PySpatial: A High-Speed Whole Slide Image Pathomics Toolkit

Whole Slide Image (WSI) analysis plays a crucial role in modern digital pathology, enabling large-scale feature extraction from tissue samples. However, traditional feature extraction pipelines based on tools like CellProfiler often involve lengthy workflows, requiring WSI segmentation into patches, feature extraction at the patch level, and subsequent mapping back to the original WSI. To address these challenges, we present PySpatial, a high-speed pathomics toolkit specifically designed for WSI-level analysis. PySpatial streamlines the conventional pipeline by directly operating on computational regions of interest, reducing redundant processing steps. Utilizing rtree-based spatial indexing and matrix-based computation, PySpatial efficiently maps and processes computational regions, significantly accelerating feature extraction while maintaining high accuracy. Our experiments on two datasets-Perivascular Epithelioid Cell (PEC) and data from the Kidney Precision Medicine Project (KPMP)-demonstrate substantial performance improvements. For smaller and sparse objects in PEC datasets, PySpatial achieves nearly a 10-fold speedup compared to standard CellProfiler pipelines. For larger objects, such as glomeruli and arteries in KPMP datasets, PySpatial achieves a 2-fold speedup. These results highlight PySpatial's potential to handle large-scale WSI analysis with enhanced efficiency and accuracy, paving the way for broader applications in digital pathology.

Efficient MedSAMs: Segment Anything in Medical Images on Laptop

Promptable segmentation foundation models have emerged as a transformative approach to addressing the diverse needs in medical images, but most existing models require expensive computing, posing a big barrier to their adoption in clinical practice. In this work, we organized the first international competition dedicated to promptable medical image segmentation, featuring a large-scale dataset spanning nine common imaging modalities from over 20 different institutions. The top teams developed lightweight segmentation foundation models and implemented an efficient inference pipeline that substantially reduced computational requirements while maintaining state-of-the-art segmentation accuracy. Moreover, the post-challenge phase advanced the algorithms through the design of performance booster and reproducibility tasks, resulting in improved algorithms and validated reproducibility of the winning solution. Furthermore, the best-performing algorithms have been incorporated into the open-source software with a user-friendly interface to facilitate clinical adoption. The data and code are publicly available to foster the further development of medical image segmentation foundation models and pave the way for impactful real-world applications.

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.

Glo-In-One-v2: Holistic Identification of Glomerular Cells, Tissues, and Lesions in Human and Mouse Histopathology

Segmenting glomerular intraglomerular tissue and lesions traditionally depends on detailed morphological evaluations by expert nephropathologists, a labor-intensive process susceptible to interobserver variability. Our group previously developed the Glo-In-One toolkit for integrated detection and segmentation of glomeruli. In this study, we leverage the Glo-In-One toolkit to version 2 with fine-grained segmentation capabilities, curating 14 distinct labels for tissue regions, cells, and lesions across a dataset of 23,529 annotated glomeruli across human and mouse histopathology data. To our knowledge, this dataset is among the largest of its kind to date.In this study, we present a single dynamic head deep learning architecture designed to segment 14 classes within partially labeled images of human and mouse pathology data. Our model was trained using a training set derived from 368 annotated kidney whole-slide images (WSIs) to identify 5 key intraglomerular tissues covering Bowman's capsule, glomerular tuft, mesangium, mesangial cells, and podocytes. Additionally, the network segments 9 glomerular lesion classes including adhesion, capsular drop, global sclerosis, hyalinosis, mesangial lysis, microaneurysm, nodular sclerosis, mesangial expansion, and segmental sclerosis. The glomerulus segmentation model achieved a decent performance compared with baselines, and achieved a 76.5 % average Dice Similarity Coefficient (DSC). Additional, transfer learning from rodent to human for glomerular lesion segmentation model has enhanced the average segmentation accuracy across different types of lesions by more than 3 %, as measured by Dice scores. The Glo-In-One-v2 model and trained weight have been made publicly available at https: //github.com/hrlblab/Glo-In-One_v2.

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.

Cross-Species Data Integration for Enhanced Layer Segmentation in Kidney Pathology

Accurate delineation of the boundaries between the renal cortex and medulla is crucial for subsequent functional structural analysis and disease diagnosis. Training high-quality deep-learning models for layer segmentation relies on the availability of large amounts of annotated data. However, due to the patient's privacy of medical data and scarce clinical cases, constructing pathological datasets from clinical sources is relatively difficult and expensive. Moreover, using external natural image datasets introduces noise during the domain generalization process. Cross-species homologous data, such as mouse kidney data, which exhibits high structural and feature similarity to human kidneys, has the potential to enhance model performance on human datasets. In this study, we incorporated the collected private Periodic Acid-Schiff (PAS) stained mouse kidney dataset into the human kidney dataset for joint training. The results showed that after introducing cross-species homologous data, the semantic segmentation models based on CNN and Transformer architectures achieved an average increase of 1.77% and 1.24% in mIoU, and 1.76% and 0.89% in Dice score for the human renal cortex and medulla datasets, respectively. This approach is also capable of enhancing the model's generalization ability. This indicates that cross-species homologous data, as a low-noise trainable data source, can help improve model performance under conditions of limited clinical samples. Code is available at https://github.com/hrlblab/layer_segmentation.

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.

Adapting Mouse Pathological Model to Human Glomerular Lesion Segmentation

Moving from animal models to human applications in preclinical research encompasses a broad spectrum of disciplines in medical science. A fundamental element in the development of new drugs, treatments, diagnostic methods, and in deepening our understanding of disease processes is the accurate measurement of kidney tissues. Past studies have demonstrated the viability of translating glomeruli segmentation techniques from mouse models to human applications. Yet, these investigations tend to neglect the complexities involved in segmenting pathological glomeruli affected by different lesions. Such lesions present a wider range of morphological variations compared to healthy glomerular tissue, which are arguably more valuable than normal glomeruli in clinical practice. Furthermore, data on lesions from animal models can be more readily scaled up from disease models and whole kidney biopsies. This brings up a question: ``\textit{Can a pathological segmentation model trained on mouse models be effectively applied to human patients?}" To answer this question, we introduced GLAM, a deep learning study for fine-grained segmentation of human kidney lesions using a mouse model, addressing mouse-to-human transfer learning, by evaluating different learning strategies for segmenting human pathological lesions using zero-shot transfer learning and hybrid learning by leveraging mouse samples. From the results, the hybrid learning model achieved superior performance.

PFPs: Prompt-guided Flexible Pathological Segmentation for Diverse Potential Outcomes Using Large Vision and Language Models

The Vision Foundation Model has recently gained attention in medical image analysis. Its zero-shot learning capabilities accelerate AI deployment and enhance the generalizability of clinical applications. However, segmenting pathological images presents a special focus on the flexibility of segmentation targets. For instance, a single click on a Whole Slide Image (WSI) could signify a cell, a functional unit, or layers, adding layers of complexity to the segmentation tasks. Current models primarily predict potential outcomes but lack the flexibility needed for physician input. In this paper, we explore the potential of enhancing segmentation model flexibility by introducing various task prompts through a Large Language Model (LLM) alongside traditional task tokens. Our contribution is in four-fold: (1) we construct a computational-efficient pipeline that uses finetuned language prompts to guide flexible multi-class segmentation; (2) We compare segmentation performance with fixed prompts against free-text; (3) We design a multi-task kidney pathology segmentation dataset and the corresponding various free-text prompts; and (4) We evaluate our approach on the kidney pathology dataset, assessing its capacity to new cases during inference.