Abstract

Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis. Whole-slide imaging (WSI), i.e., the scanning and digitization of entire histology slides, are now being adopted across the world in pathology labs. Trained histopathologists can provide an accurate diagnosis of biopsy specimens based on WSI data. Given the dimensionality of WSIs and the increase in the number of potential cancer cases, analyzing these images is a time-consuming process. Automated segmentation of tumorous tissue helps in elevating the precision, speed, and reproducibility of research. In the recent past, deep learning-based techniques have provided state-of-the-art results in a wide variety of image analysis tasks, including the analysis of digitized slides. However, deep learning-based solutions pose many technical challenges, including the large size of WSI data, heterogeneity in images, and complexity of features. In this study, we propose a generalized deep learning-based framework for histopathology tissue analysis to address these challenges. Our framework is, in essence, a sequence of individual techniques in the preprocessing-training-inference pipeline which, in conjunction, improve the efficiency and the generalizability of the analysis. The combination of techniques we have introduced includes an ensemble segmentation model, division of the WSI into smaller overlapping patches while addressing class imbalances, efficient techniques for inference, and an efficient, patch-based uncertainty estimation framework. Our ensemble consists of DenseNet-121, Inception-ResNet-V2, and DeeplabV3Plus, where all the networks were trained end to end for every task. We demonstrate the efficacy and improved generalizability of our framework by evaluating it on a variety of histopathology tasks including breast cancer metastases (CAMELYON), colon cancer (DigestPath), and liver cancer (PAIP). Our proposed framework has state-of-the-art performance across all these tasks and is ranked within the top 5 currently for the challenges based on these datasets. The entire framework along with the trained models and the related documentation are made freely available at GitHub and PyPi. Our framework is expected to aid histopathologists in accurate and efficient initial diagnosis. Moreover, the estimated uncertainty maps will help clinicians to make informed decisions and further treatment planning or analysis.

Highlights

  • Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis

  • Ensemble segmentation model The ensemble comprises multiple fully convolutional architectures (FCN) architectures, each independently trained on different subsets of the training data

  • The problem of segmentation of gigapixel Whole-slide imaging (WSI) images was approached using the divide-and-conquer strategy by dividing the large image into computationally feasible patch sizes, running segmentation algorithms on the extracted patches, and stitching the individual outputs together to generate the segmentation of the entire WSI image

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Summary

Introduction

Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis. Deep learning-based techniques have provided state-of-the-art results in a wide variety of image analysis tasks, including the analysis of digitized slides. We propose a generalized deep learning-based framework for histopathology tissue analysis to address these challenges. A ­study[4] examining breast biopsies concordance among pathologists found that pathologists disagreed with each other on a diagnosis 24.7% of the time on average This high rate of misdiagnosis stresses the need to develop computer-aided methods to aid pathologists in histopathology. The increasing prevalence of WSI technology that can scan the entire tissue slide at the subcellular level makes the in-silico pathology analysis more v­ iable[6]. A typical glass-slide of size 20 mm × 15 mm results in gigapixel image of size 80,000 × 60,000 pixels

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