SCI Publications

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.

Functional properties of neurons are strongly coupled with their morphology. Changes in neuronal activity alter morphological characteristics of dendritic spines. First step towards understanding the structure-function relationship is to group spines into main spine classes reported in the literature. Shape analysis of dendritic spines can help neuroscientists understand the underlying relationships. Due to unavailability of reliable automated tools, this  analysis is currently performed manually which is a time-intensive and subjective task. Several studies on spine shape classification have been reported in the literature, however, there is an on-going debate on whether distinct spine shape classes exist or whether spines should be modeled through a continuum of shape variations. Another challenge is the subjectivity and bias that is introduced due to the supervised nature of classification approaches. In this paper, we aim to address these issues by presenting a clustering perspective. In this context, clustering may serve both confirmation of known patterns and discovery of new ones. We perform cluster analysis on two-photon microscopic images of spines using morphological, shape, and appearance based features and gain insights into the spine  shape analysis problem. We use histogram of oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological features, and intensity profile based features for cluster analysis. We use x-means to perform cluster analysis that selects the number of clusters automatically using the Bayesian information criterion (BIC). For all features, this analysis produces 4 clusters and we observe the formation of at least one cluster consisting of spines which are difficult to be assigned to a known class. This observation supports the argument of intermediate shape types.

Dendritic spines are one of the key functional components of neurons. Their morphological changes are correlated with neuronal activity. Neuroscientists study spine shape variations to understand their relation with neuronal activity. Currently this analysis performed manually, the availability of reliable automated tools would assist neuroscientists and accelerate this research. Previously, morphological features based spine analysis has been performed and reported in the literature. In this paper, we explore the idea of using and comparing manifold learning techniques for classifying spine shapes. We start with automatically segmented data and construct our feature vector by stacking and concatenating the columns of images. Further, we apply unsupervised manifold learning algorithms and compare their performance in the context of dendritic spine classification. We achieved 85.95% accuracy on a dataset of 242 automatically segmented mushroom and stubby spines. We also observed that ISOMAP implicitly computes prominent features suitable for classification purposes.

Analysis of dendritic spines is an essential task to understand the functional behavior of neurons. Their shape variations are known to be closely linked with neuronal activities. Spine shape analysis in particular, can assist neuroscientists to identify this relationship. A novel shape representation has been proposed recently, called Disjunctive Normal Shape Models (DNSM). DNSM is a parametric shape representation and has proven to be successful in several segmentation problems. In this paper, we apply this parametric shape representation as a feature extraction algorithm. Further, we propose a kernel density estimation (KDE) based classification approach for dendritic spine classification. We evaluate our proposed approach on a data set of 242 spines, and observe that it outperforms the classical morphological feature based approach for spine classification. Our probabilistic framework also provides a way to examine the separability of spine shape classes in the likelihood ratio space, which leads to further insights about the nature of the shape analysis problem in this context.

The primary goal of visual data exploration tools is to enable the discovery of new insights. To justify and reproduce insights, the discovery process needs to be documented and communicated. A common approach to documenting and presenting findings is to capture visualizations as images or videos. Images, however, are insufficient for telling the story of a visual discovery, as they lack full provenance information and context. Videos are difficult to produce and edit, particularly due to the non-linear nature of the exploratory process. Most importantly, however, neither approach provides the opportunity to return to any point in the exploration in order to review the state of the visualization in detail or to conduct additional analyses. In this paper we present CLUE (Capture, Label, Understand, Explain), a model that tightly integrates data exploration and presentation of discoveries. Based on provenance data captured during the exploration process, users can extract key steps, add annotations, and author "Vistories", visual stories based on the history of the exploration. These Vistories can be shared for others to view, but also to retrace and extend the original analysis. We discuss how the CLUE approach can be integrated into visualization tools and provide a prototype implementation. Finally, we demonstrate the general applicability of the model in two usage scenarios: a Gapminder-inspired visualization to explore public health data and an example from molecular biology that illustrates how Vistories could be used in scientific journals.

The material point method (MPM) has been very successful in providing solutions to many challenging problems involving large deformations. Nevertheless there are some important issues that remain to be resolved with regard to its analysis. One key challenge applies to both MPM and particle-in-cell (PIC) methods and arises from the difference between the number of particles and the number of the nodal grid points to which the particles are mapped. This difference between the number of particles and the number of grid points gives rise to a non-trivial null space of the linear operator that maps particle values onto nodal grid point values. In other words, there are non-zero particle values that when mapped to the grid point nodes result in a zero value there. Moreover, when the nodal values at the grid points are mapped back to particles, part of those particle values may be in that same null space. Given positive mapping weights from particles to nodes such null space values are oscillatory in nature. While this problem has been observed almost since the beginning of PIC methods there are still elements of it that are problematical today as well as methods that transcend it. The null space may be viewed as being connected to the ringing instability identified by Brackbill for PIC methods. It will be shown that it is possible to remove these null space values from the solution using a null space filter. This filter improves the accuracy of the MPM methods using an approach that is based upon a local singular value decomposition (SVD) calculation. This local SVD approach is compared against the global SVD approach previously considered by the authors and to a recent MPM method by Zhang and colleagues.

Algorithms for sort-last parallel volume rendering on large distributed memory machines usually divide a dataset equally across all nodes for rendering. Depending on the features that a user wants to see in a dataset, all the nodes will rarely finish rendering at the same time. Existing compositing algorithms do not often take this into consideration, which can lead to significant delays when nodes that are compositing wait for other nodes that are still rendering. In this paper, we present an image compositing algorithm that uses spatial and temporal awareness to dynamically schedule the exchange of regions in an image and progressively composite images as they become available. Running on the Edison supercomputer at NERSC, we show that a scheduler-based algorithm with awareness of the spatial contribution from each rendering node can outperform traditional image compositing algorithms.

Modern supercomputers have thousands of nodes, each with CPUs and/or GPUs capable of several teraflops. However, the network connecting these nodes is relatively slow, on the order of gigabits per second. For time-critical workloads such as interactive visualization, the bottleneck is no longer computation but communication. In this paper, we present an image compositing algorithm that works on both CPU-only and GPU-accelerated supercomputers and focuses on communication avoidance and overlapping communication with computation at the expense of evenly balancing the workload. The algorithm has three stages: a parallel direct send stage, followed by a tree compositing stage and a gather stage. We compare our algorithm with radix-k and binary-swap from the IceT library in a hybrid OpenMP/MPI setting on the Stampede and Edison supercomputers, show strong scaling results and explain how we generally achieve better performance than these two algorithms. We developed a GPU-based image compositing algorithm where we use CUDA kernels for computation and GPU Direct RDMA for inter-node GPU communication. We tested the algorithm on the Piz Daint GPU-accelerated supercomputer and show that we achieve performance on par with CPUs. Lastly, we introduce a workflow in which both rendering and compositing are done on the GPU.

OBJECTIVE:
Transcranial direct current stimulation (tDCS) aims to alter brain function non-invasively via electrodes placed on the scalp. Conventional tDCS uses two relatively large patch electrodes to deliver electrical current to the brain region of interest (ROI). Recent studies have shown that using dense arrays containing up to 512 smaller electrodes may increase the precision of targeting ROIs. However, this creates a need for methods to determine effective and safe stimulus patterns as the number of degrees of freedom is much higher with such arrays. Several approaches to this problem have appeared in the literature. In this paper, we describe a new method for calculating optimal electrode stimulus patterns for targeted and directional modulation in dense array tDCS which differs in some important aspects with methods reported to date.

APPROACH:
We optimize stimulus pattern of dense arrays with fixed electrode placement to maximize the current density in a particular direction in the ROI. We impose a flexible set of safety constraints on the current power in the brain, individual electrode currents, and total injected current, to protect subject safety. The proposed optimization problem is convex and thus efficiently solved using existing optimization software to find unique and globally optimal electrode stimulus patterns.

MAIN RESULTS:
Solutions for four anatomical ROIs based on a realistic head model are shown as exemplary results. To illustrate the differences between our approach and previously introduced methods, we compare our method with two of the other leading methods in the literature. We also report on extensive simulations that show the effect of the values chosen for each proposed safety constraint bound on the optimized stimulus patterns.

SIGNIFICANCE:
The proposed optimization approach employs volume based ROIs, easily adapts to different sets of safety constraints, and takes negligible time to compute. An in-depth comparison study gives insight into the relationship between different objective criteria and optimized stimulus patterns. In addition, the analysis of the interaction between optimized stimulus patterns and safety constraint bounds suggests that more precise current localization in the ROI, with improved safety criterion, may be achieved by careful selection of the constraint bounds.

We have created the Neurostimulation Uncertainty Viewer (nuView or nView) tool for exploring data arising from deep brain stimulation (DBS). Simulated volume of tissue activated (VTA), using clinical electrode placements, are recorded along withpatient outcomes in the Unified Parkinson's disease rating scale (UPDRS). The data is volumetric and sparse, with multi-value patient results for each activated voxel in the simulation. nView provides a collection of visual methods to explore the activated tissue to enhance understanding of electrode usage for improved therapy with DBS.

Modeling thermal radiation is computationally challenging in parallel due to its all-to-all physical and resulting computational connectivity, and is also the dominant mode of heat transfer in practical applications such as next-generation clean coal boilers, being modeled by the Uintah framework. However, a direct all-to-all treatment of radiation is prohibitively expensive on large computers systems whether homogeneous or heterogeneous. DOE Titan and the planned DOE Summit and Sierra machines are examples of current and emerging GPUbased heterogeneous systems where the increased processing capability of GPUs over CPUs exacerbates this problem. These systems require that computational frameworks like Uintah leverage an arbitrary number of on-node GPUs, while simultaneously utilizing thousands of GPUs within a single simulation. We show that radiative heat transfer problems can be made to scale within Uintah on heterogeneous systems through a combination of reverse Monte Carlo ray tracing (RMCRT) techniques combined with AMR, to reduce the amount of global communication. In particular, significant Uintah infrastructure changes, including a novel lock and contention-free, thread-scalable data structure for managing MPI communication requests and improved memory allocation strategies were necessary to achieve excellent strong scaling results to 16384 GPUs on Titan.