Accurate 3D reconstruction of biological tissue is technologically challenging. The proposed project will fund acquisition of an instrument to accommodate high-resolution reconstruction of large tissue samples and would support histology of very hard bone samples. The system is based on a Leica Cryopolycut, a large horizontal cryostat. Modification of the basic system will permit imaging the tissue block face at unprecedented resolution. Using already available techniques, these block face images would guide accurate registration of consecutive tissue sections. The proposed instrument will be housed in the Computer Vision Center for Vertebrate Brain Mapping (CVCVBM), a NIH Biomedical Technology Resource. Three neuroimaging projects of the Center would directly benefit from this grant. A fourth project to be supported by the proposed instrument is in the field of mechanical and material engineering. The central objective of the CVCVBM is to develop the technology to support multimodal fusion of brain histological data. The specific focus is on the rat and mouse nervous system. The approach being developed involves computer algorithms to map experimental data into high-resolution, 20 m/voxel, 3D atlases. The proposed instrument would support both construction of the rat and mouse atlas and critical tests of the mapping algorithms. The fourth project discussed in this proposal examines bone remodeling activity in the vicinity of a new class of swelling type composite materials for orthopaedic implant application. Here, the critical feature offered by the Cryopolycut is its ability to section through untreated bone. The impact of the proposed infrastructure enhancement extends beyond these projects. The CVCVBM research program is an instrumentation development research program. Tools built at the Center are widely distributed to other laboratories. Success in construction of the multimodal fusion engine would likely enhance neurobiological research at l arge. Furthermore, the facilities at the center are open to the research community and the proposed instrumentation would compliment currently available shared equipment to support construction of other high resolution 3D digital atlases.