Micro-Mechanical Modeling of Trabecular Bone

描述(申请人提供)：美国国立卫生研究院生物工程研究基金(BRG)在过去的资助周期中的目标是开发一种新的基于人类骨小梁样本的微计算机断层扫描(CT)和微磁共振图像(MRI)的数字拓扑分析(DTA)的骨小梁形态和微观力学建模方法。克服了巨大的技术挑战，我们成功地开发了基于形态和高效板棒(P-R)建模的新型个体骨小梁分割(ITS)技术，将骨小梁微结构自动分割成个体骨小梁和骨小梁棒状结构。在这项竞争性的延续申请中，我们建议将我们的新生物工程ITS技术转化为整个人类骨骼的基础科学和计算。我们建议(1)研究全身椎体塌陷的生物力学，这将提高临床对椎体骨折的清晰度；(2)建立计算高效的、针对患者的整个胫骨远端和桡骨骨段的P-R模型，将我们的研究成果转化为临床HR-pQCT研究；(3)在其微观结构测量中建立胫骨/桡骨远端与椎体之间的关系。我们将在这项竞争性延续应用中实现以下具体目标：具体目标1：开发基于ITS的整个椎体CT图像的P-R有限元模型；通过与直接实验的强度测量和基于体素的椎体有限元模型进行比较，验证这些高效的标本特定模型在预测强度方面的作用；以及使用基于ITS的P-R模型模拟确定松质骨密度、类型和方向在整个椎体塌陷中的作用。具体目标2：建立基于ITS的胫骨远端和桡骨远端HR-pQCT图像的P-R模型，并通过与直接实验的强度测量和基于体素的胫骨或桡骨远端有限元模型的比较，验证这些针对患者的高效模型在预测强度方面的有效性。具体目标3：利用HR-pQCT图像对胫骨远端和桡骨的整个骨小梁节段进行ITS测量，并与相同身体供体的椎骨CT测量结果进行比较。这项拟议的研究将把其分析技术转化为一种新的骨质疏松性椎体骨折发病机制的研究，并为临床研究开发一种准确和高效的骨强度评估工具。此外，我们还将在周围骨骼(桡骨和胫骨)和中央骨骼(椎骨)之间建立微观结构和生物力学联系，以帮助从机制上研究骨质疏松和骨折的发病机制。 与公共健康相关：这项竞争性延续申请建议将基于个体小梁分割(ITS)的新型形态和建模技术转化为脊椎骨折的生物力学发病机制，开发一种准确高效的全骨生物力学分析工具，用于临床研究，使用高分辨率外周定量断层扫描，并在附件和中央骨骼部位之间建立微观结构和生物力学关系。

DESCRIPTION (provided by applicant): The goal of this NIH Bioengineering Research Grant (BRG) in the past funding cycle was to develop a novel morphological and micro-mechanical modeling method for trabecular bone based on digital topological analysis (DTA) of micro-computed tomography (¿CT) and micro magnetic resonance images (¿MRI) of human trabecular bone samples. Overcoming great technical challenges, we have successfully developed novel individual trabecula segmentation (ITS) based morphological and highly efficient plate-rod (P-R) modeling techniques, which automatically segment trabecular bone microstructure into individual trabecular plates and rods. In this competitive continuation application, we propose to translate our novel bioengineering ITS techniques to whole human bone basic science and computation. We propose to (1) investigate biomechanics of whole body vertebral collapse, which will improve clinical definition of vertebral fractures, and (2) develop computationally efficient, patient-specific P-R models of whole distal tibia and radius bone segments, which will translate our findings to clinical HR-pQCT research, and (3) establish relationships in ITS microstructural measures between the distal tibia/radius and vertebral body. We will the following specific aims in this competitive continuation application: Specific Aim 1: Develop ITS-based P-R finite element models of ¿CT images of whole vertebral bodies; validate these highly efficient specimen-specific models in predicting strength by comparison with strength measurements from direct experiments and voxel-based finite element models of vertebral bodies; and determine the roles of trabecular bone density, type, and orientation in whole vertebral collapse using ITS- based P-R model simulations. Specific Aim 2: Develop ITS-based P-R models of HR-pQCT images for whole distal tibia and radius segments and validate these highly efficient patient-specific models in predicting strength by comparison with strength measurements from direct experiments and voxel-based finite element models of distal tibiae or radii. Specific Aim 3: Compare ITS-based measures of whole trabecular bone segments of the distal tibia and radius using HR-pQCT images with those from ¿CT of vertebrae from same cadaveric donors. The proposed study will translate the technology of ITS analysis to the study of a novel pathogenesis of osteoporotic vertebral fractures and develop an accurate and highly efficient translational tool for assessing bone strength for clinical research. In addition, we wil also establish microstructural and biomechanical links between the peripheral skeleton (radius and tibia) and the central skeleton (vertebra) such that it will aid mechanistic studies of pathogenesis of osteoporosis and fracture. PUBLIC HEALTH RELEVANCE: This competitive continuation application proposes to translate the novel individual trabecula segmentation (ITS)-based morphological and modeling technology to examine biomechanical pathogenesis of vertebral fracture, develop an accurate and efficient whole bone biomechanical analysis tool for clinical research using high resolution peripheral quantitative tomography, and establish microstructural and biomechanical relationship between appendicular and central skeletal sites.