Motivation While deep-learning algorithms have demonstrated outstanding performance in semantic image segmentation tasks, large annotation datasets are needed to create accurate models. Annotation of histology images is challenging due to the effort and experience required to carefully delineate tissue structures, and difficulties related to sharing and markup of whole-slide images. Results We recruited 25 participants, ranging in experience from senior pathologists to medical students, to delineate tissue regions in 151 breast cancer slides using the Digital Slide Archive. Inter-participant discordance was systematically evaluated, revealing low discordance for tumor and stroma, and higher discordance for more subjectively defined or rare tissue classes. Feedback provided by senior participants enabled the generation and curation of 20 000+ annotated tissue regions. Fully convolutional networks trained using these annotations were highly accurate (mean AUC=0.945), and the scale of annotation data provided notable improvements in image classification accuracy. Availability and Implementation Dataset is freely available at: https://goo.gl/cNM4EL. Supplementary information Supplementary data are available at Bioinformatics online.
Tissue based cancer studies can generate large amounts of histology data in the form of glass slides. These slides contain important diagnostic, prognostic, and biological information, and can be digitized into expansive and high-resolution whole-slide images (WSI) using slide-scanning devices. Effectively utilizing digital pathology data in cancer research requires the ability to manage, visualize, share and perform quantitative analysis on these large amounts of image data, tasks that are often complex and difficult for investigators with the current state of commercial digital pathology software. In this paper we describe the Digital Slide Archive (DSA), an open source web-based platform for digital pathology. DSA allows investigators to manage large collections of histologic images and integrate them with clinical and genomic metadata. The open-source model enables DSA to be extended to provide additional capabilities.
Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional biological processes such as tissue development and cancer. Analysis of 3D in vivo images, however, is very challenging. Today’s best practice, manual annotation of select image events, generates arbitrarily sampled data distributions, unsuitable for reliable mechanistic inferences. Here, we present an integrated workflow for quantitative in vivo cell-cycle profiling. It combines image analysis and machine learning methods for automated 3D segmentation and cell-cycle state identification of individual cell-nuclei with widely varying morphologies embedded in complex tumor environments. We applied our workflow to quantify cell-cycle effects of three antimitotic cancer drugs over 8 days in HT-1080 fibrosarcoma xenografts in living mice using a dataset of 38,000 cells and compared the induced phenotypes. In contrast to 2D culture, observed mitotic arrest was relatively low, suggesting involvement of additional mechanisms in their antitumor effect in vivo.
Accurate quantification of coronary artery calcium provides an opportunity to assess the extent of atherosclerosis disease. Coronary calcification burden has been reported to be associated with cardiovascular risk. Currently, an observer has to identify the coronary calcifications among a set of candidate regions, obtained by thresholding and connected component labeling, by clicking on them. To relieve the observer of such a labor-intensive task, an automated tool is needed that can detect and quantify the coronary calcifications. However, the diverse and heterogeneous nature of the candidate regions poses a significant challenge. In this paper, we investigate a supervised classification-based approach to distinguish the coronary calcifications from all the candidate regions and propose a two-stage, hierarchical classifier for automated coronary calcium detection. At each stage, we learn an ensemble of classifiers where each classifier is a cost-sensitive learner trained on a distinct asymmetrically sampled data subset. We compute the relative location of the calcifications with respect to a heart-centered coordinate system, and also use the neighboring regions of the calcifications to better characterize their properties for discrimination. Our method detected coronary calcifications with an accuracy, sensitivity and specificity of 98.27, 92.07 and 98.62%, respectively, for a testing dataset of non-contrast computed tomography scans from 105 subjects.
Measurements related to coronary artery calcification (CAC) offer significant predictive value for coronary artery disease (CAD). In current medical practice CAC scoring is a labor-intensive task. The objective of this paper is the development and evaluation of a family of coronary artery region (CAR) models applied to the detection of CACs in coronary artery zones and sections. Thirty patients underwent non-contrast electron-beam computed tomography scanning. Coronary artery trajectory points as presented in the University of Houston heart-centered coordinate system were utilized to construct the CAR models which automatically detect coronary artery zones and sections. On a per-patient and per-zone basis the proposed CAR models detected CACs with a sensitivity, specificity and accuracy of 85.56 (± 15.80)%, 93.54 (± 1.98)%, and 85.27 (± 14.67)%, respectively while the corresponding values in the zones and segments based case were 77.94 (± 7.78)%, 96.57 (± 4.90)%, and 73.58 (± 8.96)%, respectively. The results of this study suggest that the family of CAR models provide an effective method to detect different regions of the coronaries. Further, the CAR classifiers are able to detect CACs with a mean sensitivity and specificity of 86.33 and 93.78%, respectively.
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