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

Semantically Informed Multiview Surface Refinement

We present a method to jointly refine the geometry and semantic segmentation of 3D surface meshes. Our method alternates between updating the shape and the semantic labels. In the geometry refinement step, the mesh is deformed with variational energy minimization, such that it simultaneously maximizes photo-consistency and the compatibility of the semantic segmentations across a set of calibrated images. Label-specific shape priors account for interactions between the geometry and the semantic labels in 3D. In the semantic segmentation step, the labels on the mesh are updated with MRF inference, such that they are compatible with the semantic segmentations in the input images. Also, this step includes prior assumptions about the surface shape of different semantic classes. The priors induce a tight coupling, where semantic information influences the shape update and vice versa. Specifically, we introduce priors that favor (i) adaptive smoothing, depending on the class label; (ii) straightness of class boundaries; and (iii) semantic labels that are consistent with the surface orientation. The novel mesh-based reconstruction is evaluated in a series of experiments with real and synthetic data. We compare both to state-of-the-art, voxel-based semantic 3D reconstruction, and to purely geometric mesh refinement, and demonstrate that the proposed scheme yields improved 3D geometry as well as an improved semantic segmentation

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Second-order Shape Optimization for Geometric Inverse Problems in Vision

We develop a method for optimization in shape spaces, i.e., sets of surfaces modulo re-parametrization. Unlike previously proposed gradient flows, we achieve superlinear convergence rates through a subtle approximation of the shape Hessian, which is generally hard to compute and suffers from a series of degeneracies. Our analysis highlights the role of mean curvature motion in comparison with first-order schemes: instead of surface area, our approach penalizes deformation, either by its Dirichlet energy or total variation. Latter regularizer sparks the development of an alternating direction method of multipliers on triangular meshes. Therein, a conjugate-gradients solver enables us to bypass formation of the Gaussian normal equations appearing in the course of the overall optimization. We combine all of the aforementioned ideas in a versatile geometric variation-regularized Levenberg-Marquardt-type method applicable to a variety of shape functionals, depending on intrinsic properties of the surface such as normal field and curvature as well as its embedding into space. Promising experimental results are reported

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

Unified Heat Kernel Regression for Diffusion, Kernel Smoothing and Wavelets on Manifolds and Its Application to Mandible Growth Modeling in CT Images

We present a novel kernel regression framework for smoothing scalar surface data using the Laplace-Beltrami eigenfunctions. Starting with the heat kernel constructed from the eigenfunctions, we formulate a new bivariate kernel regression framework as a weighted eigenfunction expansion with the heat kernel as the weights. The new kernel regression is mathematically equivalent to isotropic heat diffusion, kernel smoothing and recently popular diffusion wavelets. Unlike many previous partial differential equation based approaches involving diffusion, our approach represents the solution of diffusion analytically, reducing numerical inaccuracy and slow convergence. The numerical implementation is validated on a unit sphere using spherical harmonics. As an illustration, we have applied the method in characterizing the localized growth pattern of mandible surfaces obtained in CT images from subjects between ages 0 and 20 years by regressing the length of displacement vectors with respect to the template surface.Comment: Accepted in Medical Image Analysi

The Spine of the Cosmic Web

We present the SpineWeb framework for the topological analysis of the Cosmic Web and the identification of its walls, filaments and cluster nodes. Based on the watershed segmentation of the cosmic density field, the SpineWeb method invokes the local adjacency properties of the boundaries between the watershed basins to trace the critical points in the density field and the separatrices defined by them. The separatrices are classified into walls and the spine, the network of filaments and nodes in the matter distribution. Testing the method with a heuristic Voronoi model yields outstanding results. Following the discussion of the test results, we apply the SpineWeb method to a set of cosmological N-body simulations. The latter illustrates the potential for studying the structure and dynamics of the Cosmic Web.Comment: Accepted for publication HIGH-RES version: http://skysrv.pha.jhu.edu/~miguel/SpineWeb