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Histo-CADx: duo cascaded fusion stages for breast cancer diagnosis from histopathological images.

ABSTRACT: Breast cancer (BC) is one of the most common types of cancer that affects females worldwide. It may lead to irreversible complications and even death due to late diagnosis and treatment. The pathological analysis is considered the gold standard for BC detection, but it is a challenging task. Automatic diagnosis of BC could reduce death rates, by creating a computer aided diagnosis (CADx) system capable of accurately identifying BC at an early stage and decreasing the time consumed by pathologists during examinations. This paper proposes a novel CADx system named Histo-CADx for the automatic diagnosis of BC. Most related studies were based on individual deep learning methods. Also, studies did not examine the influence of fusing features from multiple CNNs and handcrafted features. In addition, related studies did not investigate the best combination of fused features that influence the performance of the CADx. Therefore, Histo-CADx is based on two stages of fusion. The first fusion stage involves the investigation of the impact of fusing several deep learning (DL) techniques with handcrafted feature extraction methods using the auto-encoder DL method. This stage also examines and searches for a suitable set of fused features that could improve the performance of Histo-CADx. The second fusion stage constructs a multiple classifier system (MCS) for fusing outputs from three classifiers, to further improve the accuracy of the proposed Histo-CADx. The performance of Histo-CADx is evaluated using two public datasets; specifically, the BreakHis and the ICIAR 2018 datasets. The results from the analysis of both datasets verified that the two fusion stages of Histo-CADx successfully improved the accuracy of the CADx compared to CADx constructed with individual features. Furthermore, using the auto-encoder for the fusion process has reduced the computation cost of the system. Moreover, the results after the two fusion stages confirmed that Histo-CADx is reliable and has the capacity of classifying BC more accurately compared to other latest studies. Consequently, it can be used by pathologists to help them in the accurate diagnosis of BC. In addition, it can decrease the time and effort needed by medical experts during the examination.

SUBMITTER: Attallah O

PROVIDER: S-EPMC8093954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Breast cancer is associated with the highest morbidity rates for cancer diagnoses in the world and has become a major public health issue. Early diagnosis can increase the chance of successful treatment and survival. However, it is a very challenging and time-consuming task that relies on the experience of pathologists. The automatic diagnosis of breast cancer by analyzing histopathological images plays a significant role for patients and their prognosis. However, traditional feature extraction methods can only extract some low-level features of images, and prior knowledge is necessary to select useful features, which can be greatly affected by humans. Deep learning techniques can extract high-level abstract features from images automatically. Therefore, we introduce it to analyze histopathological images of breast cancer via supervised and unsupervised deep convolutional neural networks. First, we adapted Inception_V3 and Inception_ResNet_V2 architectures to the binary and multi-class issues of breast cancer histopathological image classification by utilizing transfer learning techniques. Then, to overcome the influence from the imbalanced histopathological images in subclasses, we balanced the subclasses with Ductal Carcinoma as the baseline by turning images up and down, right and left, and rotating them counterclockwise by 90 and 180 degrees. Our experimental results of the supervised histopathological image classification of breast cancer and the comparison to the results from other studies demonstrate that Inception_V3 and Inception_ResNet_V2 based histopathological image classification of breast cancer is superior to the existing methods. Furthermore, these findings show that Inception_ResNet_V2 network is the best deep learning architecture so far for diagnosing breast cancers by analyzing histopathological images. Therefore, we used Inception_ResNet_V2 to extract features from breast cancer histopathological images to perform unsupervised analysis of the images. We also constructed a new autoencoder network to transform the features extracted by Inception_ResNet_V2 to a low dimensional space to do clustering analysis of the images. The experimental results demonstrate that using our proposed autoencoder network results in better clustering results than those based on features extracted only by Inception_ResNet_V2 network. All of our experimental results demonstrate that Inception_ResNet_V2 network based deep transfer learning provides a new means of performing analysis of histopathological images of breast cancer.

Project description:BackgroundExisting studies have demonstrated that the integrative analysis of histopathological images and genomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, since the development of pathological phenotypes are influenced by a variety of complex biological processes, complete understanding of the underlying gene regulatory mechanisms for the cell and tissue morphology is still a challenge. In this study, we explored the relationship between the chromatin accessibility changes and the epithelial tissue proportion in histopathological images of estrogen receptor (ER) positive breast cancer.MethodsAn established whole slide image processing pipeline based on deep learning was used to perform global segmentation of epithelial and stromal tissues. We then used canonical correlation analysis to detect the epithelial tissue proportion-associated regulatory regions. By integrating ATAC-seq data with matched RNA-seq data, we found the potential target genes that associated with these regulatory regions. Then we used these genes to perform the following pathway and survival analysis.ResultsUsing canonical correlation analysis, we detected 436 potential regulatory regions that exhibited significant correlation between quantitative chromatin accessibility changes and the epithelial tissue proportion in tumors from 54 patients (FDR < 0.05). We then found that these 436 regulatory regions were associated with 74 potential target genes. After functional enrichment analysis, we observed that these potential target genes were enriched in cancer-associated pathways. We further demonstrated that using the gene expression signals and the epithelial tissue proportion extracted from this integration framework could stratify patient prognoses more accurately, outperforming predictions based on only omics or image features.ConclusionThis integrative analysis is a useful strategy for identifying potential regulatory regions in the human genome that are associated with tumor tissue quantification. This study will enable efficient prioritization of genomic regulatory regions identified by ATAC-seq data for further studies to validate their causal regulatory function. Ultimately, identifying epithelial tissue proportion-associated regulatory regions will further our understanding of the underlying molecular mechanisms of disease and inform the development of potential therapeutic targets.

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Project description:Cervical cancer is one of the most common types of malignant tumors in women. In addition, it causes death in the latter stages. Squamous cell carcinoma is the most common and aggressive form of cervical cancer and must be diagnosed early before it progresses to a dangerous stage. Liquid-based cytology (LBC) swabs are best and most commonly used for cervical cancer screening and are converted from glass slides to whole-slide images (WSIs) for computer-assisted analysis. Manual diagnosis by microscopes is limited and prone to manual errors, and tracking all cells is difficult. Therefore, the development of computational techniques is important as diagnosing many samples can be done automatically, quickly, and efficiently, which is beneficial for medical laboratories and medical professionals. This study aims to develop automated WSI image analysis models for early diagnosis of a cervical squamous cell dataset. Several systems have been designed to analyze WSI images and accurately distinguish cervical cancer progression. For all proposed systems, the WSI images were optimized to show the contrast of edges of the low-contrast cells. Then, the cells to be analyzed were segmented and isolated from the rest of the image using the Active Contour Algorithm (ACA). WSI images were diagnosed by a hybrid method between deep learning (ResNet50, VGG19 and GoogLeNet), Random Forest (RF), and Support Vector Machine (SVM) algorithms based on the ACA algorithm. Another hybrid method for diagnosing WSI images by RF and SVM algorithms is based on fused features of deep-learning (DL) models (ResNet50-VGG19, VGG19-GoogLeNet, and ResNet50-GoogLeNet). It is concluded from the systems' performance that the DL models' combined features help significantly improve the performance of the RF and SVM networks. The novelty of this research is the hybrid method that combines the features extracted from deep-learning models (ResNet50-VGG19, VGG19-GoogLeNet, and ResNet50-GoogLeNet) with RF and SVM algorithms for diagnosing WSI images. The results demonstrate that the combined features from deep-learning models significantly improve the performance of RF and SVM. The RF network with fused features of ResNet50-VGG19 achieved an AUC of 98.75%, a sensitivity of 97.4%, an accuracy of 99%, a precision of 99.6%, and a specificity of 99.2%.

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Histo-CADx: duo cascaded fusion stages for breast cancer diagnosis from histopathological images.

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