Locality sensitive deep learning for detection and classification of nuclei in routine colon cancer histology images

Detection and classification of cell nuclei in histopathology images of cancerous tissue stained with the standard hematoxylin and eosin stain is a challenging task due to cellular heterogeneity. Deep learning approaches have been shown to produce encouraging results on histopathology images in various studies. In this paper, we propose a Spatially Constrained Convolutional Neural Network (SC-CNN) to perform nucleus detection. SC-CNN regresses the likelihood of a pixel being the center of a nucleus, where high probability values are spatially constrained to locate in the vicinity of the center of nuclei. For classification of nuclei, we propose a novel Neighboring Ensemble Predictor (NEP) coupled with CNN to more accurately predict the class label of detected cell nuclei. The proposed approaches for detection and classification do not require segmentation of nuclei. We have evaluated them on a large dataset of colorectal adenocarcinoma images, consisting of more than 20,000 annotated nuclei belonging to four different classes. Our results show that the joint detection and classification of the proposed SC-CNN and NEP produces the highest average F1 score as compared to other recently published approaches. Prospectively, the proposed methods could offer benefit to pathology practice in terms of quantitative analysis of tissue constituents in whole-slide images, and could potentially lead to a better understanding of cancer

Computational Methods for Delineating Multiple Nuclear Phenotypes from Different Imaging Modalities

Characterizing histopathology or organoid models of breast cancer can provide fundamental knowledge that will lead to a better understanding of tumors, response to therapeutic agents, and discovery of new targeted therapies. To this aim, the delineation of nuclei is significantly interesting since it provides rich information about the aberrant microanatomy or colony formation. For example, (i) cancer cells tend to be larger and, if coupled with high chromatin content, may indicate aneuploidy; (ii) cellular density can be the result of rapid proliferation; (iii) nuclear micro-texture can be a surrogate for fluctuation of heterochromatin patterns, where epigenetic aberrations in cancers are sometimes correlated with alterations in heterochromatin distribution; and (iv) normalized colony formation of cancer cells, in 3D culture, can serve as a surrogate metric for tumor suppression. These evidences suggest that nuclear segmentation and profiling is a major step for subsequent bioinformatics analysis. However, there are two barriers which include technical variations during the sample preparation step and biological heterogeneity since no two patients/samples are alike. As a result of these complexities, extension of deep learning methodologies will have a significant impact on the robust characterization and profiling of pathology sections or organoid models. In this presentation, we demonstrate that integration of regional and contextual representations, within the framework of a deep encoder-decoder architecture, contribute to robust delineation of various nuclear phenotypes from both bright field and confocal microscopy. The deep encoder-decoder architecture can infer perceptual boundaries that are necessary to decompose clumps of nuclei. The method has been validated on pathology section and organoid models of human mammary epithelial cells

Nuclei Detection Using Mixture Density Networks

Nuclei detection is an important task in the histology domain as it is a main step toward further analysis such as cell counting, cell segmentation, study of cell connections, etc. This is a challenging task due to the complex texture of histology image, variation in shape, and touching cells. To tackle these hurdles, many approaches have been proposed in the literature where deep learning methods stand on top in terms of performance. Hence, in this paper, we propose a novel framework for nuclei detection based on Mixture Density Networks (MDNs). These networks are suitable to map a single input to several possible outputs and we utilize this property to detect multiple seeds in a single image patch. A new modified form of a cost function is proposed for training and handling patches with missing nuclei. The probability maps of the nuclei in the individual patches are next combined to generate the final image-wide result. The experimental results show the state-of-the-art performance on complex colorectal adenocarcinoma dataset.Comment: 8 pages, 3 figure

Computational Pathology: A Survey Review and The Way Forward

Computational Pathology CPath is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field's future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath (https://github.com/AtlasAnalyticsLab/CPath_Survey).Comment: Accepted in Elsevier Journal of Pathology Informatics (JPI) 202

Deep Learning for Classification of Brain Tumor Histopathological Images

Histopathological image classification has been at the forefront of medical research. We evaluated several deep and non-deep learning models for brain tumor histopathological image classification. The challenges were characterized by an insufficient amount of training data and identical glioma features. We employed transfer learning to tackle these challenges. We also employed some state-of-the-art non-deep learning classifiers on histogram of gradient features extracted from our images, as well as features extracted using CNN activations. Data augmentation was utilized in our study. We obtained an 82% accuracy with DenseNet-201 as our best for the deep learning models and an 83.8% accuracy with ANN for the non-deep learning classifiers. The average of the diagonals of the confusion matrices for each model was calculated as their accuracy. The performance metrics criteria in this study are our model’s precision in classifying each class and their average classification accuracy. Our result emphasizes the significance of deep learning as an invaluable tool for histopathological image studies

Simultaneous cell detection and classification in bone marrow histology images

Recently, deep learning frameworks have been shown to be successful and efficient in processing digital histology images for various detection and classification tasks. Among these tasks, cell detection and classification are key steps in many computer-assisted diagnosis systems. Traditionally, cell detection and classification is performed as a sequence of two consecutive steps by using two separate deep learning networks, one for detection and the other for classification. This strategy inevitably increases the computational complexity of the training stage. In this paper, we propose a synchronized deep autoencoder network for simultaneous detection and classification of cells in bone marrow histology images. The proposed network uses a single architecture to detect the positions of cells and classify the detected cells, in parallel. It uses a curve-support Gaussian model to compute probability maps that allow detecting irregularly-shape cells precisely. Moreover, the network includes a novel neighborhood selection mechanism to boost the classification accuracy. We show that the performance of the proposed network is superior than traditional deep learning detection methods and very competitive compared to traditional deep learning classification networks. Runtime comparison also shows that our network requires less time to be trained

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field