MRI-Based Assessment of Structural and Mechanical Implications of Osteoporosis

基于 MRI 的骨质疏松症结构和机械影响评估

• 批准号: 8238508
• 负责人: Felix W Wehrli
• 金额: $ 50.46万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8238508
• 关键词: Address; Advocate; Age; Anatomy; Architecture; Biomechanics; Biopsy; Bone Density; Cadaver; Clinic; Competence; Data; Deformity; Diagnosis; Distal; Dual-Energy X-Ray Absorptiometry; Elements; Estrogens; Evaluation; Failure; Finite Element Analysis; Fracture; Hip region structure; Housing; Human; Image; Imaging technology; Intervention; Ionizing radiation; Link; Location; Magnetic Resonance Imaging; Marrow; Measurement; Measures; Mechanics; Menopause; Methodology; Methods; Minority; Modality; Modeling; Noise; Osteoporosis; Partner in relationship; Patients; Peripheral; Pharmaceutical Preparations; Postmenopause; Predisposition; Procedures; Property; Protocols documentation; Radial; Recruitment Activity; Research Personnel; Resolution; Risk; Risk Factors; Signal Transduction; Site; Specimen; Structure; System; Technology; Test Result; Testing; Translational Research; Translations; Treatment Efficacy; United States; Variant; Vertebral Bone; Vertebral column; Woman; Work; base; bone; bone quality; bone strength; cohort; in vivo; insight; osteoporosis with pathological fracture; research study; skeletal; spine bone structure; substantia spongiosa; three-dimensional modeling; tibia; virtual

DESCRIPTION (provided by applicant): The disconnect between bone density and fracture susceptibility has spurred the search for other risk factors that cause compromised skeletal strength. The applicants of this proposal previously developed methods, based on quantitative MRI for assessing multiple measures of bone quality, including trabecular bone microstructure via a procedure referred to as virtual bone biopsy (VBB). The potential of this technology has been demonstrated in translational research studies showing that structural measures of bone quality are more strongly associated with osteoporotic fractures than areal BMD and that these structural measures are sensitive indicators of drug intervention efficacy in patients with impaired structural integrity. The critical missing link is the association between measures of structure and measures of strength such as stiffness and failure load. There are very few studies that have attempted to relate in vivo bone- structure derived mechanical estimates from micro-finite element (?FE) analysis, with actual fracture data. Whereas both, high-resolution CT and MRI, are suited for this purpose, MRI has substantial advantages over CT, besides being free of ionizing radiation, in that it has superior bone-to-marrow contrast; and most importantly, an installed base of over 10,000 units in the United States alone. In this project we advance the following hypotheses: 1) that FE-estimated parameters (whole-section stiffness and ultimate strength, and sub-volume trabecular bone elastic and shear moduli) derived from in vivo ?MR images at the distal tibia and radius, are associated with structural parameters expressing scale, topology and orientation at the measurement sites, with structural measures jointly explaining as much as 90% of the variation in the mechanical parameters; 2) that these associations are stronger than those involving bone volume fraction or BMD alone; 3) that the mechanical and structural parameters at the surrogate sites are correlated with vertebral structural and mechanical parameters evaluated ex vivo and vertebral deformity status in vivo. We propose to evaluate the above hypotheses by addressing the following specific aims: 1. We will validate the proposed method in specimens of the distal tibia and radius by performing mechanical testing and comparing the data with ?FE-derived estimates of elastic moduli derived from micro-CT and ?MR images as well as with those from vertebral bone of the same donors. 2. We will evaluate a cohort of postmenopausal women with a protocol consisting of acquisition of high- resolution 3D ?MRI of the distal tibia and radius, 3D BMD by pQCT at matching anatomic locations, MRI of the spine for vertebral deformity assessment, and DXA aBMD at the spine and hip. 3. We will derive structural and mechanical parameters at the two peripheral sites to test the above hypotheses by comparing ?FE-estimated parameters with measures of structure and BMD, and with vertebral deformity status. The proposed in vivo MRI study will provide new insight into the microstructural and mechanical implications of osteoporosis, thereby providing the basis for translation of the methodology to the clinic, which is the long-term objective underlying the project. PUBLIC HEALTH RELEVANCE: The relationship between measures of bone strength and architecture is not understood and only recently technology has become available in the form of high-resolution noninvasive imaging and micro-finite-element analysis to explore these associations. In this project we address the hypothesis that bone mechanical competence can be predicted on the basis of high-resolution MRI in human cadaver specimens comparing mechanical test results with computational biomechanics and apply the methodology to postmenopausal women at risk of fracture by comparing the structural and mechanical parameters with vertebral deformity status.

描述（由申请人提供）：骨密度和骨折易感性之间的脱节促使人们寻找导致骨骼强度受损的其他危险因素。该提案的申请人先前开发了基于定量MRI的方法，用于评估骨质量的多种测量，包括通过称为虚拟骨活检（VBB）的程序评估小梁骨微观结构。这项技术的潜力已经在转化研究中得到证实，表明骨质量的结构测量与骨质疏松性骨折的相关性比面积骨密度更强，并且这些结构测量是结构完整性受损患者药物干预效果的敏感指标。关键的缺失环节是结构测量和强度测量（如刚度和失效载荷）之间的关联。很少有研究试图将体内骨结构从微有限元(？FE)分析，结合实际断裂数据。尽管高分辨率CT和MRI都适合于此目的，但MRI除了没有电离辐射外，还具有比CT更大的优势，因为它具有更好的骨髓对比；最重要的是，仅在美国就安装了超过1万台。在本项目中，我们提出了以下假设：1)fe估计参数（全截面刚度和极限强度，亚体积小梁骨弹性和剪切模量）来源于体内？胫骨远端和桡骨的MR图像与表达测量部位的尺度、拓扑和方向的结构参数相关，结构措施共同解释了多达90%的力学参数变化；2)这些关联比仅涉及骨体积分数或骨密度的关联更强；3)替代位点的力学和结构参数与体外评估的椎体结构和力学参数以及体内椎体畸形状态相关。我们建议通过解决以下具体目标来评估上述假设：1。我们将在胫骨远端和桡骨标本中进行力学测试，并将数据与？弹性模量的有限元估计源自micro-CT和？核磁共振成像以及来自同一供体椎骨的图像。2. 我们将评估绝经后妇女的队列，其方案包括获取高分辨率3D ？胫骨远端和桡骨MRI，匹配解剖位置的pQCT三维骨密度，脊柱MRI评估椎体畸形，脊柱和髋部DXA aBMD。3. 我们将推导出两个外围地点的结构和力学参数，通过比较？fe通过测量结构和骨密度以及椎体畸形状态来估计参数。拟议的体内MRI研究将为骨质疏松症的微观结构和力学意义提供新的见解，从而为将方法转化为临床提供基础，这是该项目的长期目标。