The Three-D Informatics Group in the NLM Office of High Performance Computing and Communications (OHPCC) 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 (APDB) 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 Institute's 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 by Harvard's National Alliance for Medical Image Computing (NA-MIC) one of the NIH Roadmap National Centers for Biomedical Computing (NCBCs) funded through NIBIB. Since FY2009, the team, led by the programming efforts of Mr. Lowekamp, has provided software tools to NCI's Laboratory of Cell Biology to promote high throughput microscopy and improve their understanding of cellular biology, particularly in the communication of HIV AIDS among dendritic 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. Lowekamp's cell membrane models generated through his software and illuminated by Mr. Bliss was presented on the cover of the November-December 2009 IAVI Report (the publication on AIDS Vaccine Research), volume 13, number 6, with the subtitle Visualizing HIV. Other publications include a study of the transfer of HIV to T cells described in the Proceedings of the National Academy of Sciences. NCI acquired a new microscope in FY2011 that produces images with improved resolution, greater contrast, and greater relative signal to noise properties. Software developed for the new data is beginning to enable a range of new discoveries. In addition to software development, over the past year staff from the OHPCC and APDB created visualizations and 3D models of protein spikes from the surface of HIV virions as part of the scientific review of this research program conducted by NCI. This project remains in its early stages, but the collaboration continues to yield important results and multiple publications in journals and conferences demonstrating the value of these technologies.
