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The field of digital pathology has seen a proliferation of deep learning models in recent years. Despite substantial progress, it remains rare for other researchers and pathologists to be able to access models published in the literature and apply them to their own images. This is due to difficulties in both sharing and running models. To address these concerns, we introduce WSInfer: a new, open-source software ecosystem designed to make deep learning for pathology more streamlined and accessible. WSInfer comprises three main elements: 1) a Python package and command line tool to efficiently apply patch-based deep learning inference to whole slide images; 2) a QuPath extension that provides an alternative inference engine through user-friendly and interactive software, and 3) a model zoo, which enables pathology models and metadata to be easily shared in a standardized form. Together, these contributions aim to encourage wider reuse, exploration, and interrogation of deep learning models for research purposes, by putting them into the hands of pathologists and eliminating a need for coding experience when accessed through QuPath. The WSInfer source code is hosted on GitHub and documentation is available at https://wsinfer.readthedocs.io.

Halcyon is a new pathology imaging analysis and feature management system based on W3C linked-data open standards and is designed to scale to support the needs for the voluminous production of features from deep-learning feature pipelines. Halcyon can support multiple users with a web-based UX with access to all user data over a standards-based web API allowing for integration with other processes and software systems. Identity management and data security is also provided., Comment: 15 pages, 11 figures. arXiv admin note: text overlap with arXiv:2005.06469

Whole slide imaging (WSI) has become the primary modality for digital pathology data. However, due to the size and high-resolution nature of these images, they are generally only accessed in smaller sections or tiles via specialized platforms, most of which require extensive setup and/or costly infrastructure. These platforms typically also need a copy of the images to be locally available to them, potentially causing issues with data governance and provenance. To address these concerns, we developed ImageBox3, an in-browser tiling mechanism to enable zero-footprint traversal of remote WSI data. All computation is performed client-side without compromising user governance, operating public and private images alike as long as the storage service supports HTTP range requests (standard in Cloud storage and most web servers). ImageBox3 thus removes significant hurdles to WSI operation and effective collaboration, allowing for the sort of democratized analytical tools needed to establish participative, FAIR digital pathology data commons. Availability: code - https://github.com/episphere/imagebox3; fig1 (live) - https://episphere.github.io/imagebox3/demo/scriptTag ; fig2 (live) - https://episphere.github.io/imagebox3/demo/serviceWorker ; fig 3 (live) - https://observablehq.com/@prafulb/imagebox3-in-observable ., Comment: 9 pages, 3 figures

We evaluate the performance of federated learning (FL) in developing deep learning models for analysis of digitized tissue sections. A classification application was considered as the example use case, on quantifiying the distribution of tumor infiltrating lymphocytes within whole slide images (WSIs). A deep learning classification model was trained using 50*50 square micron patches extracted from the WSIs. We simulated a FL environment in which a dataset, generated from WSIs of cancer from numerous anatomical sites available by The Cancer Genome Atlas repository, is partitioned in 8 different nodes. Our results show that the model trained with the federated training approach achieves similar performance, both quantitatively and qualitatively, to that of a model trained with all the training data pooled at a centralized location. Our study shows that FL has tremendous potential for enabling development of more robust and accurate models for histopathology image analysis without having to collect large and diverse training data at a single location.

Regions of Interest (ROI) contain morphological features in pathology whole slide images (WSI) are delimited with polygons[1]. These polygons are often represented in either a textual notation (with the array of edges) or in a binary mask form. Textual notations have an advantage of human readability and portability, whereas, binary mask representations are more useful as the input and output of feature-extraction pipelines that employ deep learning methodologies. For any given whole slide image, more than a million cellular features can be segmented generating a corresponding number of polygons. The corpus of these segmentations for all processed whole slide images creates various challenges for filtering specific areas of data for use in interactive real-time and multi-scale displays and analysis. Simple range queries of image locations do not scale and, instead, spatial indexing schemes are required. In this paper we propose using Hilbert Curves simultaneously for spatial indexing and as a polygonal ROI representation. This is achieved by using a series of Hilbert Curves[2] creating an efficient and inherently spatially-indexed machine-usable form. The distinctive property of Hilbert curves that enables both mask and polygon delimitation of ROIs is that the elements of the vector extracted ro describe morphological features maintain their relative positions for different scales of the same image., Comment: 9 pages, 5 figures

Quantitative assessment of Tumor-TIL spatial relationships is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network (CNN) analysis pipelines to generate combined maps of cancer regions and tumor infiltrating lymphocytes (TILs) in routine diagnostic breast cancer whole slide tissue images (WSIs). We produce interactive whole slide maps that provide 1) insight about the structural patterns and spatial distribution of lymphocytic infiltrates and 2) facilitate improved quantification of TILs. We evaluated both tumor and TIL analyses using three CNN networks - Resnet-34, VGG16 and Inception v4, and demonstrated that the results compared favorably to those obtained by what believe are the best published methods. We have produced open-source tools and generated a public dataset consisting of tumor/TIL maps for 1,015 TCGA breast cancer images. We also present a customized web-based interface that enables easy visualization and interactive exploration of high-resolution combined Tumor-TIL maps for 1,015TCGA invasive breast cancer cases that can be downloaded for further downstream analyses., Comment: The American Journal of Pathology

We propose a software platform that integrates methods and tools for multi-objective parameter auto- tuning in tissue image segmentation workflows. The goal of our work is to provide an approach for improving the accuracy of nucleus/cell segmentation pipelines by tuning their input parameters. The shape, size and texture features of nuclei in tissue are important biomarkers for disease prognosis, and accurate computation of these features depends on accurate delineation of boundaries of nuclei. Input parameters in many nucleus segmentation workflows affect segmentation accuracy and have to be tuned for optimal performance. This is a time-consuming and computationally expensive process; automating this step facilitates more robust image segmentation workflows and enables more efficient application of image analysis in large image datasets. Our software platform adjusts the parameters of a nuclear segmentation algorithm to maximize the quality of image segmentation results while minimizing the execution time. It implements several optimization methods to search the parameter space efficiently. In addition, the methodology is developed to execute on high performance computing systems to reduce the execution time of the parameter tuning phase. Our results using three real-world image segmentation workflows demonstrate that the proposed solution is able to (1) search a small fraction (about 100 points) of the parameter space, which contains billions to trillions of points, and improve the quality of segmentation output by 1.20x, 1.29x, and 1.29x, on average; (2) decrease the execution time of a segmentation workflow by up to 11.79x while improving output quality; and (3) effectively use parallel systems to accelerate parameter tuning and segmentation phases., Comment: 29 pages, 5 figures