The goal of this proposal is to secure funding to add an Imaging Cryomicrotome to the Center for Molecular and Genomic Imaging, a core facility at UC Davis that provides the infrastructure and expertise to conduct in vivo imaging studies in animal models. We propose to purchase a Barlow Scientific Imaging Cryomicrotome (Olympia, WA) that includes a Computer Controlled Cryomicrotome (able to section a 12 x 12 x 24 cm rectangular solid in 40 um thick sections), Fluorescence Imaging System (including a Princeton Instruments ES-3200 CCD camera, Nikon F-mount lens, Cermax 300 watt xenon arc lamp and optical filters and wheels), Computer Hardware and Software to operate the system. The system takes successive cryomicrotome slices and, after a programmed number of slices, excites the block face of the tissue and records one or more images;since the block face is imaged, the images are automatically registered. The system enables fluorescence excitation with up to 5 wavelengths in the xenon arc lamp spectrum and imaging with up to 5 fluorescence wavelengths. Software reconstructs the location of the image source by deconvolving the images taken. The system will be placed in our core facility and used to support and aid NIH-funded research in diverse areas such as atherosclerosis, cancer, airway disease, targeted molecular imaging probe development, and validation of in vivo imaging technologies. The system will directly support the development of new targeted diagnostic and therapeutic strategies, as well as to characterize and better understand the molecular and biochemical basis of normal and diseased tissue in animal models of human disease. Public Health Relevance: The field of molecular imaging seeks to discover new approaches to imaging specific biologic targets and pathways in vivo, with the ultimate goal of providing patient-specific and molecularly-based diagnostic information. In addition, molecular imaging approaches are being developed to directly monitor molecularlytargeted therapies, cellular therapies and gene therapies. Fluorescent probes are a critical resource, as they can be used to label nanoparticles, liposomes, antibodies, peptides and enzyme substrates for in vivo and ex vivo study in animal models. The proposed imaging cryomicrotome instrument will be integrated in our center with existing 2D and 3D in vivo whole-body mouse fluorescence systems to provide a comprehensive resource for NIH-funded researchers to study the spatial and temporal distribution of fluorescent particles, molecules and reporter proteins in the whole animal at spatial resolutions ranging from tens of microns with this instrument, to a few mm with in vivo techniques. This provides a powerful platform for characterizing animal disease models and non-invasively determining the efficacy of new diagnostic and therapeutic strategies in preclinical models prior to translation to the clinic.