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.

Multi-Modality Conditioned Variational U-Net for Field-of-View Extension in Brain Diffusion MRI

An incomplete field-of-view (FOV) in diffusion magnetic resonance imaging (dMRI) can severely hinder the volumetric and bundle analyses of whole-brain white matter connectivity. Although existing works have investigated imputing the missing regions using deep generative models, it remains unclear how to specifically utilize additional information from paired multi-modality data and whether this can enhance the imputation quality and be useful for downstream tractography. To fill this gap, we propose a novel framework for imputing dMRI scans in the incomplete part of the FOV by integrating the learned diffusion features in the acquired part of the FOV to the complete brain anatomical structure. We hypothesize that by this design the proposed framework can enhance the imputation performance of the dMRI scans and therefore be useful for repairing whole-brain tractography in corrupted dMRI scans with incomplete FOV. We tested our framework on two cohorts from different sites with a total of 96 subjects and compared it with a baseline imputation method that treats the information from T1w and dMRI scans equally. The proposed framework achieved significant improvements in imputation performance, as demonstrated by angular correlation coefficient (p < 1E-5), and in downstream tractography accuracy, as demonstrated by Dice score (p < 0.01). Results suggest that the proposed framework improved imputation performance in dMRI scans by specifically utilizing additional information from paired multi-modality data, compared with the baseline method. The imputation achieved by the proposed framework enhances whole brain tractography, and therefore reduces the uncertainty when analyzing bundles associated with neurodegenerative.

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.

Dataset Distillation in Medical Imaging: A Feasibility Study

Data sharing in the medical image analysis field has potential yet remains underappreciated. The aim is often to share datasets efficiently with other sites to train models effectively. One possible solution is to avoid transferring the entire dataset while still achieving similar model performance. Recent progress in data distillation within computer science offers promising prospects for sharing medical data efficiently without significantly compromising model effectiveness. However, it remains uncertain whether these methods would be applicable to medical imaging, since medical and natural images are distinct fields. Moreover, it is intriguing to consider what level of performance could be achieved with these methods. To answer these questions, we conduct investigations on a variety of leading data distillation methods, in different contexts of medical imaging. We evaluate the feasibility of these methods with extensive experiments in two aspects: 1) Assess the impact of data distillation across multiple datasets characterized by minor or great variations. 2) Explore the indicator to predict the distillation performance. Our extensive experiments across multiple medical datasets reveal that data distillation can significantly reduce dataset size while maintaining comparable model performance to that achieved with the full dataset, suggesting that a small, representative sample of images can serve as a reliable indicator of distillation success. This study demonstrates that data distillation is a viable method for efficient and secure medical data sharing, with the potential to facilitate enhanced collaborative research and clinical applications.

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.

HoloHisto: End-to-end Gigapixel WSI Segmentation with 4K Resolution Sequential Tokenization

In digital pathology, the traditional method for deep learning-based image segmentation typically involves a two-stage process: initially segmenting high-resolution whole slide images (WSI) into smaller patches (e.g., 256x256, 512x512, 1024x1024) and subsequently reconstructing them to their original scale. This method often struggles to capture the complex details and vast scope of WSIs. In this paper, we propose the holistic histopathology (HoloHisto) segmentation method to achieve end-to-end segmentation on gigapixel WSIs, whose maximum resolution is above 80,000$\times$70,000 pixels. HoloHisto fundamentally shifts the paradigm of WSI segmentation to an end-to-end learning fashion with 1) a large (4K) resolution base patch for elevated visual information inclusion and efficient processing, and 2) a novel sequential tokenization mechanism to properly model the contextual relationships and efficiently model the rich information from the 4K input. To our best knowledge, HoloHisto presents the first holistic approach for gigapixel resolution WSI segmentation, supporting direct I/O of complete WSI and their corresponding gigapixel masks. Under the HoloHisto platform, we unveil a random 4K sampler that transcends ultra-high resolution, delivering 31 and 10 times more pixels than standard 2D and 3D patches, respectively, for advancing computational capabilities. To facilitate efficient 4K resolution dense prediction, we leverage sequential tokenization, utilizing a pre-trained image tokenizer to group image features into a discrete token grid. To assess the performance, our team curated a new kidney pathology image segmentation (KPIs) dataset with WSI-level glomeruli segmentation from whole mouse kidneys. From the results, HoloHisto-4K delivers remarkable performance gains over previous state-of-the-art models.

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.