G. S. Smith, K. A. Mills, G. M. Pontone, W. S. Anderson, K. M. Perepezko, J. Brasic, Y. Zhou, J. Brandt, C. R. Butson, D. P. Holt, W. B. Mathews, R. F. Dannals, D. F. Wong, Z. Mari. Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease, In Parkinsonism and Related Disorders, Elsevier, 2019.
Deep brain stimulation (DBS) is an established treatment Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of STN DBS in PD on the dopamine system and neural circuitry employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease striatal VMAT2, secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical metabolism.
Q. Tran, M. Berzins, W. Solowski. An improved moving least squares method for the Material Point Method, In Proceedings of the 2nd International Conference on the Material Point Method for Modelling Soil-Water-Structure Interaction (MPM 2019), 2019.
The paper presents an improved moving least squares reconstruction technique for the Material Point Method. The moving least squares reconstruction(MLS)can improve spatial accuracy in simulations involving large deformations. However, the MLS algorithm relies on computing the inverse of the moment matrix.This is both expensive and potentially unstable when there are not enough material points to reconstruct the high-order least squares function, which leads to a singular or an ill-conditioned matrix. The shown formulation can overcome this limitation while retain the same order of accuracy compared with the conventional moving least squares reconstruction.Numerical experiments demonstrate the improvements in the accuracy and comparison with the original Material Point Method and the Convected Particles Domain Interpolation method.
Q. A. Tran, W. Sołowski, M. Berzins, J. Guilkey. A convected particle least square interpolation material point method, In International Journal for Numerical Methods in Engineering, Wiley, October, 2019.
Applying the convected particle domain interpolation (CPDI) to the material point method has many advantages over the original material point method, including significantly improved accuracy. However, in the large deformation regime, the CPDI still may not retain the expected convergence rate. The paper proposes an enhanced CPDI formulation based on least square reconstruction technique. The convected particle least square interpolation (CPLS) material point method assumes the velocity field inside the material point domain as nonconstant. This velocity field in the material point domain is mapped to the background grid nodes with a moving least squares reconstruction. In this paper, we apply the improved moving least squares method to avoid the instability of the conventional moving least squares method due to a singular matrix. The proposed algorithm can improve convergence rate, as illustrated by numerical examples using the method of manufactured solutions.
W. Usher, I. Wald, J. Amstutz, J. Gunther, C. Brownlee, V. Pascucci. Scalable Ray Tracing Using the Distributed FrameBuffer, In Eurographics Conference on Visualization (EuroVis) 2019, Vol. 38, No. 3, 2019.
Image- and data-parallel rendering across multiple nodes on high-performance computing systems is widely used in visualization to provide higher frame rates, support large data sets, and render data in situ. Specifically for in situ visualization, reducing bottlenecks incurred by the visualization and compositing is of key concern to reduce the overall simulation runtime. Moreover, prior algorithms have been designed to support either image- or data-parallel rendering and impose restrictions on the data distribution, requiring different implementations for each configuration. In this paper, we introduce the Distributed FrameBuffer, an asynchronous image-processing framework for multi-node rendering. We demonstrate that our approach achieves performance superior to the state of the art for common use cases, while providing the flexibility to support a wide range of parallel rendering algorithms and data distributions. By building on this framework, we extend the open-source ray tracing library OSPRay with a data-distributed API, enabling its use in data-distributed and in situ visualization applications.
A Retrospective Evaluation of Automated Optimization of Deep Brain Stimulation Settings, In Brain Stimulation, Vol. 12, No. 2, Elsevier, pp. e54--e55. March, 2019.
Influence of head tissue conductivity uncertainties on EEG dipole reconstruction, In Frontiers in Neuroscience, 2019.
Reliable EEG source analysis depends on sufficiently detailed and accurate head models. In this study, we investigate how uncertainties inherent to the experimentally determined conductivity values of the different conductive compartments influence the results of EEG source analysis. In a single source scenario, the superficial and focal somatosensory P20/N20 component, we analyze the influence of varying conductivities on dipole reconstructions using a generalized polynomial chaos (gPC) approach. We find that in particular the conductivity uncertainties for skin and skull have a significant influence on the EEG inverse solution, leading to variations in source localization by several centimeters. The conductivity uncertainties for gray and white matter were found to have little influence on the source localization, but a strong influence on the strength and orientation of the reconstructed source, respectively. As the CSF conductivity is most accurately determined of all conductivities in a realistic head model, CSF conductivity uncertainties had a negligible influence on the source reconstruction. This small uncertainty is a further benefit of distinguishing the CSF in realistic volume conductor models.
Objective: We performed a retrospective analysis of an optimization algorithm for the computation of patient-specific multipolar stimulation configurations employing multiple independent current/voltage sources. We evaluated whether the obtained stimulation configurations align with clinical data and whether the optimized stimulation configurations have the potential to lead to an equal or better stimulation of the target region as manual programming, while reducing the time required for programming sessions. Methods: For three patients (five electrodes) diagnosed with essential tremor, we derived optimized multipolar stimulation configurations using an approach that is suitable for the application in clinical practice. To evaluate the automatically derived stimulation settings, we compared them to the results of the monopolar review. Results: We observe a good agreement between the findings of the monopolar review and the optimized stimulation configurations, with the algorithm assigning the maximal voltage in the optimized multipolar pattern to the contact that was found to lead to the best therapeutic effect in the clinical monopolar review in all cases. Additionally, our simulation results predict that the optimized stimulation settings lead to the activation of an equal or larger volume fraction of the target compared to the manually determined settings in all cases. Conclusions: Our results demonstrate the feasibility of an automatic determination of optimal DBS configurations and motivate a further evaluation of the applied optimization algorithm.
Interactive computation and visualization of deep brain stimulation effects using Duality, In Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, Taylor & Francis, 2019.J. Vorwerk, D. McCann, J. Krüger, C.R. Butson.
Deep brain stimulation (DBS) is an established treatment for movement disorders such as Parkinson’s disease or essential tremor. Currently, the selection of optimal stimulation settings is performed by iteratively adjusting the stimulation parameters and is a time consuming procedure that requires multiple clinic visits of several hours. Recently, computational models to predict and visualize the effect of DBS have been developed with the goal to simplify and accelerate this procedure by providing visual guidance and such models have been made available also on mobile devices. However, currently available visualization software still either lacks mobility, i.e. it is running on desktop computers and no easily available in clinical praxis, or flexibility, as the simulations that are visualized on mobile devices have to be precomputed. The goal of the pipeline presented in this paper is to close this gap: Using Duality, a newly developed software for the interactive visualization of simulation results, we implemented a pipeline that allows to compute DBS simulations in near-real time and instantaneously visualize the result on a tablet computer. We carry out a performance analysis and present the results of a case study in which the pipeline was applied.
Adaptive mesh refinement (AMR) is a key technology for large-scale simulations that allows for adaptively changing the simulation mesh resolution, resulting in significant computational and storage savings. However, visualizing such AMR data poses a significant challenge due to the difficulties introduced by the hierarchical representation when reconstructing continuous field values. In this paper, we detail a comprehensive solution for interactive isosurface rendering of block-structured AMR data. We contribute a novel reconstruction strategy—the octant method—which is continuous, adaptive and simple to implement. Furthermore, we present a generally applicable hybrid implicit isosurface ray-tracing method, which provides better rendering quality and performance than the built-in sampling-based approach in OSPRay. Finally, we integrate our octant method and hybrid isosurface geometry into OSPRay as a module, providing the ability to create high-quality interactive visualizations combining volume and isosurface representations of BS-AMR data. We evaluate the rendering performance, memory consumption and quality of our method on two gigascale block-structured AMR datasets.
A. Warner, J. Tate, B. Burton,, C.R. Johnson.
A High-Resolution Head and Brain Computer Model for Forward and Inverse EEG Simulation, In bioRxiv, Cold Spring Harbor Laboratory, Feb, 2019.
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.
L. Zhou, D. Weiskopf, C. R. Johnson.
Perceptually guided contrast enhancement based on viewing distance, In Journal of Computer Languages, Vol. 55, Elsevier, pp. 100911. 2019.
We propose an image-space contrast enhancement method for color-encoded visualization. The contrast of an image is enhanced through a perceptually guided approach that interfaces with the user with a single and intuitive parameter of the virtual viewing distance. To this end, we analyze a multiscale contrast model of the input image and test the visibility of bandpass images of all scales at a virtual viewing distance. By adapting weights of bandpass images with a threshold model of spatial vision, this image-based method enhances contrast to compensate for contrast loss caused by viewing the image at a certain distance. Relevant features in the color image can be further emphasized by the user using overcompensation. The weights can be assigned with a simple band-based approach, or with an efficient pixel-based approach that reduces ringing artifacts. The method is efficient and can be integrated into any visualization tool as it is a generic image-based post-processing technique. Using highly diverse datasets, we show the usefulness of perception compensation across a wide range of typical visualizations.
In this paper, we propose a perceptually-guided visualization sharpening technique.We analyze the spectral behavior of an established comprehensive perceptual model to arrive at our approximated model based on an adapted weighting of the bandpass images from a Gaussian pyramid. The main benefit of this approximated model is its controllability and predictability for sharpening color-mapped visualizations. Our method can be integrated into any visualization tool as it adopts generic image-based post-processing, and it is intuitive and easy to use as viewing distance is the only parameter. Using highly diverse datasets, we show the usefulness of our method across a wide range of typical visualizations.
O. Abdullah, L. Dai, J. Tippetts, B. Zimmerman, A. Van Hoek, S. Joshi, E. Hsu.
High resolution and high field diffusion MRI in the visual system of primates (P3.086), In Neurology, Vol. 90, No. 15 Supplement, Wolters Kluwer Health, Inc, 2018.
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.
K. A. Aiello, S. P. Ponnapalli, O. Alter.
Mathematically universal and biologically consistent astrocytoma genotype encodes for transformation and predicts survival phenotype, In APL Bioengineering, Vol. 2, No. 3, AIP Publishing, pp. 031909. September, 2018.
DNA alterations have been observed in astrocytoma for decades. A copy-number genotype predictive of a survival phenotype was only discovered by using the generalized singular value decomposition (GSVD) formulated as a comparative spectral decomposition. Here, we use the GSVD to compare whole-genome sequencing (WGS) profiles of patient-matched astrocytoma and normal DNA. First, the GSVD uncovers a genome-wide pattern of copy-number alterations, which is bounded by patterns recently uncovered by the GSVDs of microarray-profiled patient-matched glioblastoma (GBM) and, separately, lower-grade astrocytoma and normal genomes. Like the microarray patterns, the WGS pattern is correlated with an approximately one-year median survival time. By filling in gaps in the microarray patterns, the WGS pattern reveals that this biologically consistent genotype encodes for transformation via the Notch together with the Ras and Shh pathways. Second, like the GSVDs of the microarray profiles, the GSVD of the WGS profiles separates the tumor-exclusive pattern from normal copy-number variations and experimental inconsistencies. These include the WGS technology-specific effects of guanine-cytosine content variations across the genomes that are correlated with experimental batches. Third, by identifying the biologically consistent phenotype among the WGS-profiled tumors, the GBM pattern proves to be a technology-independent predictor of survival and response to chemotherapy and radiation, statistically better than the patient's age and tumor's grade, the best other indicators, and MGMT promoter methylation and IDH1 mutation. We conclude that by using the complex structure of the data, comparative spectral decompositions underlie a mathematically universal description of the genotype-phenotype relations in cancer that other methods miss.
D. N. Anderson, B. Osting, J. Vorwerk, A. D Dorval, C. R Butson. Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes, In Journal of Neural Engineering, Vol. 15, No. 2, pp. 026005. 2018.
Objective. Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. Approach. Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). Main results. The optimization algorithm returns patient-specific contact configurations in near real-time—less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. Significance. This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.
Objective: During deep brain stimulation (DBS), it is well understood that extracellular cathodic stimulation can cause activation of passing axons. Activation can be predicted from the second derivative of the electric potential along an axon, which depends on axonal orientation with respect to the stimulation source. We hypothesize that fiber orientation influences activation thresholds and that fiber orientations can be selectively targeted with DBS waveforms. Approach: We used bioelectric field and multicompartment NEURON models to explore preferential activation based on fiber orientation during monopolar or bipolar stimulation. Preferential fiber orientation was extracted from the principal eigenvectors and eigenvalues of the Hessian matrix of the electric potential. We tested cathodic, anodic, and charge-balanced pulses to target neurons based on fiber orientation in general and clinical scenarios. Main Results: Axons passing the DBS lead have positive second derivatives around a cathode, whereas orthogonal axons have positive second derivatives around an anode, as indicated by the Hessian. Multicompartment NEURON models confirm that passing fibers are activated by cathodic stimulation, and orthogonal fibers are activated by anodic stimulation. Additionally, orthogonal axons have lower thresholds compared to passing axons. In a clinical scenario, fiber pathways associated with therapeutic benefit can be targeted with anodic stimulation at 50% lower stimulation amplitudes. Significance: Fiber orientations can be selectively targeted with simple changes to the stimulus waveform. Anodic stimulation preferentially activates orthogonal fibers, approaching or leaving the electrode, at lower thresholds for similar therapeutic benefit in DBS with decreased power consumption.
Finite Element Framework for Computational Fluid Dynamics in FEBio, In Journal of Biomechanical Engineering, Vol. 140, No. 2, ASME International, pp. 021001. Jan, 2018.
The mechanics of biological fluids is an important topic in biomechanics, often requiring the use of computational tools to analyze problems with realistic geometries and material properties. This study describes the formulation and implementation of a finite element framework for computational fluid dynamics (CFD) in FEBio, a free software designed to meet the computational needs of the biomechanics and biophysics communities. This formulation models nearly incompressible flow with a compressible isothermal formulation that uses a physically realistic value for the fluid bulk modulus. It employs fluid velocity and dilatation as essential variables: The virtual work integral enforces the balance of linear momentum and the kinematic constraint between fluid velocity and dilatation, while fluid density varies with dilatation as prescribed by the axiom of mass balance. Using this approach, equal-order interpolations may be used for both essential variables over each element, contrary to traditional mixed formulations that must explicitly satisfy the inf-sup condition. The formulation accommodates Newtonian and non-Newtonian viscous responses as well as inviscid fluids. The efficiency of numerical solutions is enhanced using Broyden's quasi-Newton method. The results of finite element simulations were verified using well-documented benchmark problems as well as comparisons with other free and commercial codes. These analyses demonstrated that the novel formulation introduced in FEBio could successfully reproduce the results of other codes. The analogy between this CFD formulation and standard finite element formulations for solid mechanics makes it suitable for future extension to fluid–structure interactions (FSIs).
A statistical framework for quantification and visualisation of positional uncertainty in deep brain stimulation electrodes, In Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, Taylor & Francis, pp. 1-12. 2018.
Deep brain stimulation (DBS) is an established therapy for treating patients with movement disorders such as Parkinson's disease. Patient-specific computational modelling and visualisation have been shown to play a key role in surgical and therapeutic decisions for DBS. The computational models use brain imaging, such as magnetic resonance (MR) and computed tomography (CT), to determine the DBS electrode positions within the patient's head. The finite resolution of brain imaging, however, introduces uncertainty in electrode positions. The DBS stimulation settings for optimal patient response are sensitive to the relative positioning of DBS electrodes to a specific neural substrate (white/grey matter). In our contribution, we study positional uncertainty in the DBS electrodes for imaging with finite resolution. In a three-step approach, we first derive a closed-form mathematical model characterising the geometry of the DBS electrodes. Second, we devise a statistical framework for quantifying the uncertainty in the positional attributes of the DBS electrodes, namely the direction of longitudinal axis and the contact-centre positions at subvoxel levels. The statistical framework leverages the analytical model derived in step one and a Bayesian probabilistic model for uncertainty quantification. Finally, the uncertainty in contact-centre positions is interactively visualised through volume rendering and isosurfacing techniques. We demonstrate the efficacy of our contribution through experiments on synthetic and real datasets. We show that the spatial variations in true electrode positions are significant for finite resolution imaging, and interactive visualisation can be instrumental in exploring probabilistic positional variations in the DBS lead.
D. Ayyagari, N. Ramesh, D. Yatsenko, T. Tasdizen, C. Atria. Image reconstruction using priors from deep learning, In Medical Imaging 2018: Image Processing, SPIE, March, 2018.
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.
Nonlinear stability and time step selection for the MPM method, In Computational Particle Mechanics, Jan, 2018.
The Material Point Method (MPM) has been developed from the Particle in Cell (PIC) method over the last 25 years and has proved its worth in solving many challenging problems involving large deformations. Nevertheless there are many open questions regarding the theoretical properties of MPM. For example in while Fourier methods, as applied to PIC may provide useful insight, the non-linear nature of MPM makes it necessary to use a full non-linear stability analysis to determine a stable time step for MPM. In order to begin to address this the stability analysis of Spigler and Vianello is adapted to MPM and used to derive a stable time step bound for a model problem. This bound is contrasted against traditional Speed of sound and CFL bounds and shown to be a realistic stability bound for a model problem.