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.

Eosinophils Instance Object Segmentation on Whole Slide Imaging Using Multi-label Circle Representation

Eosinophilic esophagitis (EoE) is a chronic and relapsing disease characterized by esophageal inflammation. Symptoms of EoE include difficulty swallowing, food impaction, and chest pain which significantly impact the quality of life, resulting in nutritional impairments, social limitations, and psychological distress. The diagnosis of EoE is typically performed with a threshold (15 to 20) of eosinophils (Eos) per high-power field (HPF). Since the current counting process of Eos is a resource-intensive process for human pathologists, automatic methods are desired. Circle representation has been shown as a more precise, yet less complicated, representation for automatic instance cell segmentation such as CircleSnake approach. However, the CircleSnake was designed as a single-label model, which is not able to deal with multi-label scenarios. In this paper, we propose the multi-label CircleSnake model for instance segmentation on Eos. It extends the original CircleSnake model from a single-label design to a multi-label model, allowing segmentation of multiple object types. Experimental results illustrate the CircleSnake model's superiority over the traditional Mask R-CNN model and DeepSnake model in terms of average precision (AP) in identifying and segmenting eosinophils, thereby enabling enhanced characterization of EoE. This automated approach holds promise for streamlining the assessment process and improving diagnostic accuracy in EoE analysis. The source code has been made publicly available at https://github.com/yilinliu610730/EoE.

Deep Learning-Based Open Source Toolkit for Eosinophil Detection in Pediatric Eosinophilic Esophagitis

Eosinophilic Esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease, characterized by symptoms related to esophageal dysfunction and histological evidence of eosinophil-dominant inflammation. Owing to the intricate microscopic representation of EoE in imaging, current methodologies which depend on manual identification are not only labor-intensive but also prone to inaccuracies. In this study, we develop an open-source toolkit, named Open-EoE, to perform end-to-end whole slide image (WSI) level eosinophil (Eos) detection using one line of command via Docker. Specifically, the toolkit supports three state-of-the-art deep learning-based object detection models. Furthermore, Open-EoE further optimizes the performance by implementing an ensemble learning strategy, and enhancing the precision and reliability of our results. The experimental results demonstrated that the Open-EoE toolkit can efficiently detect Eos on a testing set with 289 WSIs. At the widely accepted threshold of >= 15 Eos per high power field (HPF) for diagnosing EoE, the Open-EoE achieved an accuracy of 91%, showing decent consistency with pathologist evaluations. This suggests a promising avenue for integrating machine learning methodologies into the diagnostic process for EoE. The docker and source code has been made publicly available at https://github.com/hrlblab/Open-EoE.