The implementation of growth guidance factor diffusion via octree spatial structures for neuronal systems simulation

© Springer International Publishing AG 2018. The BioDynaMo project was created in CERN OpenLab V and aims to become a general platform for computer simulations for biological research. Important development stage was the code modernization by changing the architecture in a way to utilize multiple levels of parallelism offered by todays hardware. Individual neurons are implemented as spherical (for the soma) and cylindrical (for neurites) elements that have appropriate mechanical properties. The extracellular space is discretized, and allows for the diffusion of extracellular signaling molecules, as well as the physical interactions of the many developing neurons. This paper describes methods of the real-time growing brain dynamics simulation for BioDynaMo project, a specially the implementation of growth guidance factor diffusion via octree spatial structures

High Fidelity Bioelectric Modelling of the Implanted Cochlea

Cochlear implants are medical devices that can restore sound perception in individuals with sensorineural hearing loss (SHL). Since their inception, improvements in performance have largely been driven by advances in signal processing, but progress has plateaued for almost a decade. This suggests that there is a bottleneck at the electrode-tissue interface, which is responsible for enacting the biophysical changes that govern neuronal recruitment. Understanding this interface is difficult because the cochlea is small, intricate, and difficult to access. As such, researchers have turned to modelling techniques to provide new insights. The state-of-the-art involves calculating the electric field using a volume conduction model of the implanted cochlea and coupling it with a neural excitation model to predict the response. However, many models are unable to predict patient outcomes consistently. This thesis aims to improve the reliability of these models by creating high fidelity reconstructions of the inner ear and critically assessing the validity of the underlying and hitherto untested assumptions. Regarding boundary conditions, the evidence suggests that the unmodelled monopolar return path should be accounted for, perhaps by applying a voltage offset at a boundary surface. Regarding vasculature, the models show that large modiolar vessels like the vein of the scala tympani have a strong local effect near the stimulating electrode. Finally, it appears that the oft-cited quasi-static assumption is not valid due to the high permittivity of neural tissue. It is hoped that the study improves the trustworthiness of all bioelectric models of the cochlea, either by validating the claims of existing models, or by prompting improvements in future work. Developing our understanding of the underlying physics will pave the way for advancing future electrode array designs as well as patient-specific simulations, ultimately improving the quality of life for those with SHL

A Scalable Parallel Algorithm for the Simulation of Structural Plasticity in the Brain

The neural network in the brain is not hard-wired. Even in the mature brain, new connections between neurons are formed and existing ones are deleted, which is called structural plasticity. The dynamics of the connectome is key to understanding how learning, memory, and healing after lesions such as stroke work. However, with current experimental techniques even the creation of an exact static connectivity map, which is required for various brain simulations, is very difficult. One alternative is to use simulation based on network models to predict the evolution of synapses between neurons based on their specified activity targets. This is particularly useful as experimental measurements of the spiking frequency of neurons are more easily accessible and reliable than biological connectivity data. The Model of Structural Plasticity (MSP) by Butz and van Ooyen is an example of this approach. In traditional models, connectivity between neurons is fixed while plasticity merely arises from changes in the strength of existing synapses, typically modeled as weight factors. MSP, in contrast, models a synapse as a connection between an "axonal" plug and a "dendritic" socket. These synaptic elements grow and shrink independently on each neuron. When an axonal element of one neuron connects to the dendritic element of another neuron, a new synapse is formed. Conversely, when a synaptic element bound in a synapse retracts, the corresponding synapse is removed. The governing idea of the model is that plasticity in cortical networks is driven by the need of individual neurons to homeostatically maintain their average electrical activity. However, to predict which neurons connect to each other, the current MSP model computes probabilities for all pairs of neurons, resulting in a complexity O(n^2). To enable large-scale simulations with millions of neurons and beyond, this quadratic term is prohibitive. Inspired by hierarchical methods for solving n-body problems in particle physics, this dissertation presents a scalable approximation algorithm for simulating structural plasticity based on MSP. To scale MSP to millions of neurons, we adapt the Barnes-Hut algorithm as used in gravitational particle simulations to a scalable solution for the simulation of structural plasticity in the brain with a time complexity of O(n log^2 n) instead of O(n^2). Then, we show through experimental validation that the approximation underlying the algorithm does not adversely affect the quality of the results. For this purpose, we compare neural networks created by the original MSP with those created by our approximation of it using graph metrics. Finally, we prove that our scalable approximation algorithm can simulate the dynamics of the connectome with 10^9 neurons - four orders of magnitude more than the naive O(n^2) version, and two orders less than the human brain. We present an MPI-based scalable implementation of the scalable algorithm and our performance extrapolations predict that, given sufficient compute resources, even with today's technology a full-scale simulation of the human brain with 10^11 neurons is possible in principle. Until now, the scale of the largest structural plasticity simulations of MSP in terms of the number of neurons corresponded to that of a fruit fly. Our approximation algorithm goes a significant step further, reaching a scale similar to that of a galago primate. Additionally, large-scale brain connectivity maps can now be grown from scratch and their evolution after destructive events such as stroke can be simulated

Generation of realistic white matter substrates with controllable morphology for diffusion MRI simulations

Numerical phantoms have played a key role in the development of diffusion MRI (dMRI) techniques seeking to estimate features of the microscopic structure of tissue by providing a ground truth for simulation experiments against which we can validate and compare techniques. One common limitation of numerical phantoms which represent white matter (WM) is that they oversimplify the true complex morphology of the tissue which has been revealed through ex vivo studies. It is important to try to generate WM numerical phantoms that capture this realistic complexity in order to understand how it impacts the dMRI signal. This thesis presents work towards improving the realism of WM numerical phantoms by generating fibres mimicking natural fibre genesis. A novel phantom generator is presented which was developed over two works, resulting in Contextual Fibre Growth (ConFiG). ConFiG grows fibres one-by-one, following simple rules motivated by real axonal guidance mechanisms. These simple rules enable ConFiG to generate phantoms with tuneable microstructural features by growing fibres while attempting to meet morphological targets such as user-specified density and orientation distribution. We compare ConFiG to the state-of-the-art approach based on packing fibres together by generating phantoms in a range of fibre configurations including crossing fibre bundles and orientation dispersion. Results demonstrate that ConFiG produces phantoms with up to 20% higher densities than the state-of-the-art, particularly in complex configurations with crossing fibres. We additionally show that the microstructural morphology of ConFiG phantoms is comparable to real tissue, producing diameter and orientation distributions close to electron microscopy estimates from real tissue as well as capturing complex fibre cross sections. ConFiG is applied to investigate the intra-axonal diffusivity and probe assumptions in a family of dMRI modelling techniques based on spherical deconvolution (SD), demonstrating that the microscopic variations in fibres’ shapes affects the diffusion within axons. This leads to variations in the per-fibre signal contrary to the assumptions inherent in SD which may have a knock-on effect in popular techniques such as tractography

Proceedings, MSVSCC 2014

Proceedings of the 8th Annual Modeling, Simulation & Visualization Student Capstone Conference held on April 17, 2014 at VMASC in Suffolk, Virginia

Deep Model for Improved Operator Function State Assessment

A deep learning framework is presented for engagement assessment using EEG signals. Deep learning is a recently developed machine learning technique and has been applied to many applications. In this paper, we proposed a deep learning strategy for operator function state (OFS) assessment. Fifteen pilots participated in a flight simulation from Seattle to Chicago. During the four-hour simulation, EEG signals were recorded for each pilot. We labeled 20- minute data as engaged and disengaged to fine-tune the deep network and utilized the remaining vast amount of unlabeled data to initialize the network. The trained deep network was then used to assess if a pilot was engaged during the four-hour simulation

Geodesic Active Fields:A Geometric Framework for Image Registration

Image registration is the concept of mapping homologous points in a pair of images. In other words, one is looking for an underlying deformation field that matches one image to a target image. The spectrum of applications of image registration is extremely large: It ranges from bio-medical imaging and computer vision, to remote sensing or geographic information systems, and even involves consumer electronics. Mathematically, image registration is an inverse problem that is ill-posed, which means that the exact solution might not exist or not be unique. In order to render the problem tractable, it is usual to write the problem as an energy minimization, and to introduce additional regularity constraints on the unknown data. In the case of image registration, one often minimizes an image mismatch energy, and adds an additive penalty on the deformation field regularity as smoothness prior. Here, we focus on the registration of the human cerebral cortex. Precise cortical registration is required, for example, in statistical group studies in functional MR imaging, or in the analysis of brain connectivity. In particular, we work with spherical inflations of the extracted hemispherical surface and associated features, such as cortical mean curvature. Spatial mapping between cortical surfaces can then be achieved by registering the respective spherical feature maps. Despite the simplified spherical geometry, inter-subject registration remains a challenging task, mainly due to the complexity and inter-subject variability of the involved brain structures. In this thesis, we therefore present a registration scheme, which takes the peculiarities of the spherical feature maps into particular consideration. First, we realize that we need an appropriate hierarchical representation, so as to coarsely align based on the important structures with greater inter-subject stability, before taking smaller and more variable details into account. Based on arguments from brain morphogenesis, we propose an anisotropic scale-space of mean-curvature maps, built around the Beltrami framework. Second, inspired by concepts from vision-related elements of psycho-physical Gestalt theory, we hypothesize that anisotropic Beltrami regularization better suits the requirements of image registration regularization, compared to traditional Gaussian filtering. Different objects in an image should be allowed to move separately, and regularization should be limited to within the individual Gestalts. We render the regularization feature-preserving by limiting diffusion across edges in the deformation field, which is in clear contrast to the indifferent linear smoothing. We do so by embedding the deformation field as a manifold in higher-dimensional space, and minimize the associated Beltrami energy which represents the hyperarea of this embedded manifold as measure of deformation field regularity. Further, instead of simply adding this regularity penalty to the image mismatch in lieu of the standard penalty, we propose to incorporate the local image mismatch as weighting function into the Beltrami energy. The image registration problem is thus reformulated as a weighted minimal surface problem. This approach has several appealing aspects, including (1) invariance to re-parametrization and ability to work with images defined on non-flat, Riemannian domains (e.g., curved surfaces, scalespaces), and (2) intrinsic modulation of the local regularization strength as a function of the local image mismatch and/or noise level. On a side note, we show that the proposed scheme can easily keep up with recent trends in image registration towards using diffeomorphic and inverse consistent deformation models. The proposed registration scheme, called Geodesic Active Fields (GAF), is non-linear and non-convex. Therefore we propose an efficient optimization scheme, based on splitting. Data-mismatch and deformation field regularity are optimized over two different deformation fields, which are constrained to be equal. The constraint is addressed using an augmented Lagrangian scheme, and the resulting optimization problem is solved efficiently using alternate minimization of simpler sub-problems. In particular, we show that the proposed method can easily compete with state-of-the-art registration methods, such as Demons. Finally, we provide an implementation of the fast GAF method on the sphere, so as to register the triangulated cortical feature maps. We build an automatic parcellation algorithm for the human cerebral cortex, which combines the delineations available on a set of atlas brains in a Bayesian approach, so as to automatically delineate the corresponding regions on a subject brain given its feature map. In a leave-one-out cross-validation study on 39 brain surfaces with 35 manually delineated gyral regions, we show that the pairwise subject-atlas registration with the proposed spherical registration scheme significantly improves the individual alignment of cortical labels between subject and atlas brains, and, consequently, that the estimated automatic parcellations after label fusion are of better quality