Structural MRI of trabecular bone for therapy response monitoring

描述（申请人提供）：骨质疏松症的主要表现是骨折的发生。大多数骨质疏松性骨折发生在骨小梁丰富的骨骼部位。其中最常见的是椎骨、腕骨和股骨近端。髋部骨折是骨质疏松性骨折中发病率和死亡率最高的。现在有强有力的证据表明，骨量的减少伴随着小梁骨网结构完整性的下降。性腺类固醇耗竭引起的机械能力受损是由骨结构结构的拓扑变化引起的，其中主要是骨筋膜板的开窗，导致其转化为棒骨，并最终破坏棒骨。作为抗吸收治疗的补充，最近出现了新的治疗方法，可以用成骨（即合成代谢）药物治疗严重骨质流失的破坏性后果。然而，目前尚不清楚这种疗法是否真的能够逆转小梁网络的解体，以及这种结构变化与抗吸收治疗引起的结构变化在多大程度上不同。在这个项目中，我们建议开发一种新的基于微核磁共振成像的技术，适合于量化代谢性骨病患者各种形式治疗的结构和机械后果。我们的目标是将这种方法应用于骨折高风险的患者，并接受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洞察小梁骨的结构表现受到短期药物治疗。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能力有限元建模等新方法的开发、整合和评估。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。与Charles Epstein博士（数学系）和Peter Snyder博士（内分泌科医学系）已经建立的宾夕法尼亚大学内部合作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.