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Register a new userUnderstanding the Mechanism of Deep Learning Framework for Lesion Detection in Pathological Images with Breast Cancer
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Added by
Wei-Wen Hsu
Publication date
2019
fields
Informatics Engineering
and research's language is
English
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The computer-aided detection (CADe) systems are developed to assist pathologists in slide assessment, increasing diagnosis efficiency and reducing missing inspections. Many studies have shown such a CADe system with deep learning approaches outperforms the one using conventional methods that rely on hand-crafted features based on field-knowledge. However, most developers who adopted deep learning models directly focused on the efficacy of outcomes, without providing comprehensive explanations on why their proposed frameworks can work effectively. In this study, we designed four experiments to verify the consecutive concepts, showing that the deep features learned from pathological patches are interpretable by domain knowledge of pathology and enlightening for clinical diagnosis in the task of lesion detection. The experimental results show the activation features work as morphological descriptors for specific cells or tissues, which agree with the clinical rules in classification. That is, the deep learning framework not only detects the distribution of tumor cells but also recognizes lymphocytes, collagen fibers, and some other non-cell structural tissues. Most of the characteristics learned by the deep learning models have summarized the detection rules that can be recognized by the experienced pathologists, whereas there are still some features may not be intuitive to domain experts but discriminative in classification for machines. Those features are worthy to be further studied in order to find out the reasonable correlations to pathological knowledge, from which pathological experts may draw inspirations for exploring new characteristics in diagnosis.
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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.
Convolutional Neural Networks (CNN) have had a huge success in many areas of computer vision and medical image analysis. However, there is still an immense potential for performance improvement in mammogram breast cancer detection Computer-Aided Detection (CAD) systems by integrating all the information that the radiologist utilizes, such as symmetry and temporal data. In this work, we proposed a patch based multi-input CNN that learns symmetrical difference to detect breast masses. The network was trained on a large-scale dataset of 28294 mammogram images. The performance was compared to a baseline architecture without symmetry context using Area Under the ROC Curve (AUC) and Competition Performance Metric (CPM). At candidate level, AUC value of 0.933 with 95% confidence interval of [0.920, 0.954] was obtained when symmetry information is incorporated in comparison with baseline architecture which yielded AUC value of 0.929 with [0.919, 0.947] confidence interval. By incorporating symmetrical information, although there was no a significant candidate level performance again (p = 0.111), we have found a compelling result at exam level with CPM value of 0.733 (p = 0.001). We believe that including temporal data, and adding benign class to the dataset could improve the detection performance.
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.
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.
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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