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.

mTREE: Multi-Level Text-Guided Representation End-to-End Learning for Whole Slide Image Analysis

Multi-modal learning adeptly integrates visual and textual data, but its application to histopathology image and text analysis remains challenging, particularly with large, high-resolution images like gigapixel Whole Slide Images (WSIs). Current methods typically rely on manual region labeling or multi-stage learning to assemble local representations (e.g., patch-level) into global features (e.g., slide-level). However, there is no effective way to integrate multi-scale image representations with text data in a seamless end-to-end process. In this study, we introduce Multi-Level Text-Guided Representation End-to-End Learning (mTREE). This novel text-guided approach effectively captures multi-scale WSI representations by utilizing information from accompanying textual pathology information. mTREE innovatively combines - the localization of key areas (global-to-local) and the development of a WSI-level image-text representation (local-to-global) - into a unified, end-to-end learning framework. In this model, textual information serves a dual purpose: firstly, functioning as an attention map to accurately identify key areas, and secondly, acting as a conduit for integrating textual features into the comprehensive representation of the image. Our study demonstrates the effectiveness of mTREE through quantitative analyses in two image-related tasks: classification and survival prediction, showcasing its remarkable superiority over baselines.

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.

Nucleus subtype classification using inter-modality learning

Understanding the way cells communicate, co-locate, and interrelate is essential to understanding human physiology. Hematoxylin and eosin (H&E) staining is ubiquitously available both for clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge has recently innovated on robust artificial intelligence labeling of six cell types on H&E stains of the colon. However, this is a very small fraction of the number of potential cell classification types. Specifically, the CoNIC Challenge is unable to classify epithelial subtypes (progenitor, endocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), or connective subtypes (fibroblasts, stromal). In this paper, we propose to use inter-modality learning to label previously un-labelable cell types on virtual H&E. We leveraged multiplexed immunofluorescence (MxIF) histology imaging to identify 14 subclasses of cell types. We performed style transfer to synthesize virtual H&E from MxIF and transferred the higher density labels from MxIF to these virtual H&E images. We then evaluated the efficacy of learning in this approach. We identified helper T and progenitor nuclei with positive predictive values of $0.34 \pm 0.15$ (prevalence $0.03 \pm 0.01$) and $0.47 \pm 0.1$ (prevalence $0.07 \pm 0.02$) respectively on virtual H&E. This approach represents a promising step towards automating annotation in digital pathology.

Evaluation Kidney Layer Segmentation on Whole Slide Imaging using Convolutional Neural Networks and Transformers

The segmentation of kidney layer structures, including cortex, outer stripe, inner stripe, and inner medulla within human kidney whole slide images (WSI) plays an essential role in automated image analysis in renal pathology. However, the current manual segmentation process proves labor-intensive and infeasible for handling the extensive digital pathology images encountered at a large scale. In response, the realm of digital renal pathology has seen the emergence of deep learning-based methodologies. However, very few, if any, deep learning based approaches have been applied to kidney layer structure segmentation. Addressing this gap, this paper assesses the feasibility of performing deep learning based approaches on kidney layer structure segmetnation. This study employs the representative convolutional neural network (CNN) and Transformer segmentation approaches, including Swin-Unet, Medical-Transformer, TransUNet, U-Net, PSPNet, and DeepLabv3+. We quantitatively evaluated six prevalent deep learning models on renal cortex layer segmentation using mice kidney WSIs. The empirical results stemming from our approach exhibit compelling advancements, as evidenced by a decent Mean Intersection over Union (mIoU) index. The results demonstrate that Transformer models generally outperform CNN-based models. By enabling a quantitative evaluation of renal cortical structures, deep learning approaches are promising to empower these medical professionals to make more informed kidney layer segmentation.