Yanfan Zhu

Leiyue Zhao, Tianyu Shi, Daniel Reisenbuchler et al.

Instance-level quantification of kidney functional units is essential for morphometric analysis, yet most publicly available pathology datasets provide only semantic segmentation annotations, where adjacent structures of the same class are merged into single regions. This prevents reliable instance-level analysis and limits downstream quantitative studies. Existing heuristic post-processing methods often yield suboptimal instance separation, particularly in crowded and adherent regions, while deep learning-based instance segmentation approaches typically require intensive instance-level annotations that are costly and labor-intensive to obtain. We propose MORI-Seg, a deep learning framework that enables instance segmentation without requiring instance-level annotations. Instead of heuristic splitting or instance supervision, MORI-Seg learns morphology-aware geometric representations directly from semantic masks by jointly modeling object-centric distance fields and boundary-band representations to encode interior structure and contact interfaces. A class-conditioned feature disentanglement module further promotes intra-instance coherence and inter-instance separation. Under semantic-only supervision, MORI-Seg decomposes connected semantic regions into distinct instance masks in an end-to-end manner. Experiments demonstrate improved instance separation accuracy and more reliable morphometric quantification compared with classical post-processing pipelines and representative semantic-to-instance learning approaches. The official implementation is publicly available at https://github.com/ddrrnn123/MORI-Seg.

Junchao Zhu, Ruining Deng, Junlin Guo et al.

Inferring spatially resolved gene expression from histology images offers a cost-effective complement to spatial transcriptomics (ST). However, existing methods reduce this task to a simple morphology-to-expression mapping, where visual similarity does not guarantee molecular consistency. Meanwhile, single-cell data has amassed rich resources far surpassing the scale of ST data, yet it remains underexplored in vision-omics modeling. Furthermore, current approaches commit to a monolithic paradigm with bottlenecks, unable to balance expressive flexibility with biological fidelity. To bridge these gaps, we propose DUET, a novel dual-paradigm framework that synergizes parametric prediction and memory-based retrieval under cellular inductive priors. DUET implements a parallel regression-retrieval paradigm, adaptively reconciling the outputs of its complementary pathways. To mitigate aleatoric vision ambiguity, we incorporate large-scale single-cell references to impose molecular states as biological constraints for faithful learning. Building upon structural refinement, we further design a lightweight adapter to dynamically assign branch preference across spatial contexts to achieve optimal performance. Extensive experiments on three public datasets across varied gene scales demonstrate that DUET achieves SOTA performance, with consistent gains contributed by each proposed component. Code is available at https://github.com/Junchao-Zhu/DUET

Yuechen Yang, Junlin Guo, Yanfan Zhu et al.

High-throughput "pathomic" analysis of Whole Slide Images (WSIs) offers new opportunities to study tissue characteristics and for biomarker discovery. However, the clinical relevance of the tissue characteristics at the micro- and macro-environment level is limited by the lack of tools that facilitate the measurement of the spatial interaction of individual structure characteristics and their association with clinical parameters. To address these challenges, we introduce HistoWAS (Histology-Wide Association Study), a computational framework designed to link tissue spatial organization to clinical outcomes. Specifically, HistoWAS implements (1) a feature space that augments conventional metrics with 30 topological and spatial features, adapted from Geographic Information Systems (GIS) point pattern analysis, to quantify tissue micro-architecture; and (2) an association study engine, inspired by Phenome-Wide Association Studies (PheWAS), that performs mass univariate regression for each feature with statistical correction. As a proof of concept, we applied HistoWAS to analyze a total of 102 features (72 conventional object-level features and our 30 spatial features) using 385 PAS-stained WSIs from 206 participants in the Kidney Precision Medicine Project (KPMP). The code and data have been released to https://github.com/hrlblab/histoWAS.

Zhengyi Lu, Ming Lu, Chongyu Qu et al.

Metal implants in MRI cause severe artifacts that degrade image quality and hinder clinical diagnosis. Traditional approaches address metal artifact reduction (MAR) and accelerated MRI acquisition as separate problems. We propose MASC, a unified reinforcement learning framework that jointly optimizes metal-aware k-space sampling and artifact correction for accelerated MRI. To enable supervised training, we construct a paired MRI dataset using physics-based simulation, generating k-space data and reconstructions for phantoms with and without metal implants. This paired dataset provides simulated 3D MRI scans with and without metal implants, where each metal-corrupted sample has an exactly matched clean reference, enabling direct supervision for both artifact reduction and acquisition policy learning. We formulate active MRI acquisition as a sequential decision-making problem, where an artifact-aware Proximal Policy Optimization (PPO) agent learns to select k-space phase-encoding lines under a limited acquisition budget. The agent operates on undersampled reconstructions processed through a U-Net-based MAR network, learning patterns that maximize reconstruction quality. We further propose an end-to-end training scheme where the acquisition policy learns to select k-space lines that best support artifact removal while the MAR network simultaneously adapts to the resulting undersampling patterns. Experiments demonstrate that MASC's learned policies outperform conventional sampling strategies, and end-to-end training improves performance compared to using a frozen pre-trained MAR network, validating the benefit of joint optimization. Cross-dataset experiments on FastMRI with physics-based artifact simulation further confirm generalization to realistic clinical MRI data. The code and models of MASC have been made publicly available: https://github.com/hrlblab/masc

Yuechen Yang, Junlin Guo, Ruining Deng et al.

Pathomics is a recent approach that offers rich quantitative features beyond what black-box deep learning can provide, supporting more reproducible and explainable biomarkers in digital pathology. However, many derived features (e.g., "second-order moment") remain difficult to interpret, especially across different clinical contexts, which limits their practical adoption. Conditional diffusion models show promise for explainability through feature editing, but they typically assume feature independence**--**an assumption violated by intrinsically correlated pathomics features. Consequently, editing one feature while fixing others can push the model off the biological manifold and produce unrealistic artifacts. To address this, we propose a Manifold-Aware Diffusion (MAD) framework for controllable and biologically plausible cell nuclei editing. Unlike existing approaches, our method regularizes feature trajectories within a disentangled latent space learned by a variational auto-encoder (VAE). This ensures that manipulating a target feature automatically adjusts correlated attributes to remain within the learned distribution of real cells. These optimized features then guide a conditional diffusion model to synthesize high-fidelity images. Experiments demonstrate that our approach is able to navigate the manifold of pathomics features when editing those features. The proposed method outperforms baseline methods in conditional feature editing while preserving structural coherence.

Chongyu Qu, Can Cui, Zhengyi Lu et al.

Does every cancer patient truly need a complete diagnostic workup for accurate survival prediction? In multimodal clinical oncology, diagnostic modalities follow a clinically mandated order of escalating burden -- from demographics collected at intake to genomic profiling requiring specialized tissue analysis. Current multimodal survival methods either assume all modalities are available or passively handle missing data, but none actively reason about whether acquiring the next modality is justified for a given patient along this ordered workflow. We formulate this as a sequential decision problem and propose SAGEAgent (Sequential Acquisition Guided by Experience), a self-evolving LLM-based clinical agent that decides which diagnostic modalities to acquire for each patient, balancing predictive accuracy against clinical invasiveness. SAGEAgent reasons about each patient's evolving diagnostic state through clinical tools that translate numerical predictions into text, an episodic memory that retrieves similar past cases, and a semantic memory that accumulates reusable decision patterns from experience. Experiments on a glioma cohort combining TCGA-LGG, TCGA-GBM, and BraTS with four diagnostic modalities demonstrate that SAGEAgent achieves competitive survival prediction accuracy while reducing average acquisition burden by 55%.

Chongyu Qu, Zhengyi Lu, Yuxiang Lai et al.

Multimodal fusion has emerged as a promising paradigm for disease diagnosis and prognosis, integrating complementary information from heterogeneous data sources such as medical images, clinical records, and radiology reports. However, existing fusion methods process all available modalities through the network, either treating them equally or learning to assign different contribution weights, leaving a fundamental question unaddressed: for a given patient, should certain modalities be used at all? We present AdaFuse, an adaptive multimodal fusion framework that leverages reinforcement learning (RL) to learn patient-specific modality selection and fusion strategies for lung cancer risk prediction. AdaFuse formulates multimodal fusion as a sequential decision process, where the policy network iteratively decides whether to incorporate an additional modality or proceed to prediction based on the information already acquired. This sequential formulation enables the model to condition each selection on previously observed modalities and terminate early when sufficient information is available, rather than committing to a fixed subset upfront. We evaluate AdaFuse on the National Lung Screening Trial (NLST) dataset. Experimental results demonstrate that AdaFuse achieves the highest AUC (0.762) compared to the best single-modality baseline (0.732), the best fixed fusion strategy (0.759), and adaptive baselines including DynMM (0.754) and MoE (0.742), while using fewer FLOPs than all triple-modality methods. Our work demonstrates the potential of reinforcement learning for personalized multimodal fusion in medical imaging, representing a shift from uniform fusion strategies toward adaptive diagnostic pipelines that learn when to consult additional modalities and when existing information suffices for accurate prediction.