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Register a new userDeep Learning Assessment of Tumor Proliferation in Breast Cancer Histological Images
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Dayong Wang
Publication date
2016
fields
Informatics Engineering
and research's language is
English
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Current analysis of tumor proliferation, the most salient prognostic biomarker for invasive breast cancer, is limited to subjective mitosis counting by pathologists in localized regions of tissue images. This study presents the first data-driven integrative approach to characterize the severity of tumor growth and spread on a categorical and molecular level, utilizing multiple biologically salient deep learning classifiers to develop a comprehensive prognostic model. Our approach achieves pathologist-level performance on three-class categorical tumor severity prediction. It additionally pioneers prediction of molecular expression data from a tissue image, obtaining a Spearmans rank correlation coefficient of 0.60 with ex vivo mean calculated RNA expression. Furthermore, our framework is applied to identify over two hundred unprecedented biomarkers critical to the accurate assessment of tumor proliferation, validating our proposed integrative pipeline as the first to holistically and objectively analyze histopathological images.
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Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is highly subjective and labor-intensive task. Previous efforts to automate tumor proliferation assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohens kappa score of $kappa$ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearmans correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labelled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task.
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.
Breast cancer is one of the leading causes of mortality in women. Early detection and treatment are imperative for improving survival rates, which have steadily increased in recent years as a result of more sophisticated computer-aided-diagnosis (CAD) systems. A critical component of breast cancer diagnosis relies on histopathology, a laborious and highly subjective process. Consequently, CAD systems are essential to reduce inter-rater variability and supplement the analyses conducted by specialists. In this paper, a transfer-learning based approach is proposed, for the task of breast histology image classification into four tissue sub-types, namely, normal, benign, textit{in situ} carcinoma and invasive carcinoma. The histology images, provided as part of the BACH 2018 grand challenge, were first normalized to correct for color variations resulting from inconsistencies during slide preparation. Subsequently, image patches were extracted and used to fine-tune Google`s Inception-V3 and ResNet50 convolutional neural networks (CNNs), both pre-trained on the ImageNet database, enabling them to learn domain-specific features, necessary to classify the histology images. The ResNet50 network (based on residual learning) achieved a test classification accuracy of 97.50% for four classes, outperforming the Inception-V3 network which achieved an accuracy of 91.25%.
Breast cancer is one of the leading fatal disease worldwide with high risk control if early discovered. Conventional method for breast screening is x-ray mammography, which is known to be challenging for early detection of cancer lesions. The dense breast structure produced due to the compression process during imaging lead to difficulties to recognize small size abnormalities. Also, inter- and intra-variations of breast tissues lead to significant difficulties to achieve high diagnosis accuracy using hand-crafted features. Deep learning is an emerging machine learning technology that requires a relatively high computation power. Yet, it proved to be very effective in several difficult tasks that requires decision making at the level of human intelligence. In this paper, we develop a new network architecture inspired by the U-net structure that can be used for effective and early detection of breast cancer. Results indicate a high rate of sensitivity and specificity that indicate potential usefulness of the proposed approach in clinical use.
Purpose: To determine whether deep learning models can distinguish between breast cancer molecular subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and methods: In this institutional review board-approved single-center study, we analyzed DCE-MR images of 270 patients at our institution. Lesions of interest were identified by radiologists. The task was to automatically determine whether the tumor is of the Luminal A subtype or of another subtype based on the MR image patches representing the tumor. Three different deep learning approaches were used to classify the tumor according to their molecular subtypes: learning from scratch where only tumor patches were used for training, transfer learning where networks pre-trained on natural images were fine-tuned using tumor patches, and off-the-shelf deep features where the features extracted by neural networks trained on natural images were used for classification with a support vector machine. Network architectures utilized in our experiments were GoogleNet, VGG, and CIFAR. We used 10-fold crossvalidation method for validation and area under the receiver operating characteristic (AUC) as the measure of performance. Results: The best AUC performance for distinguishing molecular subtypes was 0.65 (95% CI:[0.57,0.71]) and was achieved by the off-the-shelf deep features approach. The highest AUC performance for training from scratch was 0.58 (95% CI:[0.51,0.64]) and the best AUC performance for transfer learning was 0.60 (95% CI:[0.52,0.65]) respectively. For the off-the-shelf approach, the features extracted from the fully connected layer performed the best. Conclusion: Deep learning may play a role in discovering radiogenomic associations in breast cancer.
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