The goal of this proposal is to secure funding to add an X-ray "microscope" to the Center for Molecular and Genomic Imaging, a core facility at UC Davis that provides centralized infrastructure and expertise to conduct imaging studies in animal models and biospecimens. We propose to purchase an Xradia microXCT-200 high- resolution X-ray tomography microscope system that includes a 90kV microfocus X-ray source, a 4 M pixel CCD sensor, selectable detector optics with magnifications ranging from 4X to 40X, and a workstation for reconstruction and display of the large CT datasets. The system will be used for high resolution imaging of a range of biospecimens from 3-D cell culture, animal model tissues and patient biopsy samples in applications that span imaging of calcifications in tumors and atherosclerotic plaques, imaging of bone and joint pathologies and regenerative therapies, evaluation of the 3-D structure and mechanical properties of biomaterials and scaffolds, and imaging of the distribution of high-density (e.g. gold) nanoparticles and nanorods, to name just a few. The proposed system can achieve a spatial resolution (10% MTF) of <1 ?m using the 40X optics and can image specimens up to 50 mm in size (20 mm with 40X detector). The system will be placed in our core facility and used to support and aid NIH-funded research in diverse areas such as musculoskeletal disease, atherosclerosis, cancer, regenerative medicine, biomaterials, nanodiagnostics and nanotherapeutics. The system will directly support improved understanding of disease through high-resolution, high contrast imaging of surgical or biopsy specimens from animal models of patients, the characterization of engineered implants, constructs and tissues, and the effects of a range of therapeutic strategies. PUBLIC HEALTH RELEVANECE: Imaging is a powerful technology for visualizing complex 3-D biological tissues and changes in these tissues that occur through disease. The proposed X-ray tomography microscope system utilizes advanced optics and phase contrast methods to achieve unprecedented resolution (~ 1 ?m) and high contrast images across large volumes of biological tissue without staining or sectioning, providing undistorted and highly quantitative images of tissue morphology. This allows entire biopsy specimens, or organs/tissues from animal models to be imaged, and a wide range of morphological parameters (e.g. cellularity, density, vascularity, microarchitecture) to be assessed across the entire specimen, something that cannot be done with optical techniques due to the high degree of light scatter within biological tissues. The proposed X-ray microscope will be integrated in our imaging center with existing 2D and 3D in vivo imaging systems to provide a comprehensive resource for NIH funded researchers to study animal models of disease using imaging techniques.