Summary/Abstract An essential question for studies of musculoskeletal biology is: Did the intervention result in more or less tissue? Assessing the amount of tissue and its distribution (morphology) requires 3D imaging. The gold standard for imaging in small animal models is micro-computed tomography (CT), which relies on differential attenuation of x-ray energy to provide image contrast, and is capable of high resolution (1-10 micron). MicroCT is ideally suited for bone imaging, and its use for quantifying bone morphology is essential to skeletal researchers. In addition, microCT is an underutilized modality for quantitative, high-resolution imaging of non- mineralized musculoskeletal tissues (cartilage, tendon, disc, muscle), provided that suitable x- ray attenuating contrast agents are used. We propose to purchase a Scanco uCT 50 cabinet, cone-beam microCT system to support high-resolution 3D imaging of musculoskeletal tissue specimens. This is a commercially available, state-of-the-art imaging system for non- destructive, high-resolution, 3D x-ray CT. The system is user-friendly and capable of high throughput due to a large x-ray detector and an integrated multiple sample changer, along with a powerful computer cluster. We will utilize the new instrument for imaging both bone and non- mineralized tissues in the following four applications: 1) Intact Bone; 2) Bone Healing; 3) Bone Pathological Defects; and 4) Non-Mineralized Musculoskeletal Tissues. We have assembled a group of 8 Major and 8 Minor Users who have a track record of utilizing microCT imaging – this new instrument is essential to advance their research projects. These users are supported by 30 current NIH research grants from six institutes (NCI, NIA, NIDCR, NIDDK, NIAMS and NINDS), totaling $7.1 million direct costs/year. Thus, the instrument will have a broad benefit across multiple research programs relevant to osteoporosis, arthritis, osteomyelitis, degenerative disc disease, fracture repair and cancer. The instrument will be located in the Washington University Musculoskeletal Research Center (MRC), and managed through the existing Musculoskeletal Structure and Strength Core. In conclusion, the system acquired through this shared instrumentation grant will have an immediate and sustained benefit to biomedical research at Washington University.