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3-D Visualization and Prediction of Vertebral Fractures

椎骨骨折的 3D 可视化和预测

基本信息

批准号：
10681728
负责人：
Elise F Morgan
金额：
$ 5.25万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-07 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10681728
关键词：
Address Adult Affect Age Aging Biochemical Biological Assay Biomechanics Bone Density Bone Tissue Cadaver Cartilage Characteristics Clinical Collagen Coupled Data Dependence Diagnostic Elderly Elements Failure Fracture Future Goals Health Human Image Incidence Intervertebral disc structure Magnetic Resonance Imaging Measurement Measures Mechanics Mediating Methods Minerals Modeling Modulus Osteoporosis Outcome Pathogenesis Patients Performance Persons Prevention Process Property Publishing Resolution Rest Risk Risk Factors Scanning Specimen Spinal Fractures Stress Structure Surface Testing Thick Time Tissues Treatment Protocols Vertebral column Woman X-Ray Computed Tomography age related aging population base bone compliance behavior crosslink density diagnostic tool ductile experimental study fracture risk high risk image guided improved innovation interdisciplinary approach intervertebral disk degeneration mechanical behavior mechanical properties men microCT novel pre-clinical predictive tools simulation spine bone structure substantia spongiosa three-dimensional visualization

项目摘要

Vertebral fractures (VF) afflict more than 25% of people over age 50, and their burden is growing. Current approaches for estimating VF risk, which rely heavily on measurement of the average bone mineral density (BMD) in the vertebra, are known to be insufficient, but the search for better diagnostics is hindered by poor understanding of the pathogenesis of VF. Increasing evidence suggests that the risk, mechanisms, and outcomes of VF depend critically on the interaction of tissues near the interface between the vertebra and the intervertebral disc. This endplate region is defined as the cartilage endplate (CEP), the bony endplate (BEP), and the subchondral trabecular bone (STB). The disc mediates how the net force borne by a given vertebra is distributed over the surface of the endplate (“endplate loading”), and the endplate region mediates how this force distribution is transferred to the rest of the vertebra. The mechanical behaviors of the disc and endplate region are therefore expected to affect when and how the vertebra fails. Indeed, we have found that VF in elderly vertebrae commonly initiate within the endplate region, and that the way this region fails is influenced by not only the microstructure of this region but also the extent of degeneration in the adjacent disc. Moreover, recent data suggest that the mechanical behavior of the endplate region may change with aging and disc degeneration in ways that are not well predicted by the average BMD of the vertebra. These collective findings reveal a paradigm in which delineation of the biomechanical interactions between the endplate region and disc holds an important key to identifying risk factors for VF and, consequently, to reducing the incidence and burden of VF. As such, the overall goal of this project is to define how degeneration and aging of the disc and endplate region influence the mechanisms of VF. Aim #1 will quantify the dependence of endplate loading on disc degeneration and will use non-invasively obtained estimates of endplate loading to develop accurate, patient-specific, finite element (FE) simulations of VF. This Aim will capitalize on recent advances in magnetic resonance imaging (MRI)-based assessments of the disc to achieve a novel integration of the state-of-the-art in clinically feasible FE models of the disc and vertebra. Aim #2 will address the current paucity of data on the biomechanics of the endplate region. Using mechanical testing, µFE modeling and biochemical assays, we will identify the extent to which properties such as the brittleness of the BEP, strength of the STB, and stiffness of the CEP change with age and disc degeneration. Aim #3 will focus on the way in which the endplate region fails during VF. Motivated by clinical and pre-clinical observations that disc health declines more rapidly following VFs that involve fracture of the BEP, as opposed to those that involve failure of only the STB, we will use both experiment and large-scale µFE models to identify characteristics of the disc and endplate region that are associated with BEP fracture. Altogether, these three Aims constitute a mechanistic, innovative, and interdisciplinary approach that will enable a step change in the understanding, prevention, and treatment of VF.

超过 25% 的 50 岁以上人群患有椎骨骨折 (VF)，而且他们的负担还在不断增加。当前的估计室颤风险的方法在很大程度上依赖于平均骨矿物质密度的测量众所周知，椎骨中的骨密度（BMD）是不够的，但对更好的诊断方法的探索却因质量不佳而受到阻碍。了解 VF 的发病机制。越来越多的证据表明，风险、机制和 VF 的结果主要取决于椎骨和椎骨之间界面附近组织的相互作用椎间盘。该终板区域被定义为软骨终板（CEP）、骨终板（BEP）、和软骨下小梁骨（STB）。椎间盘调节给定椎骨承受的净力如何分布在终板表面（“终板负载”），并且终板区域调节这种情况力分布转移到椎骨的其余部分。盘和端板的机械性能因此，预计该区域会影响椎骨失效的时间和方式。事实上，我们发现 VF 老年椎骨通常在终板区域内开始，并且该区域的失效方式受到影响不仅取决于该区域的微观结构，还取决于相邻椎间盘的退变程度。而且，最近的数据表明，终板区域的机械行为可能会随着老化和椎间盘的变化而改变。椎骨的平均 BMD 无法很好地预测退化的方式。这些集体发现揭示了一种范式，其中描绘了终板区域和椎间盘之间的生物力学相互作用掌握识别 VF 危险因素的重要关键，从而减少 VF 的发生率和 VF 的负担。因此，该项目的总体目标是定义椎间盘的退化和老化如何和终板区域影响VF的机制。目标#1将量化终板负载的依赖性椎间盘退变，并将使用非侵入性获得的终板负载估计来开发准确的、针对特定患者的 VF 有限元 (FE) 模拟。该目标将利用磁学的最新进展基于磁共振成像 (MRI) 的椎间盘评估，实现最先进技术的新颖整合在临床上可行的椎间盘和椎体有限元模型中。目标 #2 将解决当前缺乏数据的问题终板区域的生物力学。使用机械测试、μFE 建模和生化检测，我们将确定 BEP 的脆性、STB 的强度和刚度等特性的程度 CEP随着年龄和椎间盘退变而变化。目标 #3 将重点关注终板区域的方式 VF 期间失败。受临床和临床前观察的启发，椎间盘健康状况下降得更快在涉及 BEP 损坏的 VF（与仅涉及 STB 故障的 VF 不同）之后，我们将使用实验和大型 µFE 模型来识别椎间盘和终板区域的特征与 BEP 骨折有关。总而言之，这三个目标构成了机械性、创新性和跨学科方法将使 VF 的理解、预防和治疗发生重大变化。