VolRoverN: Enhancing Surface and Volumetric Reconstruction for Realistic Dynamical Simulation of Cellular and Subcellular Function

Establishing meaningful relationships between cellular structure and function requires accurate morphological reconstructions. In particular, there is an unmet need for high quality surface reconstructions to model subcellular and synaptic interactions among neurons and glia at nanometer resolution. We address this need with VolRoverN, a software package that produces accurate, efficient, and automated 3D surface reconstructions from stacked 2D contour tracings. While many techniques and tools have been developed in the past for 3D visualization of cellular structure, the reconstructions from VolRoverN meet specific quality criteria that are important for dynamical simulations. These criteria include manifoldness, water-tightness, lack of self- and object-object-intersections, and geometric accuracy. These enhanced surface reconstructions are readily extensible to any cell type and are used here on spiny dendrites with complex morphology and axons from mature rat hippocampal area CA1. Both spatially realistic surface reconstructions and reduced skeletonizations are produced and formatted by VolRoverN for easy input into analysis software packages for neurophysiological simulations at multiple spatial and temporal scales ranging from ion electro-diffusion to electrical cable models

3D mesh processing using GAMer 2 to enable reaction-diffusion simulations in realistic cellular geometries

Recent advances in electron microscopy have enabled the imaging of single cells in 3D at nanometer length scale resolutions. An uncharted frontier for in silico biology is the ability to simulate cellular processes using these observed geometries. Enabling such simulations requires watertight meshing of electron micrograph images into 3D volume meshes, which can then form the basis of computer simulations of such processes using numerical techniques such as the Finite Element Method. In this paper, we describe the use of our recently rewritten mesh processing software, GAMer 2, to bridge the gap between poorly conditioned meshes generated from segmented micrographs and boundary marked tetrahedral meshes which are compatible with simulation. We demonstrate the application of a workflow using GAMer 2 to a series of electron micrographs of neuronal dendrite morphology explored at three different length scales and show that the resulting meshes are suitable for finite element simulations. This work is an important step towards making physical simulations of biological processes in realistic geometries routine. Innovations in algorithms to reconstruct and simulate cellular length scale phenomena based on emerging structural data will enable realistic physical models and advance discovery at the interface of geometry and cellular processes. We posit that a new frontier at the intersection of computational technologies and single cell biology is now open.Comment: 39 pages, 14 figures. High resolution figures and supplemental movies available upon reques

Doctor of Philosophy

dissertationOne of the fundamental building blocks of many computational sciences is the construction and use of a discretized, geometric representation of a problem domain, often referred to as a mesh. Such a discretization enables an otherwise complex domain to be represented simply, and computation to be performed over that domain with a finite number of basis elements. As mesh generation techniques have become more sophisticated over the years, focus has largely shifted to quality mesh generation techniques that guarantee or empirically generate numerically well-behaved elements. In this dissertation, the two complementary meshing subproblems of vertex placement and element creation are analyzed, both separately and together. First, a dynamic particle system achieves adaptivity over domains by inferring feature size through a new information passing algorithm. Second, a new tetrahedral algorithm is constructed that carefully combines lattice-based stenciling and mesh warping to produce guaranteed quality meshes on multimaterial volumetric domains. Finally, the ideas of lattice cleaving and dynamic particle systems are merged into a unified framework for producing guaranteed quality, unstructured and adaptive meshing of multimaterial volumetric domains

Flexible isosurfaces: Simplifying and displaying scalar topology using the contour tree

The contour tree is an abstraction of a scalar field that encodes the nesting relationships of isosurfaces. We show how to use the contour tree to represent individual contours of a scalar field, how to simplify both the contour tree and the topology of the scalar field, how to compute and store geometric properties for all possible contours in the contour tree, and how to use the simplified contour tree as an interface for exploratory visualization

Multi-Material Mesh Representation of Anatomical Structures for Deep Brain Stimulation Planning

The Dual Contouring algorithm (DC) is a grid-based process used to generate surface meshes from volumetric data. However, DC is unable to guarantee 2-manifold and watertight meshes due to the fact that it produces only one vertex for each grid cube. We present a modified Dual Contouring algorithm that is capable of overcoming this limitation. The proposed method decomposes an ambiguous grid cube into a set of tetrahedral cells and uses novel polygon generation rules that produce 2-manifold and watertight surface meshes with good-quality triangles. These meshes, being watertight and 2-manifold, are geometrically correct, and therefore can be used to initialize tetrahedral meshes. The 2-manifold DC method has been extended into the multi-material domain. Due to its multi-material nature, multi-material surface meshes will contain non-manifold elements along material interfaces or shared boundaries. The proposed multi-material DC algorithm can (1) generate multi-material surface meshes where each material sub-mesh is a 2-manifold and watertight mesh, (2) preserve the non-manifold elements along the material interfaces, and (3) ensure that the material interface or shared boundary between materials is consistent. The proposed method is used to generate multi-material surface meshes of deep brain anatomical structures from a digital atlas of the basal ganglia and thalamus. Although deep brain anatomical structures can be labeled as functionally separate, they are in fact continuous tracts of soft tissue in close proximity to each other. The multi-material meshes generated by the proposed DC algorithm can accurately represent the closely-packed deep brain structures as a single mesh consisting of multiple material sub-meshes. Each sub-mesh represents a distinct functional structure of the brain. Printed and/or digital atlases are important tools for medical research and surgical intervention. While these atlases can provide guidance in identifying anatomical structures, they do not take into account the wide variations in the shape and size of anatomical structures that occur from patient to patient. Accurate, patient-specific representations are especially important for surgical interventions like deep brain stimulation, where even small inaccuracies can result in dangerous complications. The last part of this research effort extends the discrete deformable 2-simplex mesh into the multi-material domain where geometry-based internal forces and image-based external forces are used in the deformation process. This multi-material deformable framework is used to segment anatomical structures of the deep brain region from Magnetic Resonance (MR) data

Volumetric data analysis using Morse-Smale complexes

The 3D Morse-Smale complex is a fundamental topological construct that partitions the domain of a real-valued function into regions having uniform gradient flow behavior. In this paper, we consider the construction and selective presentation of cells of the Morse-Smale complex and their use in the analysis and visualization of scientific datasets. We take advantage of the fact that cells of different dimension often characterize different types of features present in the data. For example, critical points pinpoint changes in topology by showing where components of the level sets are created, destroyed or modified in genus. Edges of the Morse-Smale complex extract filament-like features that are not explicitly modeled in the original data. Interactive selection and rendering of portions of the Morse-Smale complex introduces fundamental data management challenges due to the unstructured nature of the complex even for structured inputs. We describe a data structure that stores the Morse-Smale complex and allows efficient selective traversal of regions of interest. Finally, we illustrate the practical use of this approach by applying it to cryo-electron microscopy data of protein molecules

Segmentation and Deformable Modelling Techniques for a Virtual Reality Surgical Simulator in Hepatic Oncology

Liver surgical resection is one of the most frequently used curative therapies. However, resectability is problematic. There is a need for a computer-assisted surgical planning and simulation system which can accurately and efficiently simulate the liver, vessels and tumours in actual patients. The present project describes the development of these core segmentation and deformable modelling techniques. For precise detection of irregularly shaped areas with indistinct boundaries, the segmentation incorporated active contours - gradient vector flow (GVF) snakes and level sets. To improve efficiency, a chessboard distance transform was used to replace part of the GVF effort. To automatically initialize the liver volume detection process, a rotating template was introduced to locate the starting slice. For shape maintenance during the segmentation process, a simplified object shape learning step was introduced to avoid occasional significant errors. Skeletonization with fuzzy connectedness was used for vessel segmentation. To achieve real-time interactivity, the deformation regime of this system was based on a single-organ mass-spring system (MSS), which introduced an on-the-fly local mesh refinement to raise the deformation accuracy and the mesh control quality. This method was now extended to a multiple soft-tissue constraint system, by supplementing it with an adaptive constraint mesh generation. A mesh quality measure was tailored based on a wide comparison of classic measures. Adjustable feature and parameter settings were thus provided, to make tissues of interest distinct from adjacent structures, keeping the mesh suitable for on-line topological transformation and deformation. More than 20 actual patient CT and 2 magnetic resonance imaging (MRI) liver datasets were tested to evaluate the performance of the segmentation method. Instrument manipulations of probing, grasping, and simple cutting were successfully simulated on deformable constraint liver tissue models. This project was implemented in conjunction with the Division of Surgery, Hammersmith Hospital, London; the preliminary reality effect was judged satisfactory by the consultant hepatic surgeon

Multi-Surface Simplex Spine Segmentation for Spine Surgery Simulation and Planning

This research proposes to develop a knowledge-based multi-surface simplex deformable model for segmentation of healthy as well as pathological lumbar spine data. It aims to provide a more accurate and robust segmentation scheme for identification of intervertebral disc pathologies to assist with spine surgery planning. A robust technique that combines multi-surface and shape statistics-aware variants of the deformable simplex model is presented. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user-assistance is allowed to disable the prior shape influence during deformation. Results have been validated against user-assisted expert segmentation