An Energy-Based Three Dimensional Segmentation Approach for the Quantitative Interpretation of Electron Tomograms
MINNESOTA UNIV MINNEAPOLIS INST FOR MATHEMATICS AND ITS APPLICATIONS
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Electron tomography allows determination of the three-dimensional structures of cells and tissues at resolutions significantly higher than is possible with optical microscopy. Electron tomograms contain, in principle, vast amounts of information on the locations and architectures of large numbers of subcellular assemblies and organelles. The development of reliable quantitative approaches for the analysis of features in tomograms is an important problem, and a challenging prospect due to the low signal-to-noise ratios that are inherent to biological electron microscopic images. This is in part a consequence of the tremendous complexity of biological specimens. We report on a new method for the automated segmentation of HIV particles and selected cellular compartments in electron tomograms recorded from fixed, plastic-embedded sections derived from HIV-infected human macrophages. Individual features in the tomogram are segmented using a novel robust algorithm that finds their boundaries as global minimal surfaces in a metric space defined by image features. The optimization is carried out in a transformed spherical domain with center the an interior point of the particle of interest, providing a proper setting for the fast and accurate minimization of the segmentation energy. This method provides tools for the semi-automated detection and statistical evaluation of HIV particles at different stages of assembly in the cells, and presents opportunities for correlation with biochemical markers of HIV infection. The segmentation algorithm developed here forms the basis of automated analysis of electron tomograms, and will be especially useful given the rapid increases in the rate of data acquisition. It could also enable studies of much larger data sets such as those which might be obtained from tomographic analysis of HIV-infected cells from studies of large populations.
- Medicine and Medical Research
- Numerical Mathematics
- Nuclear Physics and Elementary Particle Physics