120,826 research outputs found
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
Two-photon microscopy : sequential imaging studies in vivo
Microscopists have always desired to look inside various organ tissues to study structure, function and dysfunction of their cellular constituents. In the past, this has frequently required tissue extraction and histological preparation to gain access. Traditional optical microscopy techniques, which use linear (one-photon) absorption processes for contrast generation, are limited to use near the tissue surface (< 80 µm) because at greater depths strong and multiple light scattering blurs the images. Scattering particularly strongly affects signal strength in confocal microscopy, which achieves three-dimensional resolution and optical sectioning with a detection pinhole that rejects all light that appears not to originate from the focus. New optical microscopy techniques have been developed that use nonlinear light-matter interactions to generate signal contrast only within a thin raster-scanned plane. Since its first demonstration over a decade ago, two-photon microscopy has been applied to a variety of imaging tasks and has now become the technique of choice for fluorescence microscopy in thick tissue preparations and in live animals. The gain in resolution over conventional in vivo imaging techniques has been several orders of magnitude. Neuroscientists have used it to measure calcium dynamics deep in brain slices and in live animals, blood flow measurement, neuronal plasticity and to monitor neurodegenerative disease models in brain slices and in live rodents. These types of applications define the most important niche for two-photon microscopy - high-resolution imaging of physiology, morphology and cell-cell interactions in intact tissue. Clearly the biggest advantage of two-photon microscopy is in longitudinal monitoring of rodent models of disease or plasticity over days to weeks. The aim of this article is to discuss some methodological principles, and show some applications of this technique obtained from our laboratory in the area of acute experimental stroke research.peer-reviewe
Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)
A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation
PPF - A Parallel Particle Filtering Library
We present the parallel particle filtering (PPF) software library, which
enables hybrid shared-memory/distributed-memory parallelization of particle
filtering (PF) algorithms combining the Message Passing Interface (MPI) with
multithreading for multi-level parallelism. The library is implemented in Java
and relies on OpenMPI's Java bindings for inter-process communication. It
includes dynamic load balancing, multi-thread balancing, and several
algorithmic improvements for PF, such as input-space domain decomposition. The
PPF library hides the difficulties of efficient parallel programming of PF
algorithms and provides application developers with the necessary tools for
parallel implementation of PF methods. We demonstrate the capabilities of the
PPF library using two distributed PF algorithms in two scenarios with different
numbers of particles. The PPF library runs a 38 million particle problem,
corresponding to more than 1.86 GB of particle data, on 192 cores with 67%
parallel efficiency. To the best of our knowledge, the PPF library is the first
open-source software that offers a parallel framework for PF applications.Comment: 8 pages, 8 figures; will appear in the proceedings of the IET Data
Fusion & Target Tracking Conference 201
Membrane shape as a reporter for applied forces
Recent advances have enabled 3-dimensional reconstructions of biological structures in vivo, ranging in size and complexity from single proteins to multicellular structures. In particular, tomography and confocal microscopy have been exploited to capture detailed 3-dimensional conformations of membranes in cellular processes ranging from viral budding and organelle maintenance to phagocytosis. Despite the wealth of membrane structures available, there is as yet no generic, quantitative method for their interpretation. We propose that by modeling these observed biomembrane shapes as fluid lipid bilayers in mechanical equilibrium, the externally applied forces as well as the pressure, tension, and spontaneous curvature can be computed directly from the shape alone. To illustrate the potential power of this technique, we apply an axial force with optical tweezers to vesicles and explicitly demonstrate that the applied force is equal to the force computed from the membrane conformation
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