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.

A Feature-based Affine Registration Method for Capturing Background Lung Tissue Deformation for Ground Glass Nodule Tracking.

Lung nodule tracking assessment relies on cross-sectional measurements of the largest lesion profile depicted in initial and follow-up computed tomography (CT) images. However, apparent changes in nodule size assessed via simple image-based measurements may also be compromised by the effect of the background lung tissue deformation on the GGN between the initial and follow-up images, leading to erroneous conclusions about nodule changes due to disease. To compensate for the lung deformation and enable consistent nodule tracking, here we propose a feature-based affine registration method and study its performance vis-a-vis several other registration methods. We implement and test each registration method using both a lung- and a lesion-centered region of interest on ten patient CT datasets featuring twelve nodules, including both benign and malignant GGO lesions containing pure GGNs, part-solid, or solid nodules. We evaluate each registration method according to the target registration error (TRE) computed across 30 - 50 homologous fiducial landmarks surrounding the lesions and selected by expert radiologists in both the initial and follow-up patient CT images. Our results show that the proposed feature-based affine lesion-centered registration yielded a 1.1 ± 1.2 mm TRE, while a Symmetric Normalization deformable registration yielded a 1.2 ± 1.2 mm TRE, and a least-square fit registration of the 30-50 validation fiducial landmark set yielded a 1.5 ± 1.2 mm TRE. Although the deformable registration yielded a slightly higher registration accuracy than the feature-based affine registration, it is significantly more computationally efficient, eliminates the need for ambiguous segmentation of GGNs featuring ill-defined borders, and reduces the susceptibility of artificial deformations introduced by the deformable registration, which may lead to increased similarity between the registered initial and follow-up images, over-compensating for the background lung tissue deformation, and, in turn, compromising the true disease-induced nodule change assessment. We also assessed the registration qualitatively, by visual inspection of the subtraction images, and conducted a pilot pre-clinical study that showed the proposed feature-based lesion-centered affine registration effectively compensates for the background lung tissue deformation between the initial and follow-up images and also serves as a reliable baseline registration method prior to assessing lung nodule changes due to disease.

Real-time Burn Classification using Ultrasound Imaging.

This article presents a real-time approach for classification of burn depth based on B-mode ultrasound imaging. A grey-level co-occurrence matrix (GLCM) computed from the ultrasound images of the tissue is employed to construct the textural feature set and the classification is performed using nonlinear support vector machine and kernel Fisher discriminant analysis. A leave-one-out cross-validation is used for the independent assessment of the classifiers. The model is tested for pair-wise binary classification of four burn conditions in ex vivo porcine skin tissue: (i) 200 °F for 10 s, (ii) 200 °F for 30 s, (iii) 450 °F for 10 s, and (iv) 450 °F for 30 s. The average classification accuracy for pairwise separation is 99% with just over 30 samples in each burn group and the average multiclass classification accuracy is 93%. The results highlight that the ultrasound imaging-based burn classification approach in conjunction with the GLCM texture features provide an accurate assessment of altered tissue characteristics with relatively moderate sample sizes, which is often the case with experimental and clinical datasets. The proposed method is shown to have the potential to assist with the real-time clinical assessment of burn degrees, particularly for discriminating between superficial and deep second degree burns, which is challenging in clinical practice.

Image-Based Methods for Phase Estimation, Gating, and Temporal Superresolution of Cardiac Ultrasound.

OBJECTIVE: Ultrasound is an effective tool for rapid noninvasive assessment of cardiac structure and function. Determining the cardiorespiratory phases of each frame in the ultrasound video and capturing the cardiac function at a much higher temporal resolution are essential in many applications. Fulfilling these requirements is particularly challenging in preclinical studies involving small animals with high cardiorespiratory rates, requiring cumbersome and expensive specialized hardware. METHODS: We present a novel method for the retrospective estimation of cardiorespiratory phases directly from the ultrasound videos. It transforms the videos into a univariate time series preserving the evidence of periodic cardiorespiratory motion, decouples the signatures of cardiorespiratory motion with a trend extraction technique, and estimates the cardiorespiratory phases using a Hilbert transform approach. We also present a robust nonparametric regression technique for respiratory gating and a novel kernel-regression model for reconstructing images at any cardiac phase facilitating temporal superresolution. RESULTS: We validated our methods using two-dimensional echocardiography videos and electrocardiogram (ECG) recordings of six mice. Our cardiac phase estimation method provides accurate phase estimates with a mean-phase-error range of 3%-6% against ECG derived phase and outperforms three previously published methods in locating ECGs R-wave peak frames with a mean-frame-error range of 0.73-1.36. Our kernel-regression model accurately reconstructs images at any cardiac phase with a mean-normalized-correlation range of 0.81-0.85 over 50 leave-one-out-cross-validation rounds. CONCLUSION AND SIGNIFICANCE: Our methods can enable tracking of cardiorespiratory phases without additional hardware and reconstruction of respiration-free single cardiac-cycle videos at a much higher temporal resolution.

Automatic quantification framework to detect cracks in teeth.

Studies show that cracked teeth are the third most common cause for tooth loss in industrialized countries. If detected early and accurately, patients can retain their teeth for a longer time. Most cracks are not detected early because of the discontinuous symptoms and lack of good diagnostic tools. Currently used imaging modalities like Cone Beam Computed Tomography (CBCT) and intraoral radiography often have low sensitivity and do not show cracks clearly. This paper introduces a novel method that can detect, quantify, and localize cracks automatically in high resolution CBCT (hr-CBCT) scans of teeth using steerable wavelets and learning methods. These initial results were created using hr-CBCT scans of a set of healthy teeth and of teeth with simulated longitudinal cracks. The cracks were simulated using multiple orientations. The crack detection was trained on the most significant wavelet coefficients at each scale using a bagged classifier of Support Vector Machines. Our results show high discriminative specificity and sensitivity of this method. The framework aims to be automatic, reproducible, and open-source. Future work will focus on the clinical validation of the proposed techniques on different types of cracks ex-vivo. We believe that this work will ultimately lead to improved tracking and detection of cracks allowing for longer lasting healthy teeth.

SCOLIOSIS SCREENING AND MONITORING USING SELF CONTAINED ULTRASOUND AND NEURAL NETWORKS.

We aim to diagnose scoliosis using a self contained ultrasound device that does not require significant training to operate. The device knows its angle relative to vertical using an embedded inertial measurement unit, and it estimates its angle relative to a vertebrae using a neural network analysis of its ultrasound images. The composition of those angles defines the angle of a vertebrae from vertical. The maximum difference between vertebrae angles collected from a scan of a spine yields the Cobb angle measure that is used to quantify scoliosis severity.

Ultrasound Augmentation: Rapid 3-D Scanning for Tracking and On-Body Display.

By using a laser projector and high speed camera, we can add three capabilities to an ultrasound system: tracking the probe, tracking the patient, and projecting information onto the probe and patient. We can use these capabilities to guide an untrained operator to take high quality, well framed ultrasound images for computer-augmented, point-of-care ultrasound applications.

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.

Automatic Estimation of the Optic Nerve Sheath Diameter from Ultrasound Images.

We present an algorithm to automatically estimate the diameter of the optic nerve sheath from ocular ultrasound images. The optic nerve sheath diameter provides a proxy for measuring intracranial pressure, a life threating condition frequently associated with head trauma. Early treatment of elevated intracranial pressures greatly improves outcomes and drastically reduces the mortality rate. We demonstrate that the proposed algorithm combined with a portable ultrasound device presents a viable path for early detection of elevated intracranial pressure in remote locations and without access to trained medical imaging experts.

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.