ASIGN: An Anatomy-aware Spatial Imputation Graphic Network for 3D Spatial Transcriptomics

Spatial transcriptomics (ST) is an emerging technology that enables medical computer vision scientists to automatically interpret the molecular profiles underlying morphological features. Currently, however, most deep learning-based ST analyses are limited to two-dimensional (2D) sections, which can introduce diagnostic errors due to the heterogeneity of pathological tissues across 3D sections. Expanding ST to three-dimensional (3D) volumes is challenging due to the prohibitive costs; a 2D ST acquisition already costs over 50 times more than whole slide imaging (WSI), and a full 3D volume with 10 sections can be an order of magnitude more expensive. To reduce costs, scientists have attempted to predict ST data directly from WSI without performing actual ST acquisition. However, these methods typically yield unsatisfying results. To address this, we introduce a novel problem setting: 3D ST imputation using 3D WSI histology sections combined with a single 2D ST slide. To do so, we present the Anatomy-aware Spatial Imputation Graph Network (ASIGN) for more precise, yet affordable, 3D ST modeling. The ASIGN architecture extends existing 2D spatial relationships into 3D by leveraging cross-layer overlap and similarity-based expansion. Moreover, a multi-level spatial attention graph network integrates features comprehensively across different data sources. We evaluated ASIGN on three public spatial transcriptomics datasets, with experimental results demonstrating that ASIGN achieves state-of-the-art performance on both 2D and 3D scenarios. Code is available at https://github.com/hrlblab/ASIGN.

GloFinder: AI-empowered QuPath Plugin for WSI-level Glomerular Detection, Visualization, and Curation

Artificial intelligence (AI) has demonstrated significant success in automating the detection of glomeruli, the key functional units of the kidney, from whole slide images (WSIs) in kidney pathology. However, existing open-source tools are often distributed as source code or Docker containers, requiring advanced programming skills that hinder accessibility for non-programmers, such as clinicians. Additionally, current models are typically trained on a single dataset and lack flexibility in adjusting confidence levels for predictions. To overcome these challenges, we introduce GloFinder, a QuPath plugin designed for single-click automated glomeruli detection across entire WSIs with online editing through the graphical user interface (GUI). GloFinder employs CircleNet, an anchor-free detection framework utilizing circle representations for precise object localization, with models trained on approximately 160,000 manually annotated glomeruli. To further enhance accuracy, the plugin incorporates Weighted Circle Fusion (WCF), an ensemble method that combines confidence scores from multiple CircleNet models to produce refined predictions, achieving superior performance in glomerular detection. GloFinder enables direct visualization and editing of results in QuPath, facilitating seamless interaction for clinicians and providing a powerful tool for nephropathology research and clinical practice.

Cross-organ Deployment of EOS Detection AI without Retraining: Feasibility and Limitation

Chronic rhinosinusitis (CRS) is characterized by persistent inflammation in the paranasal sinuses, leading to typical symptoms of nasal congestion, facial pressure, olfactory dysfunction, and discolored nasal drainage, which can significantly impact quality-of-life. Eosinophils (Eos), a crucial component in the mucosal immune response, have been linked to disease severity in CRS. The diagnosis of eosinophilic CRS typically uses a threshold of 10-20 eos per high-power field (HPF). However, manually counting Eos in histological samples is laborious and time-intensive, making the use of AI-driven methods for automated evaluations highly desirable. Interestingly, eosinophils are predominantly located in the gastrointestinal (GI) tract, which has prompted the release of numerous deep learning models trained on GI data. This study leverages a CircleSnake model initially trained on upper-GI data to segment Eos cells in whole slide images (WSIs) of nasal tissues. It aims to determine the extent to which Eos segmentation models developed for the GI tract can be adapted to nasal applications without retraining. The experimental results show promising accuracy in some WSIs, although, unsurprisingly, the performance varies across cases. This paper details these performance outcomes, delves into the reasons for such variations, and aims to provide insights that could guide future development of deep learning models for eosinophilic CRS.

How Good Are We? Evaluating Cell AI Foundation Models in Kidney Pathology with Human-in-the-Loop Enrichment

Training AI foundation models has emerged as a promising large-scale learning approach for addressing real-world healthcare challenges, including digital pathology. While many of these models have been developed for tasks like disease diagnosis and tissue quantification using extensive and diverse training datasets, their readiness for deployment on some arguably simplest tasks, such as nuclei segmentation within a single organ (e.g., the kidney), remains uncertain. This paper seeks to answer this key question, "How good are we?", by thoroughly evaluating the performance of recent cell foundation models on a curated multi-center, multi-disease, and multi-species external testing dataset. Additionally, we tackle a more challenging question, "How can we improve?", by developing and assessing human-in-the-loop data enrichment strategies aimed at enhancing model performance while minimizing the reliance on pixel-level human annotation. To address the first question, we curated a multicenter, multidisease, and multispecies dataset consisting of 2,542 kidney whole slide images (WSIs). Three state-of-the-art (SOTA) cell foundation models-Cellpose, StarDist, and CellViT-were selected for evaluation. To tackle the second question, we explored data enrichment algorithms by distilling predictions from the different foundation models with a human-in-the-loop framework, aiming to further enhance foundation model performance with minimal human efforts. Our experimental results showed that all three foundation models improved over their baselines with model fine-tuning with enriched data. Interestingly, the baseline model with the highest F1 score does not yield the best segmentation outcomes after fine-tuning. This study establishes a benchmark for the development and deployment of cell vision foundation models tailored for real-world data applications.

Automatic Image Unfolding and Stitching Framework for Esophageal Lining Video Based on Density-Weighted Feature Matching

Endoscopy is a crucial tool for diagnosing the gastrointestinal tract, but its effectiveness is often limited by a narrow field of view and the dynamic nature of the internal environment, especially in the esophagus, where complex and repetitive patterns make image stitching challenging. This paper introduces a novel automatic image unfolding and stitching framework tailored for esophageal videos captured during endoscopy. The method combines feature matching algorithms, including LoFTR, SIFT, and ORB, to create a feature filtering pool and employs a Density-Weighted Homography Optimization (DWHO) algorithm to enhance stitching accuracy. By merging consecutive frames, the framework generates a detailed panoramic view of the esophagus, enabling thorough and accurate visual analysis. Experimental results show the framework achieves low Root Mean Square Error (RMSE) and high Structural Similarity Index (SSIM) across extensive video sequences, demonstrating its potential for clinical use and improving the quality and continuity of endoscopic visual data.

Assessment of Cell Nuclei AI Foundation Models in Kidney Pathology

Cell nuclei instance segmentation is a crucial task in digital kidney pathology. Traditional automatic segmentation methods often lack generalizability when applied to unseen datasets. Recently, the success of foundation models (FMs) has provided a more generalizable solution, potentially enabling the segmentation of any cell type. In this study, we perform a large-scale evaluation of three widely used state-of-the-art (SOTA) cell nuclei foundation models (Cellpose, StarDist, and CellViT). Specifically, we created a highly diverse evaluation dataset consisting of 2,542 kidney whole slide images (WSIs) collected from both human and rodent sources, encompassing various tissue types, sizes, and staining methods. To our knowledge, this is the largest-scale evaluation of its kind to date. Our quantitative analysis of the prediction distribution reveals a persistent performance gap in kidney pathology. Among the evaluated models, CellViT demonstrated superior performance in segmenting nuclei in kidney pathology. However, none of the foundation models are perfect; a performance gap remains in general nuclei segmentation for kidney pathology.

HATs: Hierarchical Adaptive Taxonomy Segmentation for Panoramic Pathology Image Analysis

Panoramic image segmentation in computational pathology presents a remarkable challenge due to the morphologically complex and variably scaled anatomy. For instance, the intricate organization in kidney pathology spans multiple layers, from regions like the cortex and medulla to functional units such as glomeruli, tubules, and vessels, down to various cell types. In this paper, we propose a novel Hierarchical Adaptive Taxonomy Segmentation (HATs) method, which is designed to thoroughly segment panoramic views of kidney structures by leveraging detailed anatomical insights. Our approach entails (1) the innovative HATs technique which translates spatial relationships among 15 distinct object classes into a versatile "plug-and-play" loss function that spans across regions, functional units, and cells, (2) the incorporation of anatomical hierarchies and scale considerations into a unified simple matrix representation for all panoramic entities, (3) the adoption of the latest AI foundation model (EfficientSAM) as a feature extraction tool to boost the model's adaptability, yet eliminating the need for manual prompt generation in conventional segment anything model (SAM). Experimental findings demonstrate that the HATs method offers an efficient and effective strategy for integrating clinical insights and imaging precedents into a unified segmentation model across more than 15 categories. The official implementation is publicly available at https://github.com/hrlblab/HATs.

Weighted Circle Fusion: Ensembling Circle Representation from Different Object Detection Results

Recently, the use of circle representation has emerged as a method to improve the identification of spherical objects (such as glomeruli, cells, and nuclei) in medical imaging studies. In traditional bounding box-based object detection, combining results from multiple models improves accuracy, especially when real-time processing isn't crucial. Unfortunately, this widely adopted strategy is not readily available for combining circle representations. In this paper, we propose Weighted Circle Fusion (WCF), a simple approach for merging predictions from various circle detection models. Our method leverages confidence scores associated with each proposed bounding circle to generate averaged circles. Our method undergoes thorough evaluation on a proprietary dataset for glomerular detection in object detection within whole slide imaging (WSI). The findings reveal a performance gain of 5 %, respectively, compared to existing ensemble methods. Furthermore, the Weighted Circle Fusion technique not only improves the precision of object detection in medical images but also notably decreases false detections, presenting a promising direction for future research and application in pathological image analysis.

Circle Representation for Medical Instance Object Segmentation

Recently, circle representation has been introduced for medical imaging, designed specifically to enhance the detection of instance objects that are spherically shaped (e.g., cells, glomeruli, and nuclei). Given its outstanding effectiveness in instance detection, it is compelling to consider the application of circle representation for segmenting instance medical objects. In this study, we introduce CircleSnake, a simple end-to-end segmentation approach that utilizes circle contour deformation for segmenting ball-shaped medical objects at the instance level. The innovation of CircleSnake lies in these three areas: (1) It substitutes the complex bounding box-to-octagon contour transformation with a more consistent and rotation-invariant bounding circle-to-circle contour adaptation. This adaptation specifically targets ball-shaped medical objects. (2) The circle representation employed in CircleSnake significantly reduces the degrees of freedom to two, compared to eight in the octagon representation. This reduction enhances both the robustness of the segmentation performance and the rotational consistency of the method. (3) CircleSnake is the first end-to-end deep instance segmentation pipeline to incorporate circle representation, encompassing consistent circle detection, circle contour proposal, and circular convolution in a unified framework. This integration is achieved through the novel application of circular graph convolution within the context of circle detection and instance segmentation. In practical applications, such as the detection of glomeruli, nuclei, and eosinophils in pathological images, CircleSnake has demonstrated superior performance and greater rotation invariance when compared to benchmarks. The code has been made publicly available: https://github.com/hrlblab/CircleSnake.

PrPSeg: Universal Proposition Learning for Panoramic Renal Pathology Segmentation

Understanding the anatomy of renal pathology is crucial for advancing disease diagnostics, treatment evaluation, and clinical research. The complex kidney system comprises various components across multiple levels, including regions (cortex, medulla), functional units (glomeruli, tubules), and cells (podocytes, mesangial cells in glomerulus). Prior studies have predominantly overlooked the intricate spatial interrelations among objects from clinical knowledge. In this research, we introduce a novel universal proposition learning approach, called panoramic renal pathology segmentation (PrPSeg), designed to segment comprehensively panoramic structures within kidney by integrating extensive knowledge of kidney anatomy. In this paper, we propose (1) the design of a comprehensive universal proposition matrix for renal pathology, facilitating the incorporation of classification and spatial relationships into the segmentation process; (2) a token-based dynamic head single network architecture, with the improvement of the partial label image segmentation and capability for future data enlargement; and (3) an anatomy loss function, quantifying the inter-object relationships across the kidney.