Project Summary The goal of this application is to replace an essential, 14 year old in-vivo microCT imaging system at the Seattle Children’s Research Institute (SCRI) with a state-of-the-art Bruker Skyscan 1272 high-resolution 3D ex- vivo microCT imaging system. This instrument is required to conduct a diversity of research projects, which require imaging both at large-scale (whole organisms/organs) and microscopic-scale. This imaging resource will support the activities of 11 major and 4 minor users focused on three cross-cutting research themes: (1) Genetic mutations underlying human congenital syndromes that affect multiple organs, (2) development and pathology of vasculature, (3) mechanisms of tissue regeneration after ischemic damage or injury, and (4) basic research in bone biology and remodeling. A portfolio of 18 funded and 4 pending NIH grants, as well as funding from other federal agencies like NSF currently supports these projects. This exciting new technology allow users to rake benefits from the technological improvements introduced to microCT imaging and sample preparation in the last decade. As shown in our pilot data, with the new ex-vivo system we will be able to image tissues with higher resolution, with better image quality and clarity compared to our current end-of-life instrument. Further, some of the listed projects involve tedious phenotypic screens, which have been hampered by the manual sample navigation and data acquisition with our existing system. With an automated sample changer and a control software that automatically determines the optimal settings, based specimen dimensions, the proposed equipment will help our users overcome these problems, and achieve higher analytical throughput, while obtaining better quality data. There is strong Institutional commitment for the instrument, including state-of-the-art imaging space, coverage of service contracts, maintenance personnel effort in at least the first 5 years, backed-up data storage, and 3-D image analysis resources. While SCRI and University of Washington investigators comprise the main user group, these instruments would be accessible to other investigators from allied institutions such as the Fred Hutchinson Cancer Research Center, Institutes for Systems Biology and others, creating a unique and valuable community resource for macroscopic-to- microscopic imaging. In addition, there is extensive imaging expertise present at the SCRI Center that will house and support the device (PI, Maga, Co-I, Shih and Yu). This will guide the proper use, time allocation and maintenance of the instrument. This imaging resource would immediately influence the productivity and innovation of ongoing work and will be critical in furthering the long-range objectives of the biomedical community in the greater Seattle area.