the deformable neural network, U-Net are provided in our study. Results show that more detailed vessels are extracted by DUNet and it exhibits state-of-the-art performance for retinal vessel segmentation with a global accuracy of 0.9697/0.9722/0.9724 and AUC of 0.9856/0.9868/0.9863 on DRIVE, STARE and CHASE_DB1 respectively. Moreover, to show the generalization ability of the DUNet, we used another two retinal vessel data sets, one is named WIDE and the other is a synthetic data set with diverse styles, named SYNTHE, to qualitatively and quantitatively analyzed and compared with other methods. Results indicates that DUNet outperforms other state-of-the-arts.