Project Summary / Abstract Osteoporosis (OP) is a degenerative skeletal disease which affects an estimated 200 million people worldwide including 30% of all postmenopausal women in the United States and Europe. Hip fractures are the second most common type of OP fracture and cause the greatest mortality and morbidity of all OP fractures, with the one- year mortality rate reaching 20%. Clinical assessment of fracture risk is made via bone densitometric techniques such as dual-energy X-ray absorptiometry (DXA) or quantitative Computed Tomography (QCT), however, these methods are poor predictors of hip fractures with sensitivities of less than 50%. There is thus a need to develop adjunctive, novel, and accurate methods for non-invasively assessing bone quality to better inform clinical treatment of osteoporosis and to enable new research discoveries in bone pathophysiology. The proposed work builds on recent research conducted in the applicant’s lab based on magnetic resonance imaging (MRI) ultrashort echo time (UTE) pulse sequences for assessing bone material composition. I propose to develop and validate a protocol for mapping bone susceptibility in the proximal femur in vivo. First, I will evaluate the efficacy of regularization and deep learning methods for computing the ill-posed dipole inversion through comparisons in cadaveric femora specimens with the gold standard susceptibility method, Calculation of Susceptibility through Multiple Orientation Sampling. Next, I will investigate the extent to which magnetic susceptibility is related to bone health through validation experiments with other imaging biomarkers and with whole bone mechanical testing that mimics a sideways fall. Finally, I will assess the clinical feasibility of bone susceptibility by tracking longitudinal changes following treatment in a small cohort of postmenopausal women. Susceptibility measurement reproducibility and associations with DXA will also be quantified. I anticipate that the results of this study can lead to a clinically feasible approach to measure bone health beyond what is currently possible and could assist in future pharmaceutical or pathophysiological studies of bone diseases.