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Deep Learning for Identifying Metastatic Breast Cancer

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 Added by Andrew Beck
 Publication date 2016
and research's language is English




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The International Symposium on Biomedical Imaging (ISBI) held a grand challenge to evaluate computational systems for the automated detection of metastatic breast cancer in whole slide images of sentinel lymph node biopsies. Our team won both competitions in the grand challenge, obtaining an area under the receiver operating curve (AUC) of 0.925 for the task of whole slide image classification and a score of 0.7051 for the tumor localization task. A pathologist independently reviewed the same images, obtaining a whole slide image classification AUC of 0.966 and a tumor localization score of 0.733. Combining our deep learning systems predictions with the human pathologists diagnoses increased the pathologists AUC to 0.995, representing an approximately 85 percent reduction in human error rate. These results demonstrate the power of using deep learning to produce significant improvements in the accuracy of pathological diagnoses.



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Objectives: Most cancer data sources lack information on metastatic recurrence. Electronic medical records (EMRs) and population-based cancer registries contain complementary information on cancer treatment and outcomes, yet are rarely used synergistically. To enable detection of metastatic breast cancer (MBC), we applied a semi-supervised machine learning framework to linked EMR-California Cancer Registry (CCR) data. Materials and Methods: We studied 11,459 female patients treated at Stanford Health Care who received an incident breast cancer diagnosis from 2000-2014. The dataset consisted of structured data and unstructured free-text clinical notes from EMR, linked to CCR, a component of the Surveillance, Epidemiology and End Results (SEER) database. We extracted information on metastatic disease from patient notes to infer a class label and then trained a regularized logistic regression model for MBC classification. We evaluated model performance on a gold standard set of set of 146 patients. Results: There are 495 patients with de novo stage IV MBC, 1,374 patients initially diagnosed with Stage 0-III disease had recurrent MBC, and 9,590 had no evidence of metastatis. The median follow-up time is 96.3 months (mean 97.8, standard deviation 46.7). The best-performing model incorporated both EMR and CCR features. The area under the receiver-operating characteristic curve=0.925 [95% confidence interval: 0.880-0.969], sensitivity=0.861, specificity=0.878 and overall accuracy=0.870. Discussion and Conclusion: A framework for MBC case detection combining EMR and CCR data achieved good sensitivity, specificity and discrimination without requiring expert-labeled examples. This approach enables population-based research on how patients die from cancer and may identify novel predictors of cancer recurrence.
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.
Using histopathological images to automatically classify cancer is a difficult task for accurately detecting cancer, especially to identify metastatic cancer in small image patches obtained from larger digital pathology scans. Computer diagnosis technology has attracted wide attention from researchers. In this paper, we propose a noval method which combines the deep learning algorithm in image classification, the DenseNet169 framework and Rectified Adam optimization algorithm. The connectivity pattern of DenseNet is direct connections from any layer to all consecutive layers, which can effectively improve the information flow between different layers. With the fact that RAdam is not easy to fall into a local optimal solution, and it can converge quickly in model training. The experimental results shows that our model achieves superior performance over the other classical convolutional neural networks approaches, such as Vgg19, Resnet34, Resnet50. In particular, the Auc-Roc score of our DenseNet169 model is 1.77% higher than Vgg19 model, and the Accuracy score is 1.50% higher. Moreover, we also study the relationship between loss value and batches processed during the training stage and validation stage, and obtain some important and interesting findings.
Characterization of breast parenchyma on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging task owing to the complexity of underlying tissue structures. Current quantitative approaches, including radiomics and deep learning models, do not explicitly capture the complex and subtle parenchymal structures, such as fibroglandular tissue. In this paper, we propose a novel method to direct a neural networks attention to a dedicated set of voxels surrounding biologically relevant tissue structures. By extracting multi-dimensional topological structures with high saliency, we build a topology-derived biomarker, TopoTxR. We demonstrate the efficacy of TopoTxR in predicting response to neoadjuvant chemotherapy in breast cancer. Our qualitative and quantitative results suggest differential topological behavior of breast tissue on treatment-naive imaging, in patients who respond favorably to therapy versus those who do not.
Background and Aim: Recently, deep learning using convolutional neural network has been used successfully to classify the images of breast cells accurately. However, the accuracy of manual classification of those histopathological images is comparatively low. This research aims to increase the accuracy of the classification of breast cancer images by utilizing a Patch-Based Classifier (PBC) along with deep learning architecture. Methodology: The proposed system consists of a Deep Convolutional Neural Network (DCNN) that helps in enhancing and increasing the accuracy of the classification process. This is done by the use of the Patch-based Classifier (PBC). CNN has completely different layers where images are first fed through convolutional layers using hyperbolic tangent function together with the max-pooling layer, drop out layers, and SoftMax function for classification. Further, the output obtained is fed to a patch-based classifier that consists of patch-wise classification output followed by majority voting. Results: The results are obtained throughout the classification stage for breast cancer images that are collected from breast-histology datasets. The proposed solution improves the accuracy of classification whether or not the images had normal, benign, in-situ, or invasive carcinoma from 87% to 94% with a decrease in processing time from 0.45 s to 0.2s on average. Conclusion: The proposed solution focused on increasing the accuracy of classifying cancer in the breast by enhancing the image contrast and reducing the vanishing gradient. Finally, this solution for the implementation of the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique and modified tangent function helps in increasing the accuracy.
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