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Ruijiang Li

Publications and source records attributed to Ruijiang Li.

15 recordsLinked to original sources

SP-Mind: An Autonomous Reasoning Agent for Spatial Proteomics Analysis

Spatial proteomics enables single-cell-resolution characterization of protein expression within tissue architecture, playing a critical role in understanding tumor microenvironments and guiding precision medicine. However, current analysis workflows remain fragmented, requiring expert manual orchestration of heterogeneous tools and limiting research scalability and reproducibility. We present SP-Mind, the first autonomous AI agent designed to unify the spatial proteomics analysis pipeline, from raw multiplexed tissue imaging to downstream phenotype discovery. Equipped with expert-curated biological analysis skills and specialized computational tools, SP-Mind converts natural-language queries into end-to-end analytical workflows without task-specific fine-tuning. To rigorously evaluate its capabilities, we introduce SP-Bench, a comprehensive benchmark spanning diverse tissue types, comprising 102 tasks across 18 distinct categories. Through extensive evaluation on SP-Bench and established downstream tasks, SP-Mind achieves state-of-the-art performance compared to existing open-source biomedical agent baselines. Code is publicly available at https://github.com/tomtommyyuan/spmind.

cs.AI

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

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

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

Memory Efficient Temporal & Visual Graph Model for Unsupervised Video Domain Adaptation

Existing video domain adaption (DA) methods need to store all temporal combinations of video frames or pair the source and target videos, which are memory cost expensive and can't scale up to long videos. To address these limitations, we propose a memory-efficient graph-based video DA approach as follows. At first our method models each source or target video by a graph: nodes represent video frames and edges represent the temporal or visual similarity relationship between frames. We use a graph attention network to learn the weight of individual frames and simultaneously align the source and target video into a domain-invariant graph feature space. Instead of storing a large number of sub-videos, our method only constructs one graph with a graph attention mechanism for one video, reducing the memory cost substantially. The extensive experiments show that, compared with the state-of-art methods, we achieved superior performance while reducing the memory cost significantly.

cs.CV

A Privacy-Preserving Unsupervised Domain Adaptation Framework for Clinical Text Analysis

Unsupervised domain adaptation (UDA) generally aligns the unlabeled target domain data to the distribution of the source domain to mitigate the distribution shift problem. The standard UDA requires sharing the source data with the target, having potential data privacy leaking risks. To protect the source data's privacy, we first propose to share the source feature distribution instead of the source data. However, sharing only the source feature distribution may still suffer from the membership inference attack who can infer an individual's membership by the black-box access to the source model. To resolve this privacy issue, we further study the under-explored problem of privacy-preserving domain adaptation and propose a method with a novel differential privacy training strategy to protect the source data privacy. We model the source feature distribution by Gaussian Mixture Models (GMMs) under the differential privacy setting and send it to the target client for adaptation. The target client resamples differentially private source features from GMMs and adapts on target data with several state-of-art UDA backbones. With our proposed method, the source data provider could avoid leaking source data privacy during domain adaptation as well as reserve the utility. To evaluate our proposed method's utility and privacy loss, we apply our model on a medical report disease label classification task using two noisy challenging clinical text datasets. The results show that our proposed method can preserve source data's privacy with a minor performance influence on the text classification task.

cs.CL

Relation Embedding with Dihedral Group in Knowledge Graph

Link prediction is critical for the application of incomplete knowledge graph (KG) in the downstream tasks. As a family of effective approaches for link predictions, embedding methods try to learn low-rank representations for both entities and relations such that the bilinear form defined therein is a well-behaved scoring function. Despite of their successful performances, existing bilinear forms overlook the modeling of relation compositions, resulting in lacks of interpretability for reasoning on KG. To fulfill this gap, we propose a new model called DihEdral, named after dihedral symmetry group. This new model learns knowledge graph embeddings that can capture relation compositions by nature. Furthermore, our approach models the relation embeddings parametrized by discrete values, thereby decrease the solution space drastically. Our experiments show that DihEdral is able to capture all desired properties such as (skew-) symmetry, inversion and (non-) Abelian composition, and outperforms existing bilinear form based approach and is comparable to or better than deep learning models such as ConvE.

cs.CL

Groupwise Constrained Reconstruction for Subspace Clustering

Reconstruction based subspace clustering methods compute a self reconstruction matrix over the samples and use it for spectral clustering to obtain the final clustering result. Their success largely relies on the assumption that the underlying subspaces are independent, which, however, does not always hold in the applications with increasing number of subspaces. In this paper, we propose a novel reconstruction based subspace clustering model without making the subspace independence assumption. In our model, certain properties of the reconstruction matrix are explicitly characterized using the latent cluster indicators, and the affinity matrix used for spectral clustering can be directly built from the posterior of the latent cluster indicators instead of the reconstruction matrix. Experimental results on both synthetic and real-world datasets show that the proposed model can outperform the state-of-the-art methods.

cs.LG

3D tumor localization through real-time volumetric x-ray imaging for lung cancer radiotherapy

Recently we have developed an algorithm for reconstructing volumetric images and extracting 3D tumor motion information from a single x-ray projection. We have demonstrated its feasibility using a digital respiratory phantom with regular breathing patterns. In this work, we present a detailed description and a comprehensive evaluation of the improved algorithm. The algorithm was improved by incorporating respiratory motion prediction. The accuracy and efficiency were then evaluated on 1) a digital respiratory phantom, 2) a physical respiratory phantom, and 3) five lung cancer patients. These evaluation cases include both regular and irregular breathing patterns that are different from the training dataset. For the digital respiratory phantom with regular and irregular breathing, the average 3D tumor localization error is less than 1 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for 3D tumor localization from each projection ranges between 0.19 and 0.26 seconds, for both regular and irregular breathing, which is about a 10% improvement over previously reported results. For the physical respiratory phantom, an average tumor localization error below 1 mm was achieved with an average computation time of 0.13 and 0.16 seconds on the same GPU card, for regular and irregular breathing, respectively. For the five lung cancer patients, the average tumor localization error is below 2 mm in both the axial and tangential directions. The average computation time on the same GPU card ranges between 0.26 and 0.34 seconds.

physics.med-ph

GPU-based Fast Low-dose Cone Beam CT Reconstruction via Total Variation

Cone-beam CT (CBCT) has been widely used in image guided radiation therapy (IGRT) to acquire updated volumetric anatomical information before treatment fractions for accurate patient alignment purpose. However, the excessive x-ray imaging dose from serial CBCT scans raises a clinical concern in most IGRT procedures. The excessive imaging dose can be effectively reduced by reducing the number of x-ray projections and/or lowering mAs levels in a CBCT scan. The goal of this work is to develop a fast GPU-based algorithm to reconstruct high quality CBCT images from undersampled and noisy projection data so as to lower the imaging dose. The CBCT is reconstructed by minimizing an energy functional consisting of a data fidelity term and a total variation regularization term. We developed a GPU-friendly version of the forward-backward splitting algorithm to solve this model. A multi-grid technique is also employed. We test our CBCT reconstruction algorithm on a digital NCAT phantom and a head-and-neck patient case. The performance under low mAs is also validated using a physical Catphan phantom and a head-and-neck Rando phantom. It is found that 40 x-ray projections are sufficient to reconstruct CBCT images with satisfactory quality for IGRT patient alignment purpose. Phantom experiments indicated that CBCT images can be successfully reconstructed with our algorithm under as low as 0.1 mAs/projection level. Comparing with currently widely used full-fan head-and-neck scanning protocol of about 360 projections with 0.4 mAs/projection, it is estimated that an overall 36 times dose reduction has been achieved with our algorithm. Moreover, the reconstruction time is about 130 sec on an NVIDIA Tesla C1060 GPU card, which is estimated ~100 times faster than similar iterative reconstruction approaches.

physics.med-ph

Real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy

Purpose: To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Methods: Given a set of volumetric images of a patient at N breathing phases as the training data, we perform deformable image registration between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, we can generate new DVFs, which, when applied on the reference image, lead to new volumetric images. We then can reconstruct a volumetric image from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. Our algorithm was implemented on graphics processing units (GPUs) to achieve real-time efficiency. We generated the training data using a realistic and dynamic mathematical phantom with 10 breathing phases. The testing data were 360 cone beam projections corresponding to one gantry rotation, simulated using the same phantom with a 50% increase in breathing amplitude. Results: The average relative image intensity error of the reconstructed volumetric images is 6.9% +/- 2.4%. The average 3D tumor localization error is 0.8 mm +/- 0.5 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for reconstructing a volumetric image from each projection is 0.24 seconds (range: 0.17 and 0.35 seconds). Conclusions: We have shown the feasibility of reconstructing volumetric images and localizing tumor positions in 3D in near real-time from a single x-ray image.

physics.med-ph

GPU-based Fast Cone Beam CT Reconstruction from Undersampled and Noisy Projection Data via Total Variation

Purpose: Cone-beam CT (CBCT) plays an important role in image guided radiation therapy (IGRT). However, the large radiation dose from serial CBCT scans in most IGRT procedures raises a clinical concern, especially for pediatric patients who are essentially excluded from receiving IGRT for this reason. The goal of this work is to develop a fast GPU-based algorithm to reconstruct CBCT from undersampled and noisy projection data so as to lower the imaging dose. Methods: The CBCT is reconstructed by minimizing an energy functional consisting of a data fidelity term and a total variation regularization term. We developed a GPU-friendly version of the forward-backward splitting algorithm to solve this model. A multi-grid technique is also employed. Results: It is found that 20~40 x-ray projections are sufficient to reconstruct images with satisfactory quality for IGRT. The reconstruction time ranges from 77 to 130 sec on a NVIDIA Tesla C1060 GPU card, depending on the number of projections used, which is estimated about 100 times faster than similar iterative reconstruction approaches. Moreover, phantom studies indicate that our algorithm enables the CBCT to be reconstructed under a scanning protocol with as low as 0.1 mAs/projection. Comparing with currently widely used full-fan head and neck scanning protocol of ~360 projections with 0.4 mAs/projection, it is estimated that an overall 36~72 times dose reduction has been achieved in our fast CBCT reconstruction algorithm. Conclusions: This work indicates that the developed GPU-based CBCT reconstruction algorithm is capable of lowering imaging dose considerably. The high computation efficiency in this algorithm makes the iterative CBCT reconstruction approach applicable in real clinical environments.

physics.med-ph

PCA-based lung motion model

Organ motion induced by respiration may cause clinically significant targeting errors and greatly degrade the effectiveness of conformal radiotherapy. It is therefore crucial to be able to model respiratory motion accurately. A recently proposed lung motion model based on principal component analysis (PCA) has been shown to be promising on a few patients. However, there is still a need to understand the underlying reason why it works. In this paper, we present a much deeper and detailed analysis of the PCA-based lung motion model. We provide the theoretical justification of the effectiveness of PCA in modeling lung motion. We also prove that under certain conditions, the PCA motion model is equivalent to 5D motion model, which is based on physiology and anatomy of the lung. The modeling power of PCA model was tested on clinical data and the average 3D error was found to be below 1 mm.

physics.med-ph