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Register a new userSparse Autoencoder for Unsupervised Nucleus Detection and Representation in Histopathology Images
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Added by
Le Hou
Publication date
2017
fields
Informatics Engineering
and research's language is
English
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Histopathology images are crucial to the study of complex diseases such as cancer. The histologic characteristics of nuclei play a key role in disease diagnosis, prognosis and analysis. In this work, we propose a sparse Convolutional Autoencoder (CAE) for fully unsupervised, simultaneous nucleus detection and feature extraction in histopathology tissue images. Our CAE detects and encodes nuclei in image patches in tissue images into sparse feature maps that encode both the location and appearance of nuclei. Our CAE is the first unsupervised detection network for computer vision applications. The pretrained nucleus detection and feature extraction modules in our CAE can be fine-tuned for supervised learning in an end-to-end fashion. We evaluate our method on four datasets and reduce the errors of state-of-the-art methods up to 42%. We are able to achieve comparable performance with only 5% of the fully-supervised annotation cost.
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The proliferative activity of breast tumors, which is routinely estimated by counting of mitotic figures in hematoxylin and eosin stained histology sections, is considered to be one of the most important prognostic markers. However, mitosis counting is laborious, subjective and may suffer from low inter-observer agreement. With the wider acceptance of whole slide images in pathology labs, automatic image analysis has been proposed as a potential solution for these issues. In this paper, the results from the Assessment of Mitosis Detection Algorithms 2013 (AMIDA13) challenge are described. The challenge was based on a data set consisting of 12 training and 11 testing subjects, with more than one thousand annotated mitotic figures by multiple observers. Short descriptions and results from the evaluation of eleven methods are presented. The top performing method has an error rate that is comparable to the inter-observer agreement among pathologists.
Cell detection in histopathology images is of great value in clinical practice. textit{Convolutional neural networks} (CNNs) have been applied to cell detection to improve the detection accuracy, where cell annotations are required for network training. However, due to the variety and large number of cells, complete annotations that include every cell of interest in the training images can be challenging. Usually, incomplete annotations can be achieved, where positive labeling results are carefully examined to ensure their reliability but there can be other positive instances, i.e., cells of interest, that are not included in the annotations. This annotation strategy leads to a lack of knowledge about true negative samples. Most existing methods simply treat instances that are not labeled as positive as truly negative during network training, which can adversely affect the network performance. In this work, to address the problem of incomplete annotations, we formulate the training of detection networks as a positive-unlabeled learning problem. Specifically, the classification loss in network training is revised to take into account incomplete annotations, where the terms corresponding to negative samples are approximated with the true positive samples and the other samples of which the labels are unknown. To evaluate the proposed method, experiments were performed on a publicly available dataset for mitosis detection in breast cancer cells, and the experimental results show that our method improves the performance of cell detection given incomplete annotations for training.
Local discriminative representation is needed in many medical image analysis tasks such as identifying sub-types of lesion or segmenting detailed components of anatomical structures. However, the commonly applied supervised representation learning methods require a large amount of annotated data, and unsupervised discriminative representation learning distinguishes different images by learning a global feature, both of which are not suitable for localized medical image analysis tasks. In order to avoid the limitations of these two methods, we introduce local discrimination into unsupervised representation learning in this work. The model contains two branches: one is an embedding branch which learns an embedding function to disperse dissimilar pixels over a low-dimensional hypersphere; and the other is a clustering branch which learns a clustering function to classify similar pixels into the same cluster. These two branches are trained simultaneously in a mutually beneficial pattern, and the learnt local discriminative representations are able to well measure the similarity of local image regions. These representations can be transferred to enhance various downstream tasks. Meanwhile, they can also be applied to cluster anatomical structures from unlabeled medical images under the guidance of topological priors from simulation or other structures with similar topological characteristics. The effectiveness and usefulness of the proposed method are demonstrated by enhancing various downstream tasks and clustering anatomical structures in retinal images and chest X-ray images.
Hematoxylin and Eosin stained histopathology image analysis is essential for the diagnosis and study of complicated diseases such as cancer. Existing state-of-the-art approaches demand extensive amount of supervised training data from trained pathologists. In this work we synthesize in an unsupervised manner, large histopathology image datasets, suitable for supervised training tasks. We propose a unified pipeline that: a) generates a set of initial synthetic histopathology images with paired information about the nuclei such as segmentation masks; b) refines the initial synthetic images through a Generative Adversarial Network (GAN) to reference styles; c) trains a task-specific CNN and boosts the performance of the task-specific CNN with on-the-fly generated adversarial examples. Our main contribution is that the synthetic images are not only realistic, but also representative (in reference styles) and relatively challenging for training task-specific CNNs. We test our method for nucleus segmentation using images from four cancer types. When no supervised data exists for a cancer type, our method without supervision cost significantly outperforms supervised methods which perform across-cancer generalization. Even when supervised data exists for all cancer types, our approach without supervision cost performs better than supervised methods.
Registration networks have shown great application potentials in medical image analysis. However, supervised training methods have a great demand for large and high-quality labeled datasets, which is time-consuming and sometimes impractical due to data sharing issues. Unsupervised image registration algorithms commonly employ intensity-based similarity measures as loss functions without any manual annotations. These methods estimate the parameterized transformations between pairs of moving and fixed images through the optimization of the network parameters during training. However, these methods become less effective when the image quality varies, e.g., some images are corrupted by substantial noise or artifacts. In this work, we propose a novel approach based on a low-rank representation, i.e., Regnet-LRR, to tackle the problem. We project noisy images into a noise-free low-rank space, and then compute the similarity between the images. Based on the low-rank similarity measure, we train the registration network to predict the dense deformation fields of noisy image pairs. We highlight that the low-rank projection is reformulated in a way that the registration network can successfully update gradients. With two tasks, i.e., cardiac and abdominal intra-modality registration, we demonstrate that the low-rank representation can boost the generalization ability and robustness of models as well as bring significant improvements in noisy data registration scenarios.
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