Bone health assessment through magnetic susceptibility mapping

项目摘要/摘要 骨质疏松症(OP)是一种退行性骨骼疾病，全世界约有2亿人患病。 包括美国和欧洲30%的绝经后女性。髋部骨折排在第二位 常见的OP骨折类型，是所有OP骨折中死亡率和发病率最高的，其中一种- 年死亡率达20%。骨折风险的临床评估是通过骨密度测量技术进行的 例如双能X射线吸收法(DXA)或定量计算机断层摄影术(QCT)，然而，这些 方法对髋部骨折的预测效果不佳，敏感性低于50%。因此，有必要发展 辅助、新颖、准确的非侵入性骨质量评估方法，以更好地为临床提供信息 治疗骨质疏松症，并在骨病理生理学方面有新的研究发现。 这项拟议的工作建立在申请人实验室最近进行的基于磁共振的研究基础上 成像(MRI)超短回波时间(UTE)脉冲序列用于评估骨材料成分。我建议 开发并验证一种在活体内绘制股骨近端骨敏感性图的方案。首先，我会 评价正则化和深度学习方法计算病态偶极子反演的有效性 通过身体股骨标本与金标准感受法的比较，计算 通过多方向采样获得更高的易感性。接下来，我将调查磁化的程度 易感性与骨骼健康有关，通过与其他成像生物标志物的验证实验和与 模拟侧向坠落的全骨力学测试。最后，我将评估骨的临床可行性。 在一小部分绝经后妇女队列中跟踪治疗后纵向变化的易感性。 药敏测量的重复性和与DXA的相关性也将被量化。 我期望这项研究的结果可以引导出一种临床上可行的方法来测量骨骼健康。 什么是目前可能的，并可能有助于未来的药物或病理生理学的骨骼研究 疾病。

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.