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Xiangde Luo

Publications and source records attributed to Xiangde Luo.

At least 19 recordsLinked to original sources

A Multimodal Foundation Model of Spatial Transcriptomics and Histology for Biological Discovery and Clinical Prediction

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.

cs.AI

A Generative Foundation Model for Multimodal Histopathology

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 Fr\'echet 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.

cs.CV

A3-TTA: Adaptive Anchor Alignment Test-Time Adaptation for Image Segmentation

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.

cs.CV

nnMIL: A generalizable multiple instance learning framework for computational pathology

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 present nnMIL, a simple yet broadly applicable multiple-instance learning framework that connects patch-level foundation models to robust slide-level clinical prediction. 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.

cs.CV

MedSeqFT: Sequential Fine-tuning Foundation Models for 3D Medical Image Segmentation

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.

cs.CV

A Generative Foundation Model for Chest Radiography

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.

cs.CV

Ensemble learning of pathology foundation models for precision oncology

Histopathology is essential for cancer diagnosis and treatment selection, and pathology foundation models learn visual representations from whole-slide images (WSIs). However, existing foundation models are trained on disparate datasets using varying strategies, leading to inconsistent performance and limited generalizability. Here, we introduce ELF (Ensemble Learning of Foundation models), which integrates five pretrained pathology foundation models into unified slide-level representations. Trained on 53,699 WSIs spanning 20 anatomical sites, ELF leverages ensemble learning to capture complementary information across models. ELF's slide-level architecture is designed for data-efficient downstream evaluation, including settings with limited data such as therapeutic response prediction. We evaluate ELF for disease classification, biomarker detection, as well as anticancer and immunotherapy response prediction across multiple cancer types. ELF achieves higher performance than the evaluated constituent and slide-level foundation models across the tested tasks, supporting further evaluation of ensemble learning for pathology applications in oncology.

cs.CV

DiffOSeg: Omni Medical Image Segmentation via Multi-Expert Collaboration Diffusion Model

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 .

cs.CV

Dynamic Gradient Sparsification Training for Few-Shot Fine-tuning of CT Lymph Node Segmentation Foundation Model

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.

cs.CV

Self-Consistent Nested Diffusion Bridge for Accelerated MRI Reconstruction

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.

eess.IV

Learning Modality-Aware Representations: Adaptive Group-wise Interaction Network for Multimodal MRI Synthesis

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.

eess.IV

Weakly Supervised Lymph Nodes Segmentation Based on Partial Instance Annotations with Pre-trained Dual-branch Network and Pseudo Label Learning

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

cs.CV

SAM-Driven Weakly Supervised Nodule Segmentation with Uncertainty-Aware Cross Teaching

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.

cs.CV

An Uncertainty-guided Tiered Self-training Framework for Active Source-free Domain Adaptation in Prostate Segmentation

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

cs.CV

Advancing UWF-SLO Vessel Segmentation with Source-Free Active Domain Adaptation and a Novel Multi-Center Dataset

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.

eess.IV

Rethinking Abdominal Organ Segmentation (RAOS) in the clinical scenario: A robustness evaluation benchmark with challenging cases

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}.

eess.IV

Ultrasound Nodule Segmentation Using Asymmetric Learning with Simple Clinical Annotation

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.

cs.CV

Diversified and Personalized Multi-rater Medical Image Segmentation

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.

cs.CV