Deep learning for digital pathology

Demir, Çiğdem Gündüz
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Bilkent University
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Histopathological examination is today’s gold standard for cancer diagnosis and grading. However, this task is time consuming and prone to errors as it requires detailed visual inspection and interpretation of a histopathological sample provided on a glass slide under a microscope by an expert pathologist. Low-cost and high-technology whole slide digital scanners produced in recent years have eliminated the disadvantages of physical glass slide samples by digitizing histopathological samples and relocating them to digital media. Digital pathology aims at alleviating the problems of traditional examination approaches by providing auxiliary computerized tools that quantitatively analyze digitized histopathological images. Traditional machine learning methods have proposed to extract handcrafted features from histopathological images and to use these features in the design of a classification or a segmentation algorithm. The performance of these methods mainly relies on the features that they use, and thus, their success strictly depends on the ability of these features to successfully quantify the histopathology domain. More recent studies have employed deep architectures to learn expressive and robust features directly from images avoiding complex feature extraction procedures of traditional approaches. Although deep learning methods perform well in many classification and segmentation problems, convolutional neural networks that they frequently make use of require annotated data for training and this makes it difficult to utilize unannotated data that cover the majority of the available data in the histopathology domain. This thesis addresses the challenges of traditional and deep learning approaches by incorporating unsupervised learning into classification and segmentation algorithms for feature extraction and training regularization purposes in the histopathology domain. As the first contribution of this thesis, the first study presents a new unsupervised feature extractor for effective representation and classification of histopathological tissue images. This study introduces a deep belief network to quantize the salient subregions, which are identified with domain-specific prior knowledge, by extracting a set of features directly learned on image data in an unsupervised way and uses the distribution of these quantizations for image representation and classification. As its second contribution, the second study proposes a new regularization method to train a fully convolutional network for semantic tissue segmentation in histopathological images. This study relies on the benefit of unsupervised learning, in the form of image reconstruction, for network training. To this end, it puts forward an idea of defining a new embedding, which is generated by superimposing an input image on its segmentation map, that allows uniting the main supervised task of semantic segmentation and an auxiliary unsupervised task of image reconstruction into a single one and proposes to learn this united task by a generative adversarial network. We compare our classification and segmentation methods with traditional machine learning methods and the state-of-the-art deep learning algorithms on various histopathological image datasets. Visual and quantitative results of our experiments demonstrate that the proposed methods are capable of learning robust features from histopathological images and provides more accurate results than their counterparts.

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Deep learning, Feature learning, Training regularization, Image embedding, Generative adversarial networks, Semantic segmentation, Digital pathology, Automated cancer diagnosis, Histopathological image analysis
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