SCIENTIFIC COMPUTING AND IMAGING INSTITUTE
at the University of Utah

Complex systems are often described with competing models. Such divergence of interpretation on the system may stem from model fidelity, mathematical simplicity, and more generally, our limited knowledge of the underlying processes. Meanwhile, available but limited observations of system state could further complicates one's prediction choices. Over the years, data assimilation techniques, such as the Kalman filter, have become essential tools for improved system estimation by incorporating both models forecast and measurement; but its potential to mitigate the impacts of aforementioned model-form uncertainty has yet to be developed. Based on an earlier study of Multi-model Kalman filter, we propose a novel framework to assimilate multiple models with observation data for nonlinear systems, using extended Kalman filter, ensemble Kalman filter and particle filter, respectively. Through numerical examples of subsurface flow, we demonstrate that the new assimilation framework provides an effective and improved forecast of system behaviour.

Introduction
Myocardial ischemia is a pathological condition initiated by supply and demand imbalance of the blood to the heart. Previous studies suggest that ischemia originates in the subendocardium, i.e., that nontransmural ischemia is limited to the subendocardium. By contrast, we hypothesized that acute myocardial ischemia is not limited to the subendocardium and sought to document its spatial distribution in an animal preparation. The goal of these experiments was to investigate the spatial organization of ischemia and its relationship to the resulting shifts in ST segment potentials during short episodes of acute ischemia.

Methods
We conducted acute ischemia studies in open-chest canines (N = 19) and swines (N = 10), which entailed creating carefully controlled ischemia using demand, supply or complete occlusion ischemia protocols and recording intramyocardial and epicardial potentials. Elevation of the potentials at 40% of the ST segment between the J-point and the peak of the T-wave (ST40%) provided the metric for local ischemia. The threshold for ischemic ST segment elevations was defined as two standard deviations away from the baseline values.

Results
The relative frequency of occurrence of acute ischemia was higher in the subendocardium (78% for canines and 94% for swines) and the mid-wall (87% for canines and 97% for swines) in comparison with the subepicardium (30% for canines and 22% for swines). In addition, acute ischemia was seen arising throughout the myocardium (distributed pattern) in 87% of the canine and 94% of the swine episodes. Alternately, acute ischemia was seen originating only in the subendocardium (subendocardial pattern) in 13% of the canine episodes and 6% of the swine episodes (p < 0.05).

Conclusions
Our findings suggest that the spatial distribution of acute ischemia is a complex phenomenon arising throughout the myocardial wall and is not limited to the subendocardium.

The proximal femur is abnormally shaped in patients with cam-type femoroacetabular impingement (FAI). Impingement
may elicit bone remodeling at the proximal femur, causing increases in cortical bone thickness. We used correspondence-based shape modeling to quantify and compare cortical thickness between cam patients and controls for the location of the cam lesion and the proximal femur. Computed tomography images were segmented for 45 controls and 28 cam-type FAI patients. The segmentations were input to a correspondence-based shape model to identify the region of the cam lesion. Median cortical thickness data over the region of the cam lesion and the proximal femur were compared between mixed-gender and gender-specific groups. Median [interquartile range] thickness was significantly greater in FAI patients than controls in the cam lesion (1.47 [0.64] vs. 1.13 [0.22] mm, respectively; p < 0.001) and proximal femur (1.28 [0.30] vs. 0.97 [0.22] mm, respectively; p < 0.001). Maximum thickness in the region of the cam lesion was more anterior and less lateral (p < 0.001) in FAI patients. Male FAI patients had increased thickness compared to male controls in the cam lesion (1.47 [0.72] vs. 1.10 [0.19] mm, respectively; p < 0.001) and proximal femur (1.25 [0.29] vs. 0.94 [0.17] mm, respectively; p < 0.001). Thickness was not significantly different between male and female controls. Clinical significance: Studies of non-pathologic cadavers have provided guidelines regarding safe surgical resection depth for FAI patients. However, our results suggest impingement induces cortical thickening in cam patients, which may strengthen the proximal femur. Thus, these previously established guidelines may be too conservative.

The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients.

The recent precipitous losses of summer Arctic sea ice have outpaced the projections of most climate models. A number of efforts to improve these models have focused in part on a more accurate accounting of sea ice albedo or reflectance. In late spring and summer, the albedo of the ice pack is determined primarily by melt ponds that form on the sea ice surface. The transition of pond configurations from isolated structures to interconnected networks is critical in allowing the lateral flow of melt water toward drainage features such as large brine channels, fractures, and seal holes, which can alter the albedo by removing the melt water. Moreover, highly connected ponds can influence the formation of fractures and leads during ice break-up. Here we develop algorithmic techniques for mapping photographic images of melt ponds onto discrete conductance networks which represent the geometry and connectedness of pond configurations. The effective conductivity of the networks is computed to approximate the ease of lateral flow. We implement an image processing algorithm with mathematical morphology operations to produce a conductance matrix representation of the melt ponds. Basic clustering and edge elimination, using undirected graphs, are then used to map the melt pond connections and reduce the conductance matrix to include only direct connections. The results for images taken during different times of the year are visually inspected and the number of mislabels is used to evaluate performance.

The Deflagration to Detonation Transition (DDT) in large arrays (100s) of explosive devices is investigated using large-scale computer simulations running the Uintah Computational Framework. Our particular interest is understanding the fundamental physical mechanisms by which convective deflagration of cylindrical PBX 9501 devices can transition to a fully-developed detonation in transportation accidents. The simulations reveal two dominant mechanisms, inertial confinement and Impact to Detonation Transition. In this study we examined the role of physical spacing of the cylinders and how it influenced the initiation of DDT.

The detonation of hundreds of explosive devices from either a transportation or storage accident is an extremely dangerous event. This paper focuses on identifying ways of packing/storing arrays of explosive cylinders that will reduce the probability of a Deflagration to Detonation Transition (DDT). The Uintah Computational Framework was utilized to predict the conditions necessary for a large scale DDT to occur. The results showed that the arrangement of the explosive cylinders and the number of devices packed in a "box" greatly effects the probability of a detonation.

The Uintah framework for solving a broad class of fluid-structure interaction problems uses a layered taskgraph approach that decouples the problem specification as a set of tasks from the adaptove runtime system that executes these tasks. Uintah has been developed by using a problem-driven approach that dates back to its inception. Using this approach it is possible to improve the performance of the problem-independent software components to enable the solution of broad classes of problems as well as the driving problem itself. This process is illustrated by a motivating problem that is the computational modeling of the hazards posed by thousands of explosive devices during a Deflagration to Detonation Transition (DDT) that occurred on Highway 6 in Utah. In order to solve this complex fluid-structure interaction problem at the required scale, algorithmic and data structure improvements were needed in a code that already appeared to work well at scale. These transformations enabled scalable runs for our target problem and provided the capability to model the transition to detonation. The performance improvements achieved are shown and the solution to the target problem provides insight as to why the detonation happened, as well as to a possible remediation strategy.

Visualization practitioners are constantly developing new, innovative ways to visualize data, but much of the software that practitioners produce does not make it into production in professional systems. To solve this problem, we have developed and informally tested two open source systems. The first, Candela, is a framework and API for creating visualization components for the web that can wrap up new or existing visualizations as needed. Because Candela's API generalizes the inputs to a visualization, we have also developed a system called Resonant Laboratory that makes it possible for novice users to connect arbitrary datasets to Candela visualizations. Together, these systems enable novice users to explore and share their data with the growing library of state-of-the-art visualization techniques.

As our ability to generate large and complex datasets grows, accessing and processing these massive data collections is increasingly the primary bottleneck in scientific analysis. Challenges include retrieving, converting, resampling, and combining remote and often disparately located data ensembles with only limited support from existing tools. In particular, existing solutions rely predominantly on extensive data transfers or large-scale remote computing resources, both of which are inherently offline processes with long delays and substantial repercussions for any mistakes. Such workflows severely limit the flexible exploration and rapid evaluation of new hypotheses that are crucial to the scientific process and thereby impede scientific discovery. Here we present an embedded domain-specific language (EDSL) specifically designed for the interactive exploration of largescale, remote data. Our EDSL allows users to express a wide range of data analysis operations in a simple and abstract manner. The underlying runtime system transparently resolves issues such as remote data access and resampling while at the same time maintaining interactivity through progressive and interruptible computation. This system enables, for the first time, interactive remote exploration of massive datasets such as the 7km NASA GEOS-5 Nature Run simulation, which previously have been analyzed only offline or at reduced resolution.

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual Deep Brain Stimulation Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson’s disease, essential tremor, Alzheimer’s disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year’s international Think Tank, with a view toward current and near future advancement of the field.

Diffusion-weighted (DW) MRI has become a widely adopted imaging modality to reveal the underlying brain connectivity. Long acquisition times and/or non-cooperative patients increase the chances of motion-related artifacts. Whereas slow bulk motion results in inter-gradient misalignment which can be handled via retrospective motion correction algorithms, fast bulk motion usually affects data during the application of a single diffusion gradient causing signal dropout artifacts. Common practices opt to discard gradients bearing signal attenuation due to the difficulty of their retrospective correction, with the disadvantage to lose full gradients for further processing. Nonetheless, such attenuation might only affect limited number of slices within a gradient volume. Q-space resampling has recently been proposed to recover corrupted slices while saving gradients for subsequent reconstruction. However, few corrupted gradients are implicitly assumed which might not hold in case of scanning unsedated infants or patients in pain. In this paper, we propose to adopt recent advances in compressive sensing based reconstruction of the diffusion orientation distribution functions (ODF) with under sampled measurements to resample corrupted slices. We make use of Simple Harmonic Oscillator based Reconstruction and Estimation (SHORE) basis functions which can analytically model ODF from arbitrary sampled signals. We demonstrate the impact of the proposed resampling strategy compared to state-of-art resampling and gradient exclusion on simulated intra-gradient motion as well as samples from real DWI data.

Probabilistic label maps are a useful tool for important medical image analysis tasks such as segmentation, shape analysis, and atlas building. Existing methods typically rely on blurred signed distance maps or smoothed label maps to model uncertainties and shape variabilities, which do not conform to any generative model or estimation process, and are therefore suboptimal. In this paper, we propose to learn probabilistic label maps using a generative model on given set of binary label maps. The proposed approach generalizes well on unseen data while simultaneously capturing the variability in the training samples. Efficiency of the proposed approach is demonstrated for consensus generation and shape-based clustering using synthetic datasets as well as left atrial segmentations from late-gadolinium enhancement MRI.

Can people use text-entry based brain-computer interface (BCI) systems and start a free spelling mode without any calibration session? Brain activities differ largely across people and across sessions for the same user. Thus, how can the text-entry system classify the desired character among the other characters in the P300-based BCI speller matrix? In this paper, we introduce a new unsupervised classifier for a P300-based BCI speller, which uses a disjunctive normal form representation to define an energy function involving a logistic sigmoid function for classification. Our proposed classifier updates the initialized random weights performing classification for the P300 signals from the recorded data exploiting the knowledge of the sequence of row/column highlights. To verify the effectiveness of the proposed method, we performed an experimental analysis on data from 7 healthy subjects, collected in our laboratory. We compare the proposed unsupervised method to a baseline supervised linear discriminant analysis (LDA) classifier and demonstrate its effectiveness.

Segmenting images of low quality or with missing data is a challenging problem. Integrating statistical prior information about the shapes to be segmented can improve the segmentation results significantly. Most shape-based segmentation algorithms optimize an energy functional and find a point estimate for the object to be segmented. This does not provide a measure of the degree of confidence in that result, neither does it provide a picture of other probable solutions based on the data and the priors. With a statistical view, addressing these issues would involve the problem of characterizing the posterior densities of the shapes of the objects to be segmented. For such characterization, we propose a Markov chain Monte Carlo (MCMC) sampling-based image segmentation algorithm that uses statistical shape priors. In addition to better characterization of the statistical structure of the problem, such an approach would also have the potential to address issues with getting stuck at local optima, suffered by existing shape-based segmentation methods. Our approach is able to characterize the posterior probability density in the space of shapes through its samples, and to return multiple solutions, potentially from different modes of a multimodal probability density, which would be encountered, e.g., in segmenting objects from multiple shape classes. We present promising results on a variety of data sets. We also provide an extension for segmenting shapes of objects with parts that can go through independent shape variations. This extension involves the use of local shape priors on object parts and provides robustness to limitations in shape training data size.

Multimodal shape density estimation is a challenging task in many biomedical image segmentation problems. Existing techniques in the literature estimate the underlying shape distribution by extending Parzen density estimator to the space of shapes. Such density estimates are only expressed in terms of distances between shapes which may not be sufficient for ensuring accurate segmentation when the observed intensities provide very little information about the object boundaries. In such scenarios, employing additional shape-dependent discriminative features as priors and exploiting both shape and feature priors can aid to the segmentation process. In this paper, we propose a segmentation algorithm that uses nonparametric joint shape and feature priors using Parzen density estimator. The joint prior density estimate is expressed in terms of distances between shapes and distances between features. We incorporate the learned joint shape and feature prior distribution into a maximum a posteriori estimation framework for segmentation. The resulting optimization problem is solved using active contours. We present experimental results on dendritic spine segmentation in 2-photon microscopy images which involve a multimodal shape density.

This paper addresses the challenge of extracting meaningful information from measured bioelectric signals generated by complex, large scale physiological systems such as the brain or the heart. We focus on a combination of the well-known Laplacian eigenmaps machine learning approach with dynamical systems ideas to analyze emergent dynamic behaviors. The method reconstructs the abstract dynamical system phase-space geometry of the embedded measurements and tracks changes in physiological conditions or activities through changes in that geometry. It is geared to extract information from the joint behavior of time traces obtained from large sensor arrays, such as those used in multiple-electrode ECG and EEG, and explore the geometrical structure of the low dimensional embedding of moving time windows of those joint snapshots. Our main contribution is a method for mapping vectors from the phase space to the data domain. We present cases to evaluate the methods, including a synthetic example using the chaotic Lorenz system, several sets of cardiac measurements from both canine and human hearts, and measurements from a human brain.

Reconstruction of the electrical sources of human EEG activity at high spatio-temporal accuracy is an important aim in neuroscience and neurological diagnostics. Over the last decades, numerous studies have demonstrated that realistic modeling of head anatomy improves the accuracy of source reconstruction of EEG signals. For example, including a cerebro-spinal fluid compartment and the anisotropy of white matter electrical conductivity were both shown to significantly reduce modeling errors. Here, we for the first time quantify the role of detailed reconstructions of the cerebral blood vessels in volume conductor head modeling for EEG. To study the role of the highly arborized cerebral blood vessels, we created a submillimeter head model based on ultra-high-field-strength (7T) structural MRI datasets. Blood vessels (arteries and emissary/intraosseous veins) were segmented using Frangi multi-scale vesselness filtering. The final head model consisted of a geometry-adapted cubic mesh with over 17×10(6) nodes. We solved the forward model using a finite-element-method (FEM) transfer matrix approach, which allowed reducing computation times substantially and quantified the importance of the blood vessel compartment by computing forward and inverse errors resulting from ignoring the blood vessels. Our results show that ignoring emissary veins piercing the skull leads to focal localization errors of approx. 5 to 15mm. Large errors (>2cm) were observed due to the carotid arteries and the dense arterial vasculature in areas such as in the insula or in the medial temporal lobe. Thus, in such predisposed areas, errors caused by neglecting blood vessels can reach similar magnitudes as those previously reported for neglecting white matter anisotropy, the CSF or the dura - structures which are generally considered important components of realistic EEG head models. Our findings thus imply that including a realistic blood vessel compartment in EEG head models will be helpful to improve the accuracy of EEG source analyses particularly when high accuracies in brain areas with dense vasculature are required.

Background
Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision.

Methods
We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology.

Results
The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions.

Conclusion
rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way.