Image Analysis

The morphological effect of impurities on α-U₃O₈ has been investigated. This study provides the first evidence that the presence of impurities can alter nuclear material morphology, and these changes can be quantified to aid in revealing processing history. Four elements: Ca, Mg, V, and Zr were implemented in the uranyl peroxide synthesis route and studied individually within the α-U₃O₈. Six total replicates were synthesized, and replicates 1–3 were filtered and washed with Millipore water (18.2 MΩ) to remove any residual nitrates. Replicates 4–6 were filtered but not washed to determine the amount of impurities removed during washing. Inductively coupled plasma mass spectrometry (ICP-MS) was employed at key points during the synthesis to quantify incorporation of the impurity. Each sample was characterized using powder X-ray diffraction (p-XRD), high-resolution scanning electron microscopy (HRSEM), and SEM with energy dispersive X-ray spectroscopy (SEM-EDS). p-XRD was utilized to evaluate any crystallographic changes due to the impurities; HRSEM imagery was analyzed with Morphological Analysis for MAterials (MAMA) software and machine learning classification for quantification of the morphology; and SEM-EDS was utilized to locate the impurity within the α-U₃O₈. All samples were found to be quantifiably distinguishable, further demonstrating the utility of quantitative morphology as a signature for the processing history of nuclear material.

BACKGROUND:
Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.

To conduct computational forward and inverse EEG studies of brain electrical activity, researchers must construct realistic head and brain computer models, which is both challenging and time consuming. The availability of realistic head models and corresponding imaging data is limited in terms of imaging modalities and patient diversity. In this paper, we describe a detailed head modeling pipeline and provide a high-resolution, multimodal, open-source, female head and brain model. The modeling pipeline specifically outlines image acquisition, preprocessing, registration, and segmentation; three-dimensional tetrahedral mesh generation; finite element EEG simulations; and visualization of the model and simulation results. The dataset includes both functional and structural images and EEG recordings from two high-resolution electrode configurations. The intermediate results and software components are also included in the dataset to facilitate modifications to the pipeline. This project will contribute to neuroscience research by providing a high-quality dataset that can be used for a variety of applications and a computational pipeline that may help researchers construct new head models more efficiently.

Semi-supervised learning (SSL) has become important in current data analysis applications, where the amount of unlabeled data is growing exponentially and user input remains limited by logistics and expense. Constrained clustering, as a subclass of SSL, makes use of user input in the form of relationships between data points (e.g., pairs of data points belonging to the same class or different classes) and can remarkably improve the performance of unsupervised clustering in order to reflect user-defined knowledge of the relationships between particular data points. Existing algorithms incorporate such user input, heuristically, as either hard constraints or soft penalties, which are separate from any generative or statistical aspect of the clustering model; this results in formulations that are suboptimal and not sufficiently general. In this paper, we propose a principled, generative approach to probabilistically model, without ad hoc penalties, the joint distribution given by user-defined pairwise relations. The proposed model accounts for general underlying distributions without assuming a specific form and relies on expectation-maximization for model fitting. For distributions in a standard form, the proposed approach results in a closed-form solution for updated parameters.

Given data, deep generative models, such as variational autoencoders (VAE) and generative adversarial networks (GAN), train a lower dimensional latent representation of the data space. The linear Euclidean geometry of data space pulls back to a nonlinear Riemannian geometry on the latent space. The latent space thus provides a low-dimensional nonlinear representation of data and classical linear statistical techniques are no longer applicable. In this paper we show how statistics of data in their latent space representation can be performed using techniques from the field of nonlinear manifold statistics. Nonlinear manifold statistics provide generalizations of Euclidean statistical notions including means, principal component analysis, and maximum likelihood fits of parametric probability distributions. We develop new techniques for maximum likelihood inference in latent space, and adress the computational complexity of using geometric algorithms with high-dimensional data by training a separate neural network to approximate the Riemannian metric and cometric tensor capturing the shape of the learned data manifold.

We present a novel approach for improving the shape statistics of medical image objects by generating correspondence of skeletal points. Each object's interior is modeled by an s-rep, i.e., by a sampled, folded, two-sided skeletal sheet with spoke vectors proceeding from the skeletal sheet to the boundary. The skeleton is divided into three parts: the up side, the down side, and the fold curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along that skeleton in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface/boundary-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and the sampling regularity, here of the spokes' geometric properties. Evaluation on synthetic and real world lateral ventricle and hippocampus data sets demonstrate improvement in the performance of statistics using the resulting probability distributions. This improvement is greater than that achieved by an entropy-based correspondence method on the boundary points.

The use of appearance and shape priors in image segmentation is known to improve accuracy; however, existing techniques have several drawbacks. For instance, most active shape and appearance models require landmark points and assume unimodal shape and appearance distributions, and the level set representation does not support construction of local priors. In this paper, we present novel appearance and shape models for image segmentation based on a differentiable implicit parametric shape representation called a disjunctive normal shape model (DNSM). The DNSM is formed by the disjunction of polytopes, which themselves are formed by the conjunctions of half-spaces. The DNSM's parametric nature allows the use of powerful local prior statistics, and its implicit nature removes the need to use landmarks and easily handles topological changes. In a Bayesian inference framework, we model arbitrary shape and appearance distributions using nonparametric density estimations, at any local scale. The proposed local shape prior results in accurate segmentation even when very few training shapes are available, because the method generates a rich set of shape variations by locally combining training samples. We demonstrate the performance of the framework by applying it to both 2-D and 3-D data sets with emphasis on biomedical image segmentation applications.

racing neurons in large-scale microscopy data is crucial to establishing a wiring diagram of the brain, which is needed to understand how neural circuits in the brain process information and generate behavior. Automatic techniques often fail for large and complex datasets, and connectomics researchers may spend weeks or months manually tracing neurons using 2D image stacks. We present a design study of a new virtual reality (VR) system, developed in collaboration with trained neuroanatomists, to trace neurons in microscope scans of the visual cortex of primates. We hypothesize that using consumer-grade VR technology to interact with neurons directly in 3D will help neuroscientists better resolve complex cases and enable them to trace neurons faster and with less physical and mental strain. We discuss both the design process and technical challenges in developing an interactive system to navigate and manipulate terabyte-sized image volumes in VR. Using a number of different datasets, we demonstrate that, compared to widely used commercial software, consumer-grade VR presents a promising alternative for scientists.

Background
Neighbourhood quality has been connected with an array of health issues, but neighbourhood research has been limited by the lack of methods to characterise large geographical areas. This study uses innovative computer vision methods and a new big data source of street view images to automatically characterise neighbourhood built environments.

Methods
A total of 430 000 images were obtained using Google's Street View Image API for Salt Lake City, Chicago and Charleston. Convolutional neural networks were used to create indicators of street greenness, crosswalks and building type. We implemented log Poisson regression models to estimate associations between built environment features and individual prevalence of obesity and diabetes in Salt Lake City, controlling for individual-level and zip code-level predisposing characteristics.

Results
Computer vision models had an accuracy of 86%–93% compared with manual annotations. Charleston had the highest percentage of green streets (79%), while Chicago had the highest percentage of crosswalks (23%) and commercial buildings/apartments (59%). Built environment characteristics were categorised into tertiles, with the highest tertile serving as the referent group. Individuals living in zip codes with the most green streets, crosswalks and commercial buildings/apartments had relative obesity prevalences that were 25%–28% lower and relative diabetes prevalences that were 12%–18% lower than individuals living in zip codes with the least abundance of these neighbourhood features.

Conclusion
Neighbourhood conditions may influence chronic disease outcomes. Google Street View images represent an underused data resource for the construction of built environment features.

Tomosynthesis, i.e. reconstruction of 3D volumes using projections from a limited perspective is a classical inverse, ill-posed or under constrained problem. Data insufficiency leads to reconstruction artifacts that vary in severity depending on the particular problem, the reconstruction method and also on the object being imaged. Machine learning has been used successfully in tomographic problems where data is insufficient, but the challenge with machine learning is that it introduces bias from the learning dataset. A novel framework to improve the quality of the tomosynthesis reconstruction that limits the learning dataset bias by maintaining consistency with the observed data is proposed. Convolutional Neural Networks (CNN) are embedded as regularizers in the reconstruction process to introduce the expected features and characterstics of the likely imaged object. The minimization of the objective function keeps the solution consistent with the observations and limits the bias introduced by the machine learning regularizers, improving the quality of the reconstruction. The proposed method has been developed and studied in the specific problem of Cone Beam Tomosynthesis Flouroscopy (CBT-fluoroscopy)¹ but it is a general framework that can be applied to any image reconstruction problem that is limited by data insufficiency.

Many biomedical image analysis applications require segmentation. Convolutional neural networks (CNN) have become a promising approach to segment biomedical images; however, the accuracy of these methods is highly dependent on the training data. We focus on biomedical image segmentation in the context where there is variation between source and target datasets and ground truth for the target dataset is very limited or non-existent. We use an adversarial based training approach to train CNNs to achieve good accuracy on the target domain. We use the DRIVE and STARE eye vasculture segmentation datasets and show that our approach can significantly improve results where we only use labels of one domain in training and test on the other domain. We also show improvements on membrane detection between MIC-CAI 2016 CREMI challenge and ISBI2013 EM segmentation challenge datasets.

This paper discusses an algorithm for semi-supervised learning to predict cell division and motion in microscopy images. The cells for tracking are detected using extremal region selection and are depicted using a graphical representation. The supervised loss minimizes the error in predictions for the division and move classifiers. The unsupervised loss constrains the incoming links for every detection such that only one of the links is active. Similarly for the outgoing links, we enforce at-most two links to be active. The supervised and un-supervised losses are embedded in a Bayesian framework for probabilistic learning. The classifier predictions are used to model flow variables for every edge in the graph. The cell lineages are solved by formulating it as an energy minimization problem with constraints using integer linear programming. The unsupervised loss adds a significant improvement in the prediction of the division classifier.

While convolutional neural networks (CNN) produce state-of-the-art results in many applications including biomedical image analysis, they are not robust to variability in the data that is not well represented by the training set. An important source of variability in biomedical images is the appearance of objects such as contrast and texture due to different imaging settings. We introduce the neighborhood similarity layer (NSL) which can be used in a CNN to improve robustness to changes in the appearance of objects that are not well represented by the training data. The proposed NSL transforms its input feature map at a given pixel by computing its similarity to the surrounding neighborhood. This transformation is spatially varying, hence not a convolution. It is differentiable; therefore, networks including the proposed layer can be trained in an end-to-end manner. We demonstrate the advantages of the NSL for the vasculature segmentation and cell detection problems.

Objective: Establishing a primate multiscale genetic brain network linking key microstructural brain components to social behavior remains an elusive goal.

Background: Diffusion MRI, which quantifies the magnitude and anisotropy of water diffusion in brain tissues, offers unparalleled opportunity to link the macroconnectome (resolution of ~0.5mm) to histological-based microconnectome at synaptic resolution.

Design/Methods: We tested the hypothesis that the simplest (and most clinically-used) reconstruction technique (known as diffusion tensor imaging, DTI) will yield similar brain connectivity patterns in the visual system (from optic chiasm to visual cortex) compared to more sophisticated and accurate reconstruction methods including diffusion spectrum imaging (DSI), q-ball imaging (QBI), and generalized q-sampling imaging. We obtained high resolution diffusion MRI data on ex vivo brain from Macaca fascicularis: MRI 7T, resolution 0.5 mm isotropic, 515 diffusion volumes up to b-value (aka diffusion sensitivity) of 40,000 s/mm2 with scan time ~100 hrs.

Results: Tractography results show that despite the limited ability of DTI to resolve crossing fibers at the optic chiasm, DTI-based tracts mapped to the known projections of layers in lateral geniculate nucleus and to the primary visual cortex. The other reconstructions were superior in localized regions for resolving crossing regions.

Conclusions: In conclusion, despite its simplifying assumptions, DTI-based fiber tractography can be used to generate accurate brain connectivity maps that conform to established neuroanatomical features in the visual system.

Radiation therapy has presented a need for dynamic tracking of a target tumor volume. Fiducial markers such as implanted gold seeds have been used to gate radiation delivery but the markers are invasive and gating significantly increases treatment time. Pretreatment acquisition of a 4DCT allows for the development of accurate motion estimation for treatment planning. A deep convolutional neural network and subspace motion tracking is used to recover anatomical positions from a single radiograph projection in real-time. We approximate the nonlinear inverse of a diffeomorphic transformation composed with radiographic projection as a deep network that produces subspace coordinates to define the patient-specific deformation of the lungs from a baseline anatomic position. The geometric accuracy of the subspace projections on real patient data is similar to accuracy attained by original image registration between individual respiratory-phase image volumes.

We introduce Flexible Live‐Wire, a generalization of the Live‐Wire interactive segmentation technique with floating anchors. In our approach, the user input for Live‐Wire is no longer limited to the setting of pixel‐level anchor nodes, but can use more general anchor sets. These sets can be of any dimension, size, or connectedness. The generality of the approach allows the design of a number of user interactions while providing the same functionality as the traditional Live‐Wire. In particular, we experiment with this new flexibility by designing four novel Live‐Wire interactions based on specific primitives: paint, pinch, probable, and pick anchors. These interactions are only a subset of the possibilities enabled by our generalization. Moreover, we discuss the computational aspects of this approach and provide practical solutions to alleviate any additional overhead. Finally, we illustrate our approach and new interactions through several example segmentations.

The use of a limited set of signatures in nuclear forensics and nuclear safeguards may reduce the discriminating power for identifying unknown nuclear materials, or for verifying processing at existing facilities. Nuclear proliferomics is a proposed new field of study that advocates for the acquisition of large databases of nuclear material properties from a variety of analytical techniques. As demonstrated on a common uranium trioxide polymorph, α-UO3, in this paper, nuclear proliferomics increases the ability to improve confidence in identifying the processing history of nuclear materials. Specifically, α-UO3 was investigated from the calcination of unwashed uranyl peroxide at 350, 400, 450, 500, and 550 °C in air. Scanning electron microscopy (SEM) images were acquired of the surface morphology, and distinct qualitative differences are presented between unwashed and washed uranyl peroxide, as well as the calcination products from the unwashed uranyl peroxide at the investigated temperatures. Differential scanning calorimetry (DSC), UV–Vis spectrophotometry, powder X-ray diffraction (p-XRD), and thermogravimetric analysis-mass spectrometry (TGA-MS) were used to understand the source of these morphological differences as a function of calcination temperature. Additionally, the SEM images were manually segmented using Morphological Analysis for MAterials (MAMA) software to identify quantifiable differences in morphology for three different surface features present on the unwashed uranyl peroxide calcination products. No single quantifiable signature was sufficient to discern all calcination temperatures with a high degree of confidence; therefore, advanced statistical analysis was performed to allow the combination of a number of quantitative signatures, with their associated uncertainties, to allow for complete discernment by calcination history. Furthermore, machine learning was applied to the acquired SEM images to demonstrate automated discernment with at least 89% accuracy.

Modern science is inundated with ever increasing data sizes as computational capabilities and image acquisition techniques continue to improve. For example, simulations are tackling ever larger domains with higher fidelity, and high-throughput microscopy techniques generate larger data that are fundamental to gather biologically and medically relevant insights. As the image sizes exceed memory, and even sometimes local disk space, each step in a scientific workflow is impacted. Current software solutions enable data exploration with limited interactivity for visualization and analytic tasks. Furthermore analysis on HPC systems often require complex hand-written parallel implementations of algorithms that suffer from poor portability and maintainability. We present a software infrastructure that simplifies end-to-end visualization and analysis of massive data. First, a hierarchical streaming data access layer enables interactive exploration of remote data, with fast data fetching to test analytics on subsets of the data. Second, a library simplifies the process of developing new analytics algorithms, allowing users to rapidly prototype new approaches and deploy them in an HPC setting. Third, a scalable runtime system automates mapping analysis algorithms to whatever computational hardware is available, reducing the complexity of developing scaling algorithms. We demonstrate the usability and performance of our system using a use case from neuroscience: filtering, registration, and visualization of tera-scale microscopy data. We evaluate the performance of our system using a leadership-class supercomputer, Shaheen II.

The brain undergoes rapid development during early childhood as a series of biophysical and chemical processes occur, which can be observed in magnetic resonance (MR) images as a change over time of white matter intensity relative to gray matter. Such a contrast change manifests in specific patterns in different imaging modalities, suggesting that brain maturation is encoded by appearance changes in multi-modal MRI. In this paper, we explore the patterns of early brain growth encoded by multi-modal contrast changes in a longitudinal study of children. For a given modality, contrast is measured by comparing histograms of intensity distributions between white and gray matter. Multivariate non-linear mixed effects (NLME) modeling provides subject-specific as well as population growth trajectories which accounts for contrast from multiple modalities. The multivariate NLME procedure and resulting non-linear contrast functions enable the study of maturation in various regions of interest. Our analysis of several brain regions in a study of 70 healthy children reveals a posterior to anterior pattern of timing of maturation in the major lobes of the cerebral cortex, with posterior regions maturing earlier than anterior regions. Furthermore, we find significant differences between maturation rates between males and females.

Background
Restricted and repetitive behaviors are defining features of autism spectrum disorder (ASD). Under revised diagnostic criteria for ASD, this behavioral domain now includes atypical responses to sensory stimuli. To date, little is known about the neural circuitry underlying these features of ASD early in life.

Methods
Longitudinal diffusion tensor imaging data were collected from 217 infants at high familial risk for ASD. Forty-four of these infants were diagnosed with ASD at age 2. Targeted cortical, cerebellar, and striatal white matter pathways were defined and measured at ages 6, 12, and 24 months. Dependent variables included the Repetitive Behavior Scale-Revised and the Sensory Experiences Questionnaire.

Results
Among children diagnosed with ASD, repetitive behaviors and sensory response patterns were strongly correlated, even when accounting for developmental level or social impairment. Longitudinal analyses indicated that the genu and cerebellar pathways were significantly associated with both repetitive behaviors and sensory responsiveness but not social deficits. At age 6 months, fractional anisotropy in the genu significantly predicted repetitive behaviors and sensory responsiveness at age 2. Cerebellar pathways significantly predicted later sensory responsiveness. Exploratory analyses suggested a possible disordinal interaction based on diagnostic status for the association between fractional anisotropy and repetitive behavior.

Conclusions
Our findings suggest that restricted and repetitive behaviors contributing to a diagnosis of ASD at age 2 years are associated with structural properties of callosal and cerebellar white matter pathways measured during infancy and toddlerhood. We further identified that repetitive behaviors and unusual sensory response patterns co-occur and share common brain-behavior relationships. These results were strikingly specific given the absence of association between targeted pathways and social deficits.