The Three-D Informatics Group in the NLM Office of High Performance Computing and Communications is developing software for the registration, segmentation, analysis and visualization of 3D data from confocal microscopy, transmission electron tomography, and high resolution dual-beam scanning electron microscopy. These technologies are exploring cell biology at nanometer scales. The Audio Visual Program Development Branch craft individual models, visualizations, and presentations of the processed data from these modalities of microscopy for publication and interactive viewing among our colleagues in the biological sciences. We are conducting this research in partnership with the National Cancer Institutes Laboratory for Cell Biology. These technologies resemble the very successful Visible Human Project (VHP), where cryosectioning, a destructive imaging technique, was used to capture a representation of human anatomy at unprecedented levels of quality and fidelity. Effectively, a human subject was sliced at 1/3 mm intervals and the exposed sections photographed digitally to yield a human anatomical study with pixel resolutions as fine as 350 microns. In a similar approach, dual-beam scanning electron microscopy starts with a fixed cellular sample and ablates the cell using a focused ion beam, slicing the sample at intervals as fine as 15 nanometers. The exposed sections are imaged using a scanning electron microscope. The comparable approaches of these imaging techniques allow the Three-D Informatics Group to apply tools similar to those used on VHP data for registration, segmentation, and image analysis. The very successful VHP Insight Toolkit (ITK) open source software initiative sponsored by NLM and originally funded with other ICs at NIH (NIDCR, NEI, NIMH, NINDS, NCI), the National Science Foundation, and DoD TATRC, are used extensively in this project. We also employ public tools such as 3D Slicer, a software system that uses ITK and is produced Harvards National Alliance for Medical Image Computing (NA-MIC) one of the NIH Roadmap National Centers for Biomedical Computing (NCBCs) funded through NIBIB. During FY2009, the team, led by the programming efforts of Mr. Lowekamp, has provided software tools to NCIs Laboratory of Cell Biology to promote high throughput microscopy and improve their understanding of cellular biology, particularly in the communication of HIV AIDS among dendrite cells, macrophages, and T-Cells. Illuminations from Mr. Bliss of the Audiovisual Program Development Branch have aided in communicating these results and their importance to the community. These results have been published in journals including the Journal of Structural Biology. One of the images that features one of Mr. Lowekamps cell membrane models generated through his software and illuminated by Mr. Bliss was presented on the cover of the November-December 2009 IAVIReport (the publication on AIDS Vaccine Research), volume 13, number 6, with the subtitle Visualizing HIV. The current effort focuses on new processing software for the incoming microscope being acquired by NCI. The new instrument promises far greater resolution, better signal to noise properties, and excellent contrast. Our ability to build effective software tools to extract information will be greatly enhanced by these new developments. This project still in its early stages, but the collaboration has already yielded important results and multiple publications in journals and conferences demonstrating the value of these technologies.

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