Osteoporosis and related metabolic bone diseases are nearly universal problems associated with advanced age, particularly for postmenopausal women, expecting to cost society over $22 billion annually by 2020, and leading to 65,000 deaths each year stemming from bone fragility fractures. Recent studies have demonstrated that MRI may be of particular utility for addressing several factors related to bone quality that can only be measured with difficulty in patients. High spatial resolution MRI can be used to accurately characterize trabecular microarchitecture, and follow it with treatment, without the attendant ionizing radiation dose of DXA or CT. Solid state MRI can uniquely measure the organic bone matrix content noninvasively as well as the mineral. Proton (1H) solid state MRI has been used to measure bone matrix, while phosphorus (31P) solid state MRI has potential to accurately assess 3D bone mineral density. Combining these two measurements in a single simultaneous measurement could facilitate a more informative diagnostic for metabolic bone disease, especially if coupled with high spatial resolution 3D trabecular imaging. MRI is an expensive measurement, and not justified for screening for or diagnosing metabolic bone disease. However, if the cost of MRI could be drastically reduced, such measurements could become financially competitive with DXA while providing significantly increased diagnostic information content, and at the same time completely eliminating ionizing radiation exposure. In this project, we will develop the methodology of MRI characterization of metabolic bone disease using a unique dedicated inexpensive, compact, cryogen-free extremity MRI scanner designed and constructed in a previous NIH-funded project. Notably, the magnet of this scanner has been designed for comfortable and efficacious extremity scanning, and in particular contains three bores: a central bore that is the “active” bore in which the limb being scanned is inserted, and two peripheral “nonactive” bores that comfortably accept the leg not being scanned. Both the capital and operating costs of this scanner, as well as the clinic “real estate” it occupies, are drastically lower than for the typical whole body scanner. As of this writing, a second generation compact tiltable magnet with multiple openings may arrive in the PI's lab by the beginning of this project. The specific aims are: 1) Further the technical development of high spatial resolution 3D MRI of trabecular network architecture, and solid state proton and phosphorus MRI for quantitative bone mineral and matrix measurement; 2) Assess the quantitative accuracy of solid state MRI for these measurements in phantoms, animal tissues, and live animals; 3) Evaluate the repeatability and accuracy of high spatial resolution and solid state MRI scanning in healthy volunteer subjects; and 4) Carry out studies of metabolic bone disease patients and age- and gender-matched normals to make a preliminary ass...