SynCLay: Interactive synthesis of histology images from bespoke cellular layouts.

Automated synthesis of histology images has several potential applications in computational pathology. However, no existing method can generate realistic tissue images with a bespoke cellular layout or user-defined histology parameters. In this work, we propose a novel framework called SynCLay (Synthesis from Cellular Layouts) that can construct realistic and high-quality histology images from user-defined cellular layouts along with annotated cellular boundaries. Tissue image generation based on bespoke cellular layouts through the proposed framework allows users to generate different histological patterns from arbitrary topological arrangement of different types of cells (e.g., neutrophils, lymphocytes, epithelial cells and others). SynCLay generated synthetic images can be helpful in studying the role of different types of cells present in the tumor microenvironment. Additionally, they can assist in balancing the distribution of cellular counts in tissue images for designing accurate cellular composition predictors by minimizing the effects of data imbalance. We train SynCLay in an adversarial manner and integrate a nuclear segmentation and classification model in its training to refine nuclear structures and generate nuclear masks in conjunction with synthetic images. During inference, we combine the model with another parametric model for generating colon images and associated cellular counts as annotations given the grade of differentiation and cellularities (cell densities) of different cells. We assess the generated images quantitatively using the Frechet Inception Distance and report on feedback from trained pathologists who assigned realism scores to a set of images generated by the framework. The average realism score across all pathologists for synthetic images was as high as that for the real images. Moreover, with the assistance from pathologists, we showcase the ability of the generated images to accurately differentiate between benign and malignant tumors, thus reinforcing their reliability. We demonstrate that the proposed framework can be used to add new cells to a tissue images and alter cellular positions. We also show that augmenting limited real data with the synthetic data generated by our framework can significantly boost prediction performance of the cellular composition prediction task. The implementation of the proposed SynCLay framework is available at https://github.com/Srijay/SynCLay-Framework.

TIAToolbox as an end-to-end library for advanced tissue image analytics.

Background: Computational pathology has seen rapid growth in recent years, driven by advanced deep-learning algorithms. Due to the sheer size and complexity of multi-gigapixel whole-slide images, to the best of our knowledge, there is no open-source software library providing a generic end-to-end API for pathology image analysis using best practices. Most researchers have designed custom pipelines from the bottom up, restricting the development of advanced algorithms to specialist users. To help overcome this bottleneck, we present TIAToolbox, a Python toolbox designed to make computational pathology accessible to computational, biomedical, and clinical researchers. Methods: By creating modular and configurable components, we enable the implementation of computational pathology algorithms in a way that is easy to use, flexible and extensible. We consider common sub-tasks including reading whole slide image data, patch extraction, stain normalization and augmentation, model inference, and visualization. For each of these steps, we provide a user-friendly application programming interface for commonly used methods and models. Results: We demonstrate the use of the interface to construct a full computational pathology deep-learning pipeline. We show, with the help of examples, how state-of-the-art deep-learning algorithms can be reimplemented in a streamlined manner using our library with minimal effort. Conclusions: We provide a usable and adaptable library with efficient, cutting-edge, and unit-tested tools for data loading, pre-processing, model inference, post-processing, and visualization. This enables a range of users to easily build upon recent deep-learning developments in the computational pathology literature.

SAFRON: Stitching Across the Frontier Network for Generating Colorectal Cancer Histology Images.

Automated synthesis of histology images has several potential applications including the development of data-efficient deep learning algorithms. In the field of computational pathology, where histology images are large in size and visual context is crucial, synthesis of large high-resolution images via generative modeling is an important but challenging task due to memory and computational constraints. To address this challenge, we propose a novel framework called SAFRON (Stitching Across the FROntier Network) to construct realistic, large high-resolution tissue images conditioned on input tissue component masks. The main novelty in the framework is integration of stitching in its loss function which enables generation of images of arbitrarily large sizes after training on relatively small image patches while preserving morphological features with minimal boundary artifacts. We have used the proposed framework for generating, to the best of our knowledge, the largest-sized synthetic histology images to date (up to 11K×8K pixels). Compared to existing approaches, our framework is efficient in terms of the memory required for training and computations needed for synthesizing large high-resolution images. The quality of generated images was assessed quantitatively using Frechet Inception Distance as well as by 7 trained pathologists, who assigned a realism score to a set of images generated by SAFRON. The average realism score across all pathologists for synthetic images was as high as that of real images. We also show that training with additional synthetic data generated by SAFRON can significantly boost prediction performance of gland segmentation and cancer detection algorithms in colorectal cancer histology images.