No Arabic abstract
In this paper, we propose a novel method for highly efficient follicular segmentation of thyroid cytopathological WSIs. Firstly, we propose a hybrid segmentation architecture, which integrates a classifier into Deeplab V3 by adding a branch. A large amount of the WSI segmentation time is saved by skipping the irrelevant areas using the classification branch. Secondly, we merge the low scale fine features into the original atrous spatial pyramid pooling (ASPP) in Deeplab V3 to accurately represent the details in cytopathological images. Thirdly, our hybrid model is trained by a criterion-oriented adaptive loss function, which leads the model converging much faster. Experimental results on a collection of thyroid patches demonstrate that the proposed model reaches 80.9% on the segmentation accuracy. Besides, 93% time is reduced for the WSI segmentation by using our proposed method, and the WSI-level accuracy achieves 53.4%.
Weak supervision learning on classification labels has demonstrated high performance in various tasks. When a few pixel-level fine annotations are also affordable, it is natural to leverage both of the pixel-level (e.g., segmentation) and image level (e.g., classification) annotation to further improve the performance. In computational pathology, however, such weak or mixed supervision learning is still a challenging task, since the high resolution of whole slide images makes it unattainable to perform end-to-end training of classification models. An alternative approach is to analyze such data by patch-base model training, i.e., using self-supervised learning to generate pixel-level pseudo labels for patches. However, such methods usually have model drifting issues, i.e., hard to converge, because the noise accumulates during the self-training process. To handle those problems, we propose a mixed supervision learning framework for super high-resolution images to effectively utilize their various labels (e.g., sufficient image-level coarse annotations and a few pixel-level fine labels). During the patch training stage, this framework can make use of coarse image-level labels to refine self-supervised learning and generate high-quality pixel-level pseudo labels. A comprehensive strategy is proposed to suppress pixel-level false positives and false negatives. Three real-world datasets with very large number of images (i.e., more than 10,000 whole slide images) and various types of labels are used to evaluate the effectiveness of mixed supervision learning. We reduced the false positive rate by around one third compared to state of the art while retaining 100% sensitivity, in the task of image-level classification.
While challenging, the dense segmentation of histology images is a necessary first step to assess changes in tissue architecture and cellular morphology. Although specific convolutional neural network architectures have been applied with great success to the problem, few effectively incorporate visual context information from multiple scales. With this paper, we present a systematic comparison of different architectures to assess how including multi-scale information affects segmentation performance. A publicly available breast cancer and a locally collected prostate cancer datasets are being utilised for this study. The results support our hypothesis that visual context and scale play a crucial role in histology image classification problems.
Convolutional neural networks, the state of the art for image segmentation, have been successfully applied to histology images by many computational researchers. However, the translatability of this technology to clinicians and biological researchers is limited due to the complex and undeveloped user interface of the code, as well as the extensive computer setup required. As an extension of our previous work (arXiv:1812.07509), we have developed a tool for segmentation of whole slide images (WSIs) with an easy to use graphical user interface. Our tool runs a state-of-the-art convolutional neural network for segmentation of WSIs in the cloud. Our plugin is built on the open source tool HistomicsTK by Kitware Inc. (Clifton Park, NY), which provides remote data management and viewing abilities for WSI datasets. The ability to access this tool over the internet will facilitate widespread use by computational non-experts. Users can easily upload slides to a server where our plugin is installed and perform human in the loop segmentation analysis remotely. This tool is open source, and has the ability to be adapted to segment of any pathological structure. For a proof of concept, we have trained it to segment glomeruli from renal tissue images, achieving an F-score > 0.97 on holdout tissue slides.
Consecutive thin sections of tissue samples make it possible to study local variation in e.g. protein expression and tumor heterogeneity by staining for a new protein in each section. In order to compare and correlate patterns of different proteins, the images have to be registered with high accuracy. The problem we want to solve is registration of gigapixel whole slide images (WSI). This presents 3 challenges: (i) Images are very large; (ii) Thin sections result in artifacts that make global affine registration prone to very large local errors; (iii) Local affine registration is required to preserve correct tissue morphology (local size, shape and texture). In our approach we compare WSI registration based on automatic and manual feature selection on either the full image or natural sub-regions (as opposed to square tiles). Working with natural sub-regions, in an interactive tool makes it possible to exclude regions containing scientifically irrelevant information. We also present a new way to visualize local registration quality by a Registration Confidence Map (RCM). With this method, intra-tumor heterogeneity and charateristics of the tumor microenvironment can be observed and quantified.
Convolutional Neural Networks (CNN) are state-of-the-art models for many image classification tasks. However, to recognize cancer subtypes automatically, training a CNN on gigapixel resolution Whole Slide Tissue Images (WSI) is currently computationally impossible. The differentiation of cancer subtypes is based on cellular-level visual features observed on image patch scale. Therefore, we argue that in this situation, training a patch-level classifier on image patches will perform better than or similar to an image-level classifier. The challenge becomes how to intelligently combine patch-level classification results and model the fact that not all patches will be discriminative. We propose to train a decision fusion model to aggregate patch-level predictions given by patch-level CNNs, which to the best of our knowledge has not been shown before. Furthermore, we formulate a novel Expectation-Maximization (EM) based method that automatically locates discriminative patches robustly by utilizing the spatial relationships of patches. We apply our method to the classification of glioma and non-small-cell lung carcinoma cases into subtypes. The classification accuracy of our method is similar to the inter-observer agreement between pathologists. Although it is impossible to train CNNs on WSIs, we experimentally demonstrate using a comparable non-cancer dataset of smaller images that a patch-based CNN can outperform an image-based CNN.