Angel Cruz-Roa

Assessment of algorithms for mitosis detection in breast cancer histopathology images.

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.

A Deep Learning Architecture for Image Representation, Visual Interpretability and Automated Basal-Cell Carcinoma Cancer Detection

This paper presents and evaluates a deep learning architecture for automated basal cell carcinoma cancer detection that integrates (1) image representation learning, (2) image classification and (3) result interpretability. A novel characteristic of this approach is that it extends the deep learning architecture to also include an interpretable layer that highlights the visual patterns that contribute to discriminate between cancerous and normal tissues patterns, working akin to a digital staining which spotlights image regions important for diagnostic decisions. Experimental evaluation was performed on set of 1,417 images from 308 regions of interest of skin histopathology slides, where the presence of absence of basal cell carcinoma needs to be determined. Different image representation strategies, including bag of features (BOF), canonical (discrete cosine transform (DCT) and Haar-based wavelet transform (Haar)) and proposed learned-from-data representations, were evaluated for comparison. Experimental results show that the representation learned from a large histology image data set has the best overall performance (89.4% in F-measure and 91.4% in balanced accuracy), which represents an improvement of around 7% over canonical representations and 3% over the best equivalent BOF representation.

Visual pattern mining in histology image collections using bag of features.

OBJECTIVE The paper addresses the problem of finding visual patterns in histology image collections. In particular, it proposes a method for correlating basic visual patterns with high-level concepts combining an appropriate image collection representation with state-of-the-art machine learning techniques. METHODOLOGY The proposed method starts by representing the visual content of the collection using a bag-of-features strategy. Then, two main visual mining tasks are performed: finding associations between visual-patterns and high-level concepts, and performing automatic image annotation. Associations are found using minimum-redundancy-maximum-relevance feature selection and co-clustering analysis. Annotation is done by applying a support-vector-machine classifier. Additionally, the proposed method includes an interpretation mechanism that associates concept annotations with corresponding image regions. The method was evaluated in two data sets: one comprising histology images from the different four fundamental tissues, and the other composed of histopathology images used for cancer diagnosis. Different visual-word representations and codebook sizes were tested. The performance in both concept association and image annotation tasks was qualitatively and quantitatively evaluated. RESULTS The results show that the method is able to find highly discriminative visual features and to associate them to high-level concepts. In the annotation task the method showed a competitive performance: an increase of 21% in f-measure with respect to the baseline in the histopathology data set, and an increase of 47% in the histology data set. CONCLUSIONS The experimental evidence suggests that the bag-of-features representation is a good alternative to represent visual content in histology images. The proposed method exploits this representation to perform visual pattern mining from a wider perspective where the focus is the image collection as a whole, rather than individual images.

Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features

Abstract. Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is the mitotic count, which involves quantifying the number of cells in the process of dividing (i.e., undergoing mitosis) at a specific point in time. Currently, mitosis counting is done manually by a pathologist looking at multiple high power fields (HPFs) on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical, or textural attributes of mitoses or features learned with convolutional neural networks (CNN). Although handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely supervised feature generation methods, there is an appeal in attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. We present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color, and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing the performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 HPFs (400× magnification) by several pathologists and 15 testing HPFs yielded an F-measure of 0.7345. Our approach is accurate, fast, and requires fewer computing resources compared to existent methods, making this feasible for clinical use.

Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks

This paper presents a deep learning approach for automatic detection and visual analysis of invasive ductal carcinoma (IDC) tissue regions in whole slide images (WSI) of breast cancer (BCa). Deep learning approaches are learn-from-data methods involving computational modeling of the learning process. This approach is similar to how human brain works using different interpretation levels or layers of most representative and useful features resulting into a hierarchical learned representation. These methods have been shown to outpace traditional approaches of most challenging problems in several areas such as speech recognition and object detection. Invasive breast cancer detection is a time consuming and challenging task primarily because it involves a pathologist scanning large swathes of benign regions to ultimately identify the areas of malignancy. Precise delineation of IDC in WSI is crucial to the subsequent estimation of grading tumor aggressiveness and predicting patient outcome. DL approaches are particularly adept at handling these types of problems, especially if a large number of samples are available for training, which would also ensure the generalizability of the learned features and classifier. The DL framework in this paper extends a number of convolutional neural networks (CNN) for visual semantic analysis of tumor regions for diagnosis support. The CNN is trained over a large amount of image patches (tissue regions) from WSI to learn a hierarchical part-based representation. The method was evaluated over a WSI dataset from 162 patients diagnosed with IDC. 113 slides were selected for training and 49 slides were held out for independent testing. Ground truth for quantitative evaluation was provided via expert delineation of the region of cancer by an expert pathologist on the digitized slides. The experimental evaluation was designed to measure classifier accuracy in detecting IDC tissue regions in WSI. Our method yielded the best quantitative results for automatic detection of IDC regions in WSI in terms of F-measure and balanced accuracy (71.80%, 84.23%), in comparison with an approach using handcrafted image features (color, texture and edges, nuclear textural and architecture), and a machine learning classifier for invasive tumor classification using a Random Forest. The best performing handcrafted features were fuzzy color histogram (67.53%, 78.74%) and RGB histogram (66.64%, 77.24%). Our results also suggest that at least some of the tissue classification mistakes (false positives and false negatives) were less due to any fundamental problems associated with the approach, than the inherent limitations in obtaining a very highly granular annotation of the diseased area of interest by an expert pathologist.

Cascaded ensemble of convolutional neural networks and handcrafted features for mitosis detection

Breast cancer (BCa) grading plays an important role in predicting disease aggressiveness and patient outcome. A key component of BCa grade is mitotic count, which involves quantifying the number of cells in the process of dividing (i.e. undergoing mitosis) at a specific point in time. Currently mitosis counting is done manually by a pathologist looking at multiple high power fields on a glass slide under a microscope, an extremely laborious and time consuming process. The development of computerized systems for automated detection of mitotic nuclei, while highly desirable, is confounded by the highly variable shape and appearance of mitoses. Existing methods use either handcrafted features that capture certain morphological, statistical or textural attributes of mitoses or features learned with convolutional neural networks (CNN). While handcrafted features are inspired by the domain and the particular application, the data-driven CNN models tend to be domain agnostic and attempt to learn additional feature bases that cannot be represented through any of the handcrafted features. On the other hand, CNN is computationally more complex and needs a large number of labeled training instances. Since handcrafted features attempt to model domain pertinent attributes and CNN approaches are largely unsupervised feature generation methods, there is an appeal to attempting to combine these two distinct classes of feature generation strategies to create an integrated set of attributes that can potentially outperform either class of feature extraction strategies individually. In this paper, we present a cascaded approach for mitosis detection that intelligently combines a CNN model and handcrafted features (morphology, color and texture features). By employing a light CNN model, the proposed approach is far less demanding computationally, and the cascaded strategy of combining handcrafted features and CNN-derived features enables the possibility of maximizing performance by leveraging the disconnected feature sets. Evaluation on the public ICPR12 mitosis dataset that has 226 mitoses annotated on 35 High Power Fields (HPF, x400 magnification) by several pathologists and 15 testing HPFs yielded an F-measure of 0.7345. Apart from this being the second best performance ever recorded for this MITOS dataset, our approach is faster and requires fewer computing resources compared to extant methods, making this feasible for clinical use.

An unsupervised feature learning framework for basal cell carcinoma image analysis

OBJECTIVE The paper addresses the problem of automatic detection of basal cell carcinoma (BCC) in histopathology images. In particular, it proposes a framework to both, learn the image representation in an unsupervised way and visualize discriminative features supported by the learned model. MATERIALS AND METHODS This paper presents an integrated unsupervised feature learning (UFL) framework for histopathology image analysis that comprises three main stages: (1) local (patch) representation learning using different strategies (sparse autoencoders, reconstruct independent component analysis and topographic independent component analysis (TICA), (2) global (image) representation learning using a bag-of-features representation or a convolutional neural network, and (3) a visual interpretation layer to highlight the most discriminant regions detected by the model. The integrated unsupervised feature learning framework was exhaustively evaluated in a histopathology image dataset for BCC diagnosis. RESULTS The experimental evaluation produced a classification performance of 98.1%, in terms of the area under receiver-operating-characteristic curve, for the proposed framework outperforming by 7% the state-of-the-art discrete cosine transform patch-based representation. CONCLUSIONS The proposed UFL-representation-based approach outperforms state-of-the-art methods for BCC detection. Thanks to its visual interpretation layer, the method is able to highlight discriminative tissue regions providing a better diagnosis support. Among the different UFL strategies tested, TICA-learned features exhibited the best performance thanks to its ability to capture low-level invariances, which are inherent to the nature of the problem.

Automatic annotation of histopathological images using a latent topic model based on non-negative matrix factorization

Histopathological images are an important resource for clinical diagnosis and biomedical research. From an image understanding point of view, the automatic annotation of these images is a challenging problem. This paper presents a new method for automatic histopathological image annotation based on three complementary strategies, first, a part-based image representation, called the bag of features, which takes advantage of the natural redundancy of histopathological images for capturing the fundamental patterns of biological structures, second, a latent topic model, based on non-negative matrix factorization, which captures the high-level visual patterns hidden in the image, and, third, a probabilistic annotation model that links visual appearance of morphological and architectural features associated to 10 histopathological image annotations. The method was evaluated using 1,604 annotated images of skin tissues, which included normal and pathological architectural and morphological features, obtaining a recall of 74% and a precision of 50%, which improved a baseline annotation method based on support vector machines in a 64% and 24%, respectively.

A visual latent semantic approach for automatic analysis and interpretation of anaplastic medulloblastoma virtual slides

A method for automatic analysis and interpretation of histopathology images is presented. The method uses a representation of the image data set based on bag of features histograms built from visual dictionary of Haar-based patches and a novel visual latent semantic strategy for characterizing the visual content of a set of images. One important contribution of the method is the provision of an interpretability layer, which is able to explain a particular classification by visually mapping the most important visual patterns associated with such classification. The method was evaluated on a challenging problem involving automated discrimination of medulloblastoma tumors based on image derived attributes from whole slide images as anaplastic or non-anaplastic. The data set comprised 10 labeled histopathological patient studies, 5 for anaplastic and 5 for non-anaplastic, where 750 square images cropped randomly from cancerous region from whole slide per study. The experimental results show that the new method is competitive in terms of classification accuracy achieving 0.87 in average.

Combining Unsupervised Feature Learning and Riesz Wavelets for Histopathology Image Representation: Application to Identifying Anaplastic Medulloblastoma

Medulloblastoma MB is a type of brain cancer that represent roughly 25% of all brain tumors in children. In the anaplastic medulloblastoma subtype, it is important to identify the degree of irregularity and lack of organizations of cells as this correlates to disease aggressiveness and is of clinical value when evaluating patient prognosis. This paper presents an image representation to distinguish these subtypes in histopathology slides. The approach combines learned features from i an unsupervised feature learning method using topographic independent component analysis that captures scale, color and translation invariances, and ii learned linear combinations of Riesz wavelets calculated at several orders and scales capturing the granularity of multiscale rotation-covariant information. The contribution of this work is to show that the combination of two complementary approaches for feature learning unsupervised and supervised improves the classification performance. Our approach outperforms the best methods in literature with statistical significance, achieving 99% accuracy over region-based data comprising 7,500 square regions from 10 patient studies diagnosed with medulloblastoma 5 anaplastic and 5 non-anaplastic.