Osteoporosis Treatment Response Assessed by Micromechanical Modeling of MRI Data

通过 MRI 数据的微机械模型评估骨质疏松症治疗效果

• 批准号: 7494109
• 负责人: Felix W Wehrli
• 金额: $ 30.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494109
• 关键词: Address; Age; Agreement; Algorithms; Architecture; Behavior; Biological Preservation; Biopsy; Bone Density; Bone plates; Clinical Trials; Competence; Complement; Condition; Data; Data Set; Development; Dialysis procedure; Disease Progression; Disease regression; Distal; Dose; Eating; Elements; End Point; End stage renal failure; Enrollment; Estrogens; Event; Failure; Finite Element Analysis; Fracture; Funding; Glucocorticoids; Gold; Human; Image; Incidence; Individual; Kidney Transplantation; Laboratories; Labyrinth fenestration; Magnetic Resonance Imaging; Maintenance; Measurable; Measurement; Measures; Mechanical Stimulation; Mechanics; Methods; Modeling; Motion; Noise; Numbers; Osteoporosis; Osteoporosis prevention; Outcome Measure; Pathologic Processes; Patients; Pharmaceutical Preparations; Physical Dialysis; Play; Postmenopause; Process; Relative (related person); Research; Research Personnel; Resolution; Role; Scanning; Schedule; Signal Transduction; Simulate; Specific qualifier value; Specimen; Standards of Weights and Measures; Structure; Study Subject; System; Techniques; Testing; Testosterone; Three-Dimensional Image; Three-Dimensional Imaging; Treatment Efficacy; Woman; Work; X-Ray Computed Tomography; base; bone; cohort; cost; design; follow-up; image processing; image registration; improved; in vivo; indexing; insight; men; peer; radius bone structure; response; retinal rods; simulation; size; substantia spongiosa; tibia; treatment effect; virtual

DESCRIPTION (provided by applicant): New powerful drugs for treatment and prevention of osteoporosis are already available or are currently under development. The primary endpoint for these studies continues to be fracture incidence, the secondary endpoint typically is bone mineral density (BMD), both of which are fraught with problems. The former requires a very large number of study subjects as fractures are relatively rare events and require long observation periods, therefore resulting in excessive costs and long development cycles. BMD has been an unreliable indicator of treatment efficacy showing often disproportionately small increases relative to the extent of fracture reduction caused by the drug, in contrast to the much larger architectural changes that occur in the trabecular bone (TB) network. Progress in 3D high-resolution MRI (¿-MRI) now allows acquisition of images from which the topology of the TB network can be established. Nevertheless, in spite of these advances, structure plays only a surrogate role and it is not known which parameters and combinations thereof are optimal in terms of responding to treatment, and which are most representative of strength. Advances in micromechanical modeling now permit micro finite-element (¿-FE) computations of TB mechanical competence, potentially providing insight into the mechanical implications of disease progression and regression. We have, in preliminary work, examined the feasibility of quantifying the effect of antiresorptive treatment in a small cohort of patients and demonstrated significant improvement in the elastic moduli after computing the full stiffness matrix on the basis of MR images acquired in the distal tibia. While encouraging, the feasibility of deriving mechanical parameters from in vivo images as possible end points in clinical trials demands further scrutiny. In this project we advance the hypothesis that the treatment-induced changes in the bone's mechanical parameters, estimated from ¿-FE calculations on the basis of in vivo ¿-MRI, represent a quantitative measure of treatment response. The proposed research, involving four specific aims, seeks to (1) further develop algorithms for processing in vivo ¿-MRI data with improved motion correction and serial registration capabilities; (2) evaluate the effect of resolution and noise on the derived mechanical indices in images of intact specimen under conditions of in vivo ¿-MRI as well as by simulation previously or currently in progress to determine the effect of treatment and comparing the mechanical with of specimen ¿-CT images; (4) apply ¿-FE analysis to three longitudinal ¿-MRI studies performed structural indices.

描述（由申请人提供）：用于治疗和预防骨质疏松症的新型强效药物已经上市或正在开发中。这些研究的主要终点仍然是骨折发生率，次要终点通常是骨矿物质密度（BMD），两者都充满了问题。前者需要大量的研究对象，因为骨折是相对罕见的事件，需要较长的观察期，因此导致成本过高，开发周期长。BMD是一个不可靠的治疗疗效指标，相对于药物引起的骨折复位程度，BMD的增加往往不成比例地小，而骨小梁（TB）网络中发生的结构变化要大得多。3D高分辨率MRI（？-MRI）的进展现在允许采集图像，从中可以建立TB网络的拓扑结构。然而，尽管有这些进展，结构仅起替代作用，并且不知道哪些参数及其组合在对治疗的响应方面是最佳的，以及哪些参数最能代表强度。微机械建模的进展现在允许TB机械能力的微观有限元（<$-FE）计算，可能提供对疾病进展和消退的机械影响的洞察。在初步工作中，我们研究了在一小群患者中量化抗骨吸收治疗效果的可行性，并证明了在胫骨远端采集的MR图像基础上计算完整刚度矩阵后弹性模量的显著改善。 虽然令人鼓舞的是，在临床试验中从体内图像中获得机械参数作为可能的终点的可行性需要进一步审查。在这个项目中，我们提出了一个假设，即治疗引起的骨力学参数的变化，估计从<$-FE计算的基础上，在体内<$-MRI，代表治疗反应的定量测量。拟议的研究，涉及四个具体目标，旨在（1）进一步开发用于处理体内<$-MRI数据的算法，具有改进的运动校正和序列配准能力;（2）评估分辨率和噪声对在体内<$-MRI条件下完整标本图像中导出的机械指数的影响。-MRI以及通过先前或当前正在进行的模拟来确定治疗的效果，并将样本的力学与CT图像进行比较;（4）将FE分析应用于三个纵向的CT图像。-MRI研究进行结构指数。