Histopathological examination is today's gold standard for cancer diagnosis. However, this task is time consuming and prone to errors as it requires a detailed visual inspection and interpretation of a pathologist. Digital pathology aims at alleviating these problems by providing computerized methods that quantitatively analyze digitized histopathological tissue images. The performance of these methods mainly rely on features that they use, and thus, their success strictly depends on the ability of these features successfully quantifying the histopathology domain. With this motivation, this paper presents a new unsupervised feature extractor for effective representation and classification of histopathological tissue images. This feature extractor has three main contributions: First, it proposes to identify salient subregions in an image, based on domain-specific prior knowledge, and to quantify the image by employing only the characteristics of these subregions instead of considering the characteristics of all image locations. Second, it introduces a new deep learning based technique that quantizes the salient subregions by extracting a set of features directly learned on image data and uses the distribution of these quantizations for image representation and classification. To this end, the proposed deep learning based technique constructs a deep belief network of restricted Boltzmann machines (RBMs), defines the activation values of the hidden unit nodes in the final RBM as the features, and learns the quantizations by clustering these features in an unsupervised way. Third, this extractor is the first example of successfully using restricted Boltzmann machines in the domain of histopathological image analysis. Our experiments on microscopic colon tissue images reveal that the proposed feature extractor is effective to obtain more accurate classification results compared to its counterparts.

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