This proposal seeks funding to purchase a high-resolution desktop microtomographic imaging device (5CT35, Scanco USA, Southeastern, PA). There is an urgent and ongoing need for the ability to do fine structural analysis of hard tissues at Yale University. In 1999, the Yale Core Center for Musculoskeletal Disorders (YCCMD) was established through a P30 Core Center award from NIAMS. This Center was competitively renewed in 2004. The Center has as its mission the development and evaluation of animal models of musculoskeletal disorders. It is currently comprised of 43 members from Departments across the Medical Center and the University, including Medicine, Pediatrics, Surgery, Orthopaedics, Obstetrics & Gynecology, Pathology, Immunobiology, and Developmental Biology. Among these investigators are some of the most prominent scientists in the field of skeletal biology, many of whom have ongoing animal studies as part of their research programs. The YCCMD supports a Pilot Project program, which funds 2 new investigators each year to develop animal models for musculoskeletal disorders. In 2005, Yale was awarded a P50 Center Research Translation, the Yale Center for X-Linked Hypophosphatemic Rickets Research (YC- XLH). This translational award funds 2 large projects involving animal models: one to explore the role of FGF signaling in bone, and one to explore the role of phosphate in regulating the growth plate. In addition, the YC-XLH supports 3 Pilot projects annually that will begin in 2008. It is likely that these Pilot projects will include animal models of musculoskeletal disorders. Currently, the only method available at Yale to estimate bone mass in mice is PIXimus, operated by the Physiology Core of the YCCMD. There is no microCT machine at Yale University. Consequently, investigators requiring this technology have had to outsource their experiments, either to the University of Connecticut microCT facility run by Dr. Douglas Adams, or to Dr. Mary Bouxsein's facility in Boston. Since these machines are already heavily committed, samples from Yale receive lower priority at the collaborating institutions. The YCCMD's Histomorphometry Unit is being overwhelmed with samples in lieu of another methodology to separately determine cortical and trabecular bone mass or to provide detailed microarchitectural analysis of bone. The acquisition of the Scanco 5CT35 will give investigators at Yale state-of-the-art, high-resolution (3.5 micron) imaging capacity, as well as the ability to undertake finite element analysis. These capabilities are absolutely required to sustain the current pace of discovery in musculoskeletal science at Yale. ? ? ? ?