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

Correcting curvature-density effects in the Hamilton-Jacobi skeleton

The Hainilton-Jacobi approach has proven to be a powerful and elegant method for extracting the skeleton of two-dimensional (2-D) shapes. The approach is based on the observation that the normalized flux associated with the inward evolution of the object boundary at nonskeletal points tends to zero as the size of the integration area tends to zero, while the flux is negative at the locations of skeletal points. Nonetheless, the error in calculating the flux on the image lattice is both limited by the pixel resolution and also proportional to the curvature of the boundary evolution front and, hence, unbounded near endpoints. This makes the exact location of endpoints difficult and renders the performance of the skeleton extraction algorithm dependent on a threshold parameter. This problem can be overcome by using interpolation techniques to calculate the flux with subpixel precision. However, here, we develop a method for 2-D skeleton extraction that circumvents the problem by eliminating the curvature contribution to the error. This is done by taking into account variations of density due to boundary curvature. This yields a skeletonization algorithm that gives both better localization and less susceptibility to boundary noise and parameter choice than the Hamilton-Jacobi method

Multiscale Geometric Modeling of Macromolecules I: Cartesian Representation

This paper focuses on the geometric modeling and computational algorithm development of biomolecular structures from two data sources: Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB) in the Eulerian (or Cartesian) representation. Molecular surface (MS) contains non-smooth geometric singularities, such as cusps, tips and self-intersecting facets, which often lead to computational instabilities in molecular simulations, and violate the physical principle of surface free energy minimization. Variational multiscale surface definitions are proposed based on geometric flows and solvation analysis of biomolecular systems. Our approach leads to geometric and potential driven Laplace–Beltrami flows for biomolecular surface evolution and formation. The resulting surfaces are free of geometric singularities and minimize the total free energy of the biomolecular system. High order partial differential equation (PDE)-based nonlinear filters are employed for EMDB data processing. We show the efficacy of this approach in feature-preserving noise reduction. After the construction of protein multiresolution surfaces, we explore the analysis and characterization of surface morphology by using a variety of curvature definitions. Apart from the classical Gaussian curvature and mean curvature, maximum curvature, minimum curvature, shape index, and curvedness are also applied to macromolecular surface analysis for the first time. Our curvature analysis is uniquely coupled to the analysis of electrostatic surface potential, which is a by-product of our variational multiscale solvation models. As an expository investigation, we particularly emphasize the numerical algorithms and computational protocols for practical applications of the above multiscale geometric models. Such information may otherwise be scattered over the vast literature on this topic. Based on the curvature and electrostatic analysis from our multiresolution surfaces, we introduce a new concept, the polarized curvature, for the prediction of protein binding sites

Diffeomorphic Metric Mapping of High Angular Resolution Diffusion Imaging based on Riemannian Structure of Orientation Distribution Functions

In this paper, we propose a novel large deformation diffeomorphic registration algorithm to align high angular resolution diffusion images (HARDI) characterized by orientation distribution functions (ODFs). Our proposed algorithm seeks an optimal diffeomorphism of large deformation between two ODF fields in a spatial volume domain and at the same time, locally reorients an ODF in a manner such that it remains consistent with the surrounding anatomical structure. To this end, we first review the Riemannian manifold of ODFs. We then define the reorientation of an ODF when an affine transformation is applied and subsequently, define the diffeomorphic group action to be applied on the ODF based on this reorientation. We incorporate the Riemannian metric of ODFs for quantifying the similarity of two HARDI images into a variational problem defined under the large deformation diffeomorphic metric mapping (LDDMM) framework. We finally derive the gradient of the cost function in both Riemannian spaces of diffeomorphisms and the ODFs, and present its numerical implementation. Both synthetic and real brain HARDI data are used to illustrate the performance of our registration algorithm

A Spatiotemporal Volumetric Interpolation Network for 4D Dynamic Medical Image

Dynamic medical imaging is usually limited in application due to the large radiation doses and longer image scanning and reconstruction times. Existing methods attempt to reduce the dynamic sequence by interpolating the volumes between the acquired image volumes. However, these methods are limited to either 2D images and/or are unable to support large variations in the motion between the image volume sequences. In this paper, we present a spatiotemporal volumetric interpolation network (SVIN) designed for 4D dynamic medical images. SVIN introduces dual networks: first is the spatiotemporal motion network that leverages the 3D convolutional neural network (CNN) for unsupervised parametric volumetric registration to derive spatiotemporal motion field from two-image volumes; the second is the sequential volumetric interpolation network, which uses the derived motion field to interpolate image volumes, together with a new regression-based module to characterize the periodic motion cycles in functional organ structures. We also introduce an adaptive multi-scale architecture to capture the volumetric large anatomy motions. Experimental results demonstrated that our SVIN outperformed state-of-the-art temporal medical interpolation methods and natural video interpolation methods that have been extended to support volumetric images. Our ablation study further exemplified that our motion network was able to better represent the large functional motion compared with the state-of-the-art unsupervised medical registration methods.Comment: 10 pages, 8 figures, Conference on Computer Vision and Pattern Recognition (CVPR) 202

3D geomodelling combining implicit surfaces and Voronoi-based remeshing: A case study in the Lorraine Coal Basin (France)

International audienceIn this paper we demonstrate how recent geomodelling techniques can be combined and used to build a 3D geological model on a real case study: the former coal mine of Merlebach (France), that is targeted to be exploited for low-temperature geothermal energy production. From geological maps, cross-sections, borehole and mine exploitation data, we build a 3D model in which are identified the rocks and infrastructures having significantly different permeabilities. First, a structural model of the main geological interfaces in our area of interest (2 horizons and 13 faults) is built with classical geomodelling techniques. Then, we propose to model by surfaces the 71 irregularly stacked, very close and very thin, subvertical coal beds. To ease their construction, we use an implicit method which represents 3D surfaces as isovalues of a scalar field defined in a 3D tetrahedral grid of the area. The corresponding triangulated surfaces are remeshed with a recently proposed method based on Voronoi diagrams so that the exploited parts of the coal beds, now filled by sand, can be computed. The 3D surface-based geological model, in which infrastructures can be inserted as piecewise lines, can be volumetrically meshed. It is available for download as supplemental material, as well as a volumetric grid