HistoWAS: A Pathomics Framework for Large-Scale Feature-Wide Association Studies of Tissue Topology and Patient Outcomes

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.

SCR2-ST: Combine Single Cell with Spatial Transcriptomics for Efficient Active Sampling via Reinforcement Learning

Spatial transcriptomics (ST) is an emerging technology that enables researchers to investigate the molecular relationships underlying tissue morphology. However, acquiring ST data remains prohibitively expensive, and traditional fixed-grid sampling strategies lead to redundant measurements of morphologically similar or biologically uninformative regions, thus resulting in scarce data that constrain current methods. The well-established single-cell sequencing field, however, could provide rich biological data as an effective auxiliary source to mitigate this limitation. To bridge these gaps, we introduce SCR2-ST, a unified framework that leverages single-cell prior knowledge to guide efficient data acquisition and accurate expression prediction. SCR2-ST integrates a single-cell guided reinforcement learning-based (SCRL) active sampling and a hybrid regression-retrieval prediction network SCR2Net. SCRL combines single-cell foundation model embeddings with spatial density information to construct biologically grounded reward signals, enabling selective acquisition of informative tissue regions under constrained sequencing budgets. SCR2Net then leverages the actively sampled data through a hybrid architecture combining regression-based modeling with retrieval-augmented inference, where a majority cell-type filtering mechanism suppresses noisy matches and retrieved expression profiles serve as soft labels for auxiliary supervision. We evaluated SCR2-ST on three public ST datasets, demonstrating SOTA performance in both sampling efficiency and prediction accuracy, particularly under low-budget scenarios. Code is publicly available at: https://github.com/hrlblab/SCR2ST

How Close Are We? Limitations and Progress of AI Models in Banff Lesion Scoring

The Banff Classification provides the global standard for evaluating renal transplant biopsies, yet its semi-quantitative nature, complex criteria, and inter-observer variability present significant challenges for computational replication. In this study, we explore the feasibility of approximating Banff lesion scores using existing deep learning models through a modular, rule-based framework. We decompose each Banff indicator - such as glomerulitis (g), peritubular capillaritis (ptc), and intimal arteritis (v) - into its constituent structural and inflammatory components, and assess whether current segmentation and detection tools can support their computation. Model outputs are mapped to Banff scores using heuristic rules aligned with expert guidelines, and evaluated against expert-annotated ground truths. Our findings highlight both partial successes and critical failure modes, including structural omission, hallucination, and detection ambiguity. Even when final scores match expert annotations, inconsistencies in intermediate representations often undermine interpretability. These results reveal the limitations of current AI pipelines in replicating computational expert-level grading, and emphasize the importance of modular evaluation and computational Banff grading standard in guiding future model development for transplant pathology.

DyMorph-B2I: Dynamic and Morphology-Guided Binary-to-Instance Segmentation for Renal Pathology

Accurate morphological quantification of renal pathology functional units relies on instance-level segmentation, yet most existing datasets and automated methods provide only binary (semantic) masks, limiting the precision of downstream analyses. Although classical post-processing techniques such as watershed, morphological operations, and skeletonization, are often used to separate semantic masks into instances, their individual effectiveness is constrained by the diverse morphologies and complex connectivity found in renal tissue. In this study, we present DyMorph-B2I, a dynamic, morphology-guided binary-to-instance segmentation pipeline tailored for renal pathology. Our approach integrates watershed, skeletonization, and morphological operations within a unified framework, complemented by adaptive geometric refinement and customizable hyperparameter tuning for each class of functional unit. Through systematic parameter optimization, DyMorph-B2I robustly separates adherent and heterogeneous structures present in binary masks. Experimental results demonstrate that our method outperforms individual classical approaches and na\"ive combinations, enabling superior instance separation and facilitating more accurate morphometric analysis in renal pathology workflows. The pipeline is publicly available at: https://github.com/ddrrnn123/DyMorph-B2I.

Scale-up Unlearnable Examples Learning with High-Performance Computing

Recent advancements in AI models are structured to retain user interactions, which could inadvertently include sensitive healthcare data. In the healthcare field, particularly when radiologists use AI-driven diagnostic tools hosted on online platforms, there is a risk that medical imaging data may be repurposed for future AI training without explicit consent, spotlighting critical privacy and intellectual property concerns around healthcare data usage. Addressing these privacy challenges, a novel approach known as Unlearnable Examples (UEs) has been introduced, aiming to make data unlearnable to deep learning models. A prominent method within this area, called Unlearnable Clustering (UC), has shown improved UE performance with larger batch sizes but was previously limited by computational resources. To push the boundaries of UE performance with theoretically unlimited resources, we scaled up UC learning across various datasets using Distributed Data Parallel (DDP) training on the Summit supercomputer. Our goal was to examine UE efficacy at high-performance computing (HPC) levels to prevent unauthorized learning and enhance data security, particularly exploring the impact of batch size on UE's unlearnability. Utilizing the robust computational capabilities of the Summit, extensive experiments were conducted on diverse datasets such as Pets, MedMNist, Flowers, and Flowers102. Our findings reveal that both overly large and overly small batch sizes can lead to performance instability and affect accuracy. However, the relationship between batch size and unlearnability varied across datasets, highlighting the necessity for tailored batch size strategies to achieve optimal data protection. Our results underscore the critical role of selecting appropriate batch sizes based on the specific characteristics of each dataset to prevent learning and ensure data security in deep learning applications.

Persistence Image from 3D Medical Image: Superpixel and Optimized Gaussian Coefficient

Topological data analysis (TDA) uncovers crucial properties of objects in medical imaging. Methods based on persistent homology have demonstrated their advantages in capturing topological features that traditional deep learning methods cannot detect in both radiology and pathology. However, previous research primarily focused on 2D image analysis, neglecting the comprehensive 3D context. In this paper, we propose an innovative 3D TDA approach that incorporates the concept of superpixels to transform 3D medical image features into point cloud data. By Utilizing Optimized Gaussian Coefficient, the proposed 3D TDA method, for the first time, efficiently generate holistic Persistence Images for 3D volumetric data. Our 3D TDA method exhibits superior performance on the MedMNist3D dataset when compared to other traditional methods, showcasing its potential effectiveness in modeling 3D persistent homology-based topological analysis when it comes to classification tasks. The source code is publicly available at https://github.com/hrlblab/TopologicalDataAnalysis3D.