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Deep weakly-supervised learning methods for classification and localization in histology images: a survey.

TL;DR: Results indicate that several deep learning models, and in particular WILDCAT and deep MIL can provide a high level of classification accuracy, although pixel-wise localization of cancer regions remains an issue for such images.
Abstract: Using state-of-the-art deep learning models for cancer diagnosis presents several challenges related to the nature and availability of labeled histology images. In particular, cancer grading and localization in these images normally relies on both image- and pixel-level labels, the latter requiring a costly annotation process. In this survey, deep weakly-supervised learning (WSL) models are investigated to identify and locate diseases in histology images, without the need for pixel-level annotations. Given training data with global image-level labels, these models allow to simultaneously classify histology images and yield pixel-wise localization scores, thereby identifying the corresponding regions of interest (ROI). Since relevant WSL models have mainly been investigated within the computer vision community, and validated on natural scene images, we assess the extent to which they apply to histology images which have challenging properties, e.g. very large size, similarity between foreground/background, highly unstructured regions, stain heterogeneity, and noisy/ambiguous labels. The most relevant models for deep WSL are compared experimentally in terms of accuracy (classification and pixel-wise localization) on several public benchmark histology datasets for breast and colon cancer -- BACH ICIAR 2018, BreaKHis, CAMELYON16, and GlaS. Furthermore, for large-scale evaluation of WSL models on histology images, we propose a protocol to construct WSL datasets from Whole Slide Imaging. Results indicate that several deep learning models can provide a high level of classification accuracy, although accurate pixel-wise localization of cancer regions remains an issue for such images. Code is publicly available.
Citations
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Journal ArticleDOI
08 Jul 1992-JAMA
TL;DR: Several years ago, as editor-in-chief of the American Journal of Surgical Pathology, Dr Sternberg inaugurated a series of articles under the same heading as his book's title, Histology for Pathologists, which have now been considerably augmented and incorporated into this large, almost 1000-page, comprehensive text.
Abstract: Several years ago, as editor-in-chief of theAmerican Journal of Surgical Pathology, Dr Sternberg inaugurated a series of articles under the same heading as his book's title,Histology for Pathologists. These articles have now been considerably augmented and incorporated into this large, almost 1000-page, comprehensive text, whose 80 authors comprise an international cast of experts. Inevitably, the chapters vary in their quality, to an extent that reflects either inadequate editorial surveillance or adherence to a very tight deadline. I would assume that the instruction to contributors was to write on pure and applied histology, with the level of detail required by a practicing pathologist. As Dr Sternberg mentions in his preface, there are many histology books in existence, but none contains the detail and variations from normal that form a baseline for estimating the presence of disease. The papers originally published in theAmerican Journal of Surgical Pathologyare strictly

427 citations

Journal ArticleDOI
TL;DR: A comprehensive review of state-of-the-art deep learning approaches that have been used in the context of histopathological image analysis can be found in this paper, where a survey of over 130 papers is presented.

260 citations

01 Jan 2016
TL;DR: The fundamentals of light microscopy and electronic imaging can be found in this article, where the authors describe how people have looked hundreds of times for their favorite books like this fundamentals, but end up in harmful downloads, and instead they juggled with some infectious bugs inside their laptop.
Abstract: Thank you very much for reading fundamentals of light microscopy and electronic imaging. Maybe you have knowledge that, people have look hundreds times for their favorite books like this fundamentals of light microscopy and electronic imaging, but end up in harmful downloads. Rather than enjoying a good book with a cup of coffee in the afternoon, instead they juggled with some infectious bugs inside their laptop.

249 citations

Journal ArticleDOI
19 Oct 2021
TL;DR: In this article, a deep learning pipeline was developed to predict the status of key molecular pathways and mutations from whole-slide images of haematoxylin and eosin-stained colorectal cancer slides as an alternative to current tests.
Abstract: Summary Background Determining the status of molecular pathways and key mutations in colorectal cancer is crucial for optimal therapeutic decision making. We therefore aimed to develop a novel deep learning pipeline to predict the status of key molecular pathways and mutations from whole-slide images of haematoxylin and eosin-stained colorectal cancer slides as an alternative to current tests. Methods In this retrospective study, we used 502 diagnostic slides of primary colorectal tumours from 499 patients in The Cancer Genome Atlas colon and rectal cancer (TCGA-CRC-DX) cohort and developed a weakly supervised deep learning framework involving three separate convolutional neural network models. Whole-slide images were divided into equally sized tiles and model 1 (ResNet18) extracted tumour tiles from non-tumour tiles. These tumour tiles were inputted into model 2 (adapted ResNet34), trained by iterative draw and rank sampling to calculate a prediction score for each tile that represented the likelihood of a tile belonging to the molecular labels of high mutation density (vs low mutation density), microsatellite instability (vs microsatellite stability), chromosomal instability (vs genomic stability), CpG island methylator phenotype (CIMP)-high (vs CIMP-low), BRAFmut (vs BRAFWT), TP53mut (vs TP53WT), and KRASWT (vs KRASmut). These scores were used to identify the top-ranked titles from each slide, and model 3 (HoVer-Net) segmented and classified the different types of cell nuclei in these tiles. We calculated the area under the convex hull of the receiver operating characteristic curve (AUROC) as a model performance measure and compared our results with those of previously published methods. Findings Our iterative draw and rank sampling method yielded mean AUROCs for the prediction of hypermutation (0·81 [SD 0·03] vs 0·71), microsatellite instability (0·86 [0·04] vs 0·74), chromosomal instability (0·83 [0·02] vs 0·73), BRAFmut (0·79 [0·01] vs 0·66), and TP53mut (0·73 [0·02] vs 0·64) in the TCGA-CRC-DX cohort that were higher than those from previously published methods, and an AUROC for KRASmut that was similar to previously reported methods (0·60 [SD 0·04] vs 0·60). Mean AUROC for predicting CIMP-high status was 0·79 (SD 0·05). We found high proportions of tumour-infiltrating lymphocytes and necrotic tumour cells to be associated with microsatellite instability, and high proportions of tumour-infiltrating lymphocytes and a low proportion of necrotic tumour cells to be associated with hypermutation. Interpretation After large-scale validation, our proposed algorithm for predicting clinically important mutations and molecular pathways, such as microsatellite instability, in colorectal cancer could be used to stratify patients for targeted therapies with potentially lower costs and quicker turnaround times than sequencing-based or immunohistochemistry-based approaches. Funding The UK Medical Research Council.

101 citations

Journal ArticleDOI
TL;DR: The result of the review process indicated that deep learning methods have achieved state-of-the-art in tumor detection, segmentation, feature extraction and classification.
Abstract: Deep learning algorithms have become the first choice as an approach to medical image analysis, face recognition, and emotion recognition. In this survey, several deep-learning-based approaches applied to breast cancer, cervical cancer, brain tumor, colon and lung cancers are studied and reviewed. Deep learning has been applied in almost all of the imaging modalities used for cervical and breast cancers and MRIs for the brain tumor. The result of the review process indicated that deep learning methods have achieved state-of-the-art in tumor detection, segmentation, feature extraction and classification. As presented in this paper, the deep learning approaches were used in three different modes that include training from scratch, transfer learning through freezing some layers of the deep learning network and modifying the architecture to reduce the number of parameters existing in the network. Moreover, the application of deep learning to imaging devices for the detection of various cancer cases has been studied by researchers affiliated to academic and medical institutes in economically developed countries; while, the study has not had much attention in Africa despite the dramatic soar of cancer risks in the continent.

45 citations


Cites background from "Deep weakly-supervised learning met..."

  • ...The advancement of whole slide imaging (WSI) scanners has opened new opportunities in automating pathology image analysis by digitizing the slides [115]....

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References
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Proceedings ArticleDOI
27 Jun 2016
TL;DR: In this article, the authors proposed a residual learning framework to ease the training of networks that are substantially deeper than those used previously, which won the 1st place on the ILSVRC 2015 classification task.
Abstract: Deeper neural networks are more difficult to train. We present a residual learning framework to ease the training of networks that are substantially deeper than those used previously. We explicitly reformulate the layers as learning residual functions with reference to the layer inputs, instead of learning unreferenced functions. We provide comprehensive empirical evidence showing that these residual networks are easier to optimize, and can gain accuracy from considerably increased depth. On the ImageNet dataset we evaluate residual nets with a depth of up to 152 layers—8× deeper than VGG nets [40] but still having lower complexity. An ensemble of these residual nets achieves 3.57% error on the ImageNet test set. This result won the 1st place on the ILSVRC 2015 classification task. We also present analysis on CIFAR-10 with 100 and 1000 layers. The depth of representations is of central importance for many visual recognition tasks. Solely due to our extremely deep representations, we obtain a 28% relative improvement on the COCO object detection dataset. Deep residual nets are foundations of our submissions to ILSVRC & COCO 2015 competitions1, where we also won the 1st places on the tasks of ImageNet detection, ImageNet localization, COCO detection, and COCO segmentation.

123,388 citations

Proceedings Article
03 Dec 2012
TL;DR: The state-of-the-art performance of CNNs was achieved by Deep Convolutional Neural Networks (DCNNs) as discussed by the authors, which consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax.
Abstract: We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0% which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overriding in the fully-connected layers we employed a recently-developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.

73,978 citations

Proceedings ArticleDOI
Jia Deng1, Wei Dong1, Richard Socher1, Li-Jia Li1, Kai Li1, Li Fei-Fei1 
20 Jun 2009
TL;DR: A new database called “ImageNet” is introduced, a large-scale ontology of images built upon the backbone of the WordNet structure, much larger in scale and diversity and much more accurate than the current image datasets.
Abstract: The explosion of image data on the Internet has the potential to foster more sophisticated and robust models and algorithms to index, retrieve, organize and interact with images and multimedia data. But exactly how such data can be harnessed and organized remains a critical problem. We introduce here a new database called “ImageNet”, a large-scale ontology of images built upon the backbone of the WordNet structure. ImageNet aims to populate the majority of the 80,000 synsets of WordNet with an average of 500-1000 clean and full resolution images. This will result in tens of millions of annotated images organized by the semantic hierarchy of WordNet. This paper offers a detailed analysis of ImageNet in its current state: 12 subtrees with 5247 synsets and 3.2 million images in total. We show that ImageNet is much larger in scale and diversity and much more accurate than the current image datasets. Constructing such a large-scale database is a challenging task. We describe the data collection scheme with Amazon Mechanical Turk. Lastly, we illustrate the usefulness of ImageNet through three simple applications in object recognition, image classification and automatic object clustering. We hope that the scale, accuracy, diversity and hierarchical structure of ImageNet can offer unparalleled opportunities to researchers in the computer vision community and beyond.

49,639 citations


"Deep weakly-supervised learning met..." refers methods in this paper

  • ...For all methods, we use an ImageNet-pretrained ResNet-18 (He et al., 2016) architecture as a feature extractor....

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  • ...Most of these techniques have been originally proposed to process natural images and validated on well-known public benchmarks such as ImageNet (Deng et al., 2009), e....

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  • ...Most of these techniques have been originally proposed to process natural scene images and validated on well-known public benchmarks such as ImageNet (Deng et al., 2009), Pascal VOC (Everingham et al., 2010) and MS-COCO (Lin et al., 2014)....

    [...]

Book ChapterDOI
05 Oct 2015
TL;DR: Neber et al. as discussed by the authors proposed a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently, which can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks.
Abstract: There is large consent that successful training of deep networks requires many thousand annotated training samples. In this paper, we present a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently. The architecture consists of a contracting path to capture context and a symmetric expanding path that enables precise localization. We show that such a network can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks. Using the same network trained on transmitted light microscopy images (phase contrast and DIC) we won the ISBI cell tracking challenge 2015 in these categories by a large margin. Moreover, the network is fast. Segmentation of a 512x512 image takes less than a second on a recent GPU. The full implementation (based on Caffe) and the trained networks are available at http://lmb.informatik.uni-freiburg.de/people/ronneber/u-net .

49,590 citations

Book
18 Nov 2016
TL;DR: Deep learning as mentioned in this paper is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts, and it is used in many applications such as natural language processing, speech recognition, computer vision, online recommendation systems, bioinformatics, and videogames.
Abstract: Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. Because the computer gathers knowledge from experience, there is no need for a human computer operator to formally specify all the knowledge that the computer needs. The hierarchy of concepts allows the computer to learn complicated concepts by building them out of simpler ones; a graph of these hierarchies would be many layers deep. This book introduces a broad range of topics in deep learning. The text offers mathematical and conceptual background, covering relevant concepts in linear algebra, probability theory and information theory, numerical computation, and machine learning. It describes deep learning techniques used by practitioners in industry, including deep feedforward networks, regularization, optimization algorithms, convolutional networks, sequence modeling, and practical methodology; and it surveys such applications as natural language processing, speech recognition, computer vision, online recommendation systems, bioinformatics, and videogames. Finally, the book offers research perspectives, covering such theoretical topics as linear factor models, autoencoders, representation learning, structured probabilistic models, Monte Carlo methods, the partition function, approximate inference, and deep generative models. Deep Learning can be used by undergraduate or graduate students planning careers in either industry or research, and by software engineers who want to begin using deep learning in their products or platforms. A website offers supplementary material for both readers and instructors.

38,208 citations