Biomedical Imaging Group Software Overview

Over the last three decades, the BIG has written and validated a large collection of software tools (hundreds of programs) for image acquisition, processing, analysis and visualization, image restoration, computer vision, and the modeling and simulation of biological systems. The bulk of this software is written in C, as well as in Fortran, C++, Perl, Java and Matlab. These programs range from the simple (e.g., add/subtract/multiply/divide images; perform global thresholding, etc.) to the complex (e.g., deformable models to identify the plasma membrane of a cell). The following is a description of many of the programs, roughly sorted by category. Some of the larger or more important programs are listed at the end with a short description and a link to a separate web page which provides further information.
Note: a much more complete list of BIG software is described here
This software was written, primarily, by BIG members Kevin Fogarty , Lawrence Lifshitz (this includes an overview of my research areas and a full bibliography) , and Karl Bellve .

Generating Random Data/Simulations:


Finding events, Tracking:


Shrinkwrap - a Deformable Surfaces program

Deforming Surface We have developed and implemented a deformable surface model [Lifshitz, L. M., Fogarty, K. E., Gauch, J. M. & Moore, E. D. W. "Computer vision and graphics in fluorescence microscopy". Visualization in Biomedical Computing, SPIE vol. 1808, 521-534 (1992)], called "shrinkwrap" which has been used numerous times over the years to locate the plasma membrane of fluorescently labeled cells. The model is composed of vertices spaced along a model surface, which is initially placed within a 3D image, near its correct location. Each vertex is then allowed move in response to image intensity gradients, attempting to move to locations in the image with a higher intensity while imposing a cost based upon how much curvature its position would impose onto the surface. Our implementation calculates curvature measures (i.e., first and second derivatives of the surface) and intensity measures locally and quickly. This results in a fast algorithm, which is also easy to modify to handle additional local constraints.

CellSim - simulating chemical reactions and diffusion in 3D cells.

Cellsim [Kargacin, G., and F.S. Fay. 1991. "Ca2+ movement in smooth muscle cells studied with one- and two-dimensional diffusion model" Biophys. J. 60:1088-1100. and Zou, H.L., M. Lifshitz, R.A. Tuft, K.E. Fogarty, and J.J. Singer. 1999. "Imaging Ca2+ entering the cytoplasm through a single opening of a plasma membrane cation channel". J. Gen. Physiol. 114:575-588. ] is a program for 3-D reaction and diffusion simulation. Cellsim uses a Forward Time Centered Space fully explicit differencing scheme to solve the associated PDEs. Cellsim can run in parallel using MPI. Cellsim models multiple species of diffusible molecules and their reactions (e.g. ions and their binding targets). The simulation is saved as a series of images at specified time intervals. Images explicitly describing flow (since there can be large flow yet no net change in concentration) can also be saved.

DAVE - Interactive quantitative visualization of multidimensional image data

Moving Cell, z dim = time The Data Visualization and Analysis Environment [Lifshitz, L. M., Collins, J. A., Moore, E. D. W. & Gauch, J., "Computer vision and graphics in fluorescence microscopy". IEEE Workshop on Biomedical Image Analysis, Seattle, 1994. pp. 166-175. doi:10.1109/BIA.1994.315854] is a real-time interactive software system for displaying and analyzing multi-wavelength, 3-D, time-series images. DAVE simultaneously displays up to three image stacks, in red, green and blue. The images can be displayed as 2-D slices or full 3-D volumes, using several different methods for volume rendering. Surfaces (polygonal) or outlines (polyline) can be simultaneously displayed with volumes. Time series can be interactively reviewed in real-time, with selected time points held on screen for visual reference. Pixels or voxels of co-localization among the three images sets can be visually highlighted, segmented, and quantified50 . DAVE calculates percentage of overlap of regions of images, and the probability that such overlap could have occurred randomly. DAVE can render voxels as an individual cubes when the location or value of an individual voxel is desired. An "intelligent" 3-D cursor automatically snaps to the brightest nearby voxel when clicked. DAVE can remotely synchronize with another instance of DAVE, thus researchers in different locations see and interact with the same exact views.

EPR - Image Restoration and super-resolution.

Over 20 years ago the BIG pioneered the development of image deconvolution for light microscopy and the resulting EPR algorithm 25 remains one of the best. EPR uses the light microscope's point spread function (PSF) in an iterative process to move out-of-focus light back to its originating position. Unlike many image restoration algorithms it is guaranteed to converge, and when given a finely-sampled point spread function it has been shown to increase lateral image resolution beyond the diffraction limit to less than 100 nm/pixel25. When combined with structured light microscopy (i.e. Structured Light Epifluorescence EPR or SLEEPR) it can achieve resolutions better than 50 nm laterally and 250 nm axially. EPR is computationally demanding. Original versions of this software were written by Kevin Fogarty. More recently Dr. Bellvé has produced both cluster-enabled and GPU versions of EPR, the latter of which can now restore images in seconds on a single workstation, make EPR for the first time amenable for High-Througput, high-speed and intelligent acquisition modalitis.

SignalMass - quantifying intracellular calcium microdomains.

SignalMass [ZhuGe, R., Fogarty, K., Tuft, R., Lifshitz, L., Sayar, K., and Walsh, J. "Dynamics of signaling between Ca(2+) sparks and Ca(2+)- activated K(+) channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca(2+) current". J Gen Physiol 116, 845-864 (2000).] is program for the analysis of fast, time-lapse images of live cells loaded with a fluorescent calcium indicator for spatially and temporal local (microdomain) events (flashes of light) representing the release of calcium from internal stores through events called calcium "sparks" and "puffs".
During a Ca2+ "spark", free Ca2+ and Ca2+ bound to fluo-3 quickly diffuse away from the spark release site as Ca2+ continues to be discharged. To quantify the total fluorescence (and, ultimately the total Ca2+ discharged) arising from the binding of fluo-3 to the discharged Ca2+(i.e., the Ca2+ signal mass), the increase in fluo3/fluo4 fluorescence ) must be collected from a sufficiently large volume (and in 3D) to provide a measure of the total quantity of Ca2+ released. This software was written by Kevin Fogarty.