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、手腕和股骨近端。就发病率和死亡率而言，髋部骨折是骨质疏松性骨折中最令人衰弱的。现在有强有力的证据表明，骨量的丧失伴随着骨小梁网络结构完整性的下降。继发于性腺类固醇耗竭的机械能力受损是由骨骼结构组成的拓扑变化引起的，其中最主要的是小梁板的开窗，导致它们转化为杆状，最终导致后者的破坏。作为抗吸收治疗的补充，最近出现了新的治疗方法，用成骨(即合成代谢)药物治疗严重骨丢失的破坏性后果。然而，目前尚不清楚这种疗法是否确实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有多大不同。在这个项目中，我们建议开发新的基于Micro-MRI的技术，适用于量化代谢性骨病患者各种形式治疗的结构和机械后果。我们的目标是将这一方法应用于骨折风险较高且接受1-34甲状旁腺激素或阿伦磷酸钠治疗的患者。总体假设是，新的方法将提供对接受短期药物治疗的松质骨的结构表现的详细洞察。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骼机械能力有限元建模等新方法的开发、集成和评估。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Jarek Wosik博士和哥伦比亚大学生物医学工程系Edward Quo博士)合作实现这些目标。宾夕法尼亚大学--与查尔斯·爱泼斯坦博士(数学系)和彼得·斯奈德博士(内分泌科医学系)的内部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.