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.
Podocytes, specialized epithelial cells that envelop the glomerular capillaries, play a pivotal role in maintaining renal health. The current description and quantification of features on pathology slides are limited, prompting the need for innovative solutions to comprehensively assess diverse phenotypic attributes within Whole Slide Images (WSIs). In particular, understanding the morphological characteristics of podocytes, terminally differentiated glomerular epithelial cells, is crucial for studying glomerular injury. This paper introduces the Spatial Pathomics Toolkit (SPT) and applies it to podocyte pathomics. The SPT consists of three main components: (1) instance object segmentation, enabling precise identification of podocyte nuclei; (2) pathomics feature generation, extracting a comprehensive array of quantitative features from the identified nuclei; and (3) robust statistical analyses, facilitating a comprehensive exploration of spatial relationships between morphological and spatial transcriptomics features.The SPT successfully extracted and analyzed morphological and textural features from podocyte nuclei, revealing a multitude of podocyte morphomic features through statistical analysis. Additionally, we demonstrated the SPT's ability to unravel spatial information inherent to podocyte distribution, shedding light on spatial patterns associated with glomerular injury. By disseminating the SPT, our goal is to provide the research community with a powerful and user-friendly resource that advances cellular spatial pathomics in renal pathology. The implementation and its complete source code of the toolkit are made openly accessible at https://github.com/hrlblab/spatial_pathomics.
The Segment Anything Model (SAM) is a recently proposed prompt-based segmentation model in a generic zero-shot segmentation approach. With the zero-shot segmentation capacity, SAM achieved impressive flexibility and precision on various segmentation tasks. However, the current pipeline requires manual prompts during the inference stage, which is still resource intensive for biomedical image segmentation. In this paper, instead of using prompts during the inference stage, we introduce a pipeline that utilizes the SAM, called all-in-SAM, through the entire AI development workflow (from annotation generation to model finetuning) without requiring manual prompts during the inference stage. Specifically, SAM is first employed to generate pixel-level annotations from weak prompts (e.g., points, bounding box). Then, the pixel-level annotations are used to finetune the SAM segmentation model rather than training from scratch. Our experimental results reveal two key findings: 1) the proposed pipeline surpasses the state-of-the-art (SOTA) methods in a nuclei segmentation task on the public Monuseg dataset, and 2) the utilization of weak and few annotations for SAM finetuning achieves competitive performance compared to using strong pixel-wise annotated data.
Diffusion-weighted magnetic resonance imaging (DW-MRI) is a critical imaging method for capturing and modeling tissue microarchitecture at a millimeter scale. A common practice to model the measured DW-MRI signal is via fiber orientation distribution function (fODF). This function is the essential first step for the downstream tractography and connectivity analyses. With recent advantages in data sharing, large-scale multi-site DW-MRI datasets are being made available for multi-site studies. However, measurement variabilities (e.g., inter- and intra-site variability, hardware performance, and sequence design) are inevitable during the acquisition of DW-MRI. Most existing model-based methods (e.g., constrained spherical deconvolution (CSD)) and learning based methods (e.g., deep learning (DL)) do not explicitly consider such variabilities in fODF modeling, which consequently leads to inferior performance on multi-site and/or longitudinal diffusion studies. In this paper, we propose a novel data-driven deep constrained spherical deconvolution method to explicitly constrain the scan-rescan variabilities for a more reproducible and robust estimation of brain microstructure from repeated DW-MRI scans. Specifically, the proposed method introduces a new 3D volumetric scanner-invariant regularization scheme during the fODF estimation. We study the Human Connectome Project (HCP) young adults test-retest group as well as the MASiVar dataset (with inter- and intra-site scan/rescan data). The Baltimore Longitudinal Study of Aging (BLSA) dataset is employed for external validation. From the experimental results, the proposed data-driven framework outperforms the existing benchmarks in repeated fODF estimation. The proposed method is assessing the downstream connectivity analysis and shows increased performance in distinguishing subjects with different biomarkers.
The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various segmentation prompts (e.g., points, boxes, masks). It makes the SAM attractive for medical image analysis, especially for digital pathology where the training data are rare. In this study, we evaluate the zero-shot segmentation performance of SAM model on representative segmentation tasks on whole slide imaging (WSI), including (1) tumor segmentation, (2) non-tumor tissue segmentation, (3) cell nuclei segmentation. Core Results: The results suggest that the zero-shot SAM model achieves remarkable segmentation performance for large connected objects. However, it does not consistently achieve satisfying performance for dense instance object segmentation, even with 20 prompts (clicks/boxes) on each image. We also summarized the identified limitations for digital pathology: (1) image resolution, (2) multiple scales, (3) prompt selection, and (4) model fine-tuning. In the future, the few-shot fine-tuning with images from downstream pathological segmentation tasks might help the model to achieve better performance in dense object segmentation.
Diffusion-weighted (DW) MRI measures the direction and scale of the local diffusion process in every voxel through its spectrum in q-space, typically acquired in one or more shells. Recent developments in micro-structure imaging and multi-tissue decomposition have sparked renewed attention to the radial b-value dependence of the signal. Applications in tissue classification and micro-architecture estimation, therefore, require a signal representation that extends over the radial as well as angular domain. Multiple approaches have been proposed that can model the non-linear relationship between the DW-MRI signal and biological microstructure. In the past few years, many deep learning-based methods have been developed towards faster inference speed and higher inter-scan consistency compared with traditional model-based methods (e.g., multi-shell multi-tissue constrained spherical deconvolution). However, a multi-stage learning strategy is typically required since the learning process relied on various middle representations, such as simple harmonic oscillator reconstruction (SHORE) representation. In this work, we present a unified dynamic network with a single-stage spherical convolutional neural network, which allows efficient fiber orientation distribution function (fODF) estimation through heterogeneous multi-shell diffusion MRI sequences. We study the Human Connectome Project (HCP) young adults with test-retest scans. From the experimental results, the proposed single-stage method outperforms prior multi-stage approaches in repeated fODF estimation with shell dropoff and single-shell DW-MRI sequences.
With the rapid development of self-supervised learning (e.g., contrastive learning), the importance of having large-scale images (even without annotations) for training a more generalizable AI model has been widely recognized in medical image analysis. However, collecting large-scale task-specific unannotated data at scale can be challenging for individual labs. Existing online resources, such as digital books, publications, and search engines, provide a new resource for obtaining large-scale images. However, published images in healthcare (e.g., radiology and pathology) consist of a considerable amount of compound figures with subplots. In order to extract and separate compound figures into usable individual images for downstream learning, we propose a simple compound figure separation (SimCFS) framework without using the traditionally required detection bounding box annotations, with a new loss function and a hard case simulation. Our technical contribution is four-fold: (1) we introduce a simulation-based training framework that minimizes the need for resource extensive bounding box annotations; (2) we propose a new side loss that is optimized for compound figure separation; (3) we propose an intra-class image augmentation method to simulate hard cases; and (4) to the best of our knowledge, this is the first study that evaluates the efficacy of leveraging self-supervised learning with compound image separation. From the results, the proposed SimCFS achieved state-of-the-art performance on the ImageCLEF 2016 Compound Figure Separation Database. The pretrained self-supervised learning model using large-scale mined figures improved the accuracy of downstream image classification tasks with a contrastive learning algorithm. The source code of SimCFS is made publicly available at https://github.com/hrlblab/ImageSeperation.
Comprehensive semantic segmentation on renal pathological images is challenging due to the heterogeneous scales of the objects. For example, on a whole slide image (WSI), the cross-sectional areas of glomeruli can be 64 times larger than that of the peritubular capillaries, making it impractical to segment both objects on the same patch, at the same scale. To handle this scaling issue, prior studies have typically trained multiple segmentation networks in order to match the optimal pixel resolution of heterogeneous tissue types. This multi-network solution is resource-intensive and fails to model the spatial relationship between tissue types. In this paper, we propose the Omni-Seg+ network, a scale-aware dynamic neural network that achieves multi-object (six tissue types) and multi-scale (5X to 40X scale) pathological image segmentation via a single neural network. The contribution of this paper is three-fold: (1) a novel scale-aware controller is proposed to generalize the dynamic neural network from single-scale to multi-scale; (2) semi-supervised consistency regularization of pseudo-labels is introduced to model the inter-scale correlation of unannotated tissue types into a single end-to-end learning paradigm; and (3) superior scale-aware generalization is evidenced by directly applying a model trained on human kidney images to mouse kidney images, without retraining. By learning from ~150,000 human pathological image patches from six tissue types at three different resolutions, our approach achieved superior segmentation performance according to human visual assessment and evaluation of image-omics (i.e., spatial transcriptomics). The official implementation is available at https://github.com/ddrrnn123/Omni-Seg.
The quantitative detection, segmentation, and characterization of glomeruli from high-resolution whole slide imaging (WSI) play essential roles in the computer-assisted diagnosis and scientific research in digital renal pathology. Historically, such comprehensive quantification requires extensive programming skills in order to be able to handle heterogeneous and customized computational tools. To bridge the gap of performing glomerular quantification for non-technical users, we develop the Glo-In-One toolkit to achieve holistic glomerular detection, segmentation, and characterization via a single line of command. Additionally, we release a large-scale collection of 30,000 unlabeled glomerular images to further facilitate the algorithmic development of self-supervised deep learning. The inputs of the Glo-In-One toolkit are WSIs, while the outputs are (1) WSI-level multi-class circle glomerular detection results (which can be directly manipulated with ImageScope), (2) glomerular image patches with segmentation masks, and (3) different lesion types. To leverage the performance of the Glo-In-One toolkit, we introduce self-supervised deep learning to glomerular quantification via large-scale web image mining. The GGS fine-grained classification model achieved a decent performance compared with baseline supervised methods while only using 10% of the annotated data. The glomerular detection achieved an average precision of 0.627 with circle representations, while the glomerular segmentation achieved a 0.955 patch-wise Dice Similarity Coefficient (DSC).
Recent studies have demonstrated the diagnostic and prognostic values of global glomerulosclerosis (GGS) in IgA nephropathy, aging, and end-stage renal disease. However, the fine-grained quantitative analysis of multiple GGS subtypes (e.g., obsolescent, solidified, and disappearing glomerulosclerosis) is typically a resource extensive manual process. Very few automatic methods, if any, have been developed to bridge this gap for such analytics. In this paper, we present a holistic pipeline to quantify GGS (with both detection and classification) from a whole slide image in a fully automatic manner. In addition, we conduct the fine-grained classification for the sub-types of GGS. Our study releases the open-source quantitative analytical tool for fine-grained GGS characterization while tackling the technical challenges in unbalanced classification and integrating detection and classification.