Structured crowdsourcing enables convolutional segmentation of histology images.

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.

In vivo cell-cycle profiling in xenograft tumors by quantitative intravital microscopy.

Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional (3D) 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, which are 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 d in HT-1080 fibrosarcoma xenografts in living mice using a data set of 38,000 cells and compared the induced phenotypes. In contrast to results with 2D culture, observed mitotic arrest was relatively low, suggesting involvement of additional mechanisms in their antitumor effect in vivo.

The Digital Slide Archive: A Software Platform for Management, Integration, and Analysis of Histology for Cancer Research.

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 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 article, 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. Cancer Res; 77(21); e75-78. ©2017 AACR.

An explicit shape-constrained MRF-based contour evolution method for 2-D medical image segmentation.

Image segmentation is, in general, an ill-posed problem and additional constraints need to be imposed in order to achieve the desired segmentation result. While segmenting organs in medical images, which is the topic of this paper, a significant amount of prior knowledge about the shape, appearance, and location of the organs is available that can be used to constrain the solution space of the segmentation problem. Among the various types of prior information, the incorporation of prior information about shape, in particular, is very challenging. In this paper, we present an explicit shape-constrained MAP-MRF-based contour evolution method for the segmentation of organs in 2-D medical images. Specifically, we represent the segmentation contour explicitly as a chain of control points. We then cast the segmentation problem as a contour evolution problem, wherein the evolution of the contour is performed by iteratively solving a MAP-MRF labeling problem. The evolution of the contour is governed by three types of prior information, namely: (i) appearance prior, (ii) boundary-edgeness prior, and (iii) shape prior, each of which is incorporated as clique potentials into the MAP-MRF problem. We use the master-slave dual decomposition framework to solve the MAP-MRF labeling problem in each iteration. In our experiments, we demonstrate the application of the proposed method to the challenging problem of heart segmentation in non-contrast computed tomography data.

Toward the automatic detection of coronary artery calcification in non-contrast computed tomography data.

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.

A supervised classification-based method for coronary calcium detection in non-contrast CT.

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.