Structural MRI of trabecular bone for therapy response monitoring

描述（由申请人提供）：骨质疏松症的主要表现是发生骨折。大多数骨质疏松性骨折发生在骨小梁丰富的骨骼部位。其中主要是椎骨，手腕和股骨近端。髋部骨折在发病率和死亡率方面是最令人衰弱的腰椎骨折。现在有强有力的证据表明，骨质量的损失伴随着骨小梁网结构完整性的下降。继发于性腺类固醇耗竭的机械能力受损是由骨结构组成的拓扑变化引起的，其中主要是小梁板的开窗导致其转化为杆和杆的最终破坏。作为抗吸收治疗的补充，最近已经有新的疗法可用于用骨形成（即合成代谢）药物治疗严重骨丢失的破坏性后果。然而，目前尚不清楚这些治疗是否真的能够逆转小梁网的崩解，以及结构变化与抗吸收治疗诱导的结构变化有何不同。在这个项目中，我们建议开发新的基于微MRI的技术，适用于量化代谢性骨病患者各种治疗形式的结构和机械后果。我们的目的是将这种方法应用于骨折高危患者，并使用1-34甲状旁腺激素或阿仑膦酸钠治疗。总的假设是，新的方法将提供详细的了解骨小梁的结构表现进行短期药物治疗。该项目将包括六个具体目标，涉及数据采集和重建、运动校正、低温射频线圈技术、图像处理和分析以及基于图像的骨力学有限元建模等新方法的开发、集成和评估。能力。我们计划通过分包合同与两个外部合作者（休斯顿大学德克萨斯超导中心电气工程系的Jarek Wosik博士和哥伦比亚大学生物医学工程系的Edward Quo博士）合作实现这些目标。已经建立的宾夕法尼亚大学内部与查尔斯爱泼斯坦博士（数学系）和彼得斯奈德博士（医学系，内分泌科）的伙伴关系将进一步扩大和加强。

DESCRIPTION (provided by applicant): The chief manifestation of osteoporosis is the occurrence of fractures. Most osteoporotic fractures occur at skeletal locations rich in trabecular bone. Prevailing among these are the vertebrae, wrist and proximal femur. Hip fractures are the most debilitating among osteoporotic fractures in terms of morbidity and mortality. There is now strong evidence that the loss of bone mass is accompanied by a decline in the trabecular bone net- work's structural integrity. The impaired mechanical competence secondary to gonadal steroid depletion is caused by topological changes in the bone's architectural make-up, chief among which is fenestration of tra becular plates resulting in their conversion to rods and the latter's eventual disruption. Complementing antire- sorptive treatment, new therapies have recently become available to treat the devastating consequences of severe bone loss with bone-forming (i.e. anabolic) drugs. It is not clear, however, whether such therapies are, in fact, able to reverse the disintegration of the trabecular network, and to what extent the structural changes differ from those induced by antiresorptive treatment. In this project we propose to develop novel micro-MRI-based technology suitable to quantify the structural and mechanical consequences of various forms of treatment of patients with metabolic bone disease. We aim to apply this methodology to patients who are at high risk of fracture and who are treated either with 1-34 parathyroid hormone or alendronate. The overall hypothesis is that the new methodology will provide detailed insight into the structural manifestations of trabecular bone subjected to short-term drug treatment. The project will consist of six specific aims involving the development, integration and evaluation of new methods involving data acquisition and reconstruction, motion correction, cryogenic RF coil technology, image processing and analysis, as well as image-based finite-element modeling of bone mechanical competence. We plan to address these goals in partnership with two external collaborators through subcontracts (Dr. Jarek Wosik, Department of Electrical Engineering, Texas Center for Superconductivity, University of Houston, and Dr. Edward Quo, Department of Biomedical Engineering, Columbia University). Already established Penn-internal partnerships with Dr. Charles Epstein (Department of Mathematics) and Dr. Peter Snyder (Department of Medicine, Division of Endocrinology) will be further expanded and strengthened.