Micro-Mechanical Modeling of Trabecular Bone

描述（由申请人提供）：在过去的资助周期中，NIH生物工程研究基金（BRG）的目标是开发一种新的骨小梁形态学和微观力学建模方法，该方法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）。克服巨大的技术挑战，我们已经成功地开发了新的个体骨小梁分割（ITS）的基础上形态和高效的板-杆（P-R）建模技术，自动分割成单独的骨小梁板和杆的骨小梁微结构。在这个竞争性的继续应用中，我们建议将我们新的生物工程ITS技术转化为整个人骨的基础科学和计算。我们建议（1）研究全身椎体塌陷的生物力学，这将改善椎体骨折的临床定义，（2）开发整个胫骨远端和桡骨骨段的计算效率高的患者特异性P-R模型，这将把我们的研究结果转化为临床HR-pQCT研究，（3）建立胫骨远端/桡骨和椎体之间ITS显微结构测量的关系。 我们将在此竞争性继续申请中实现以下具体目标：具体目标1：开发整个椎体的基于ITS的P-R有限元模型;通过与直接实验和基于体素的椎体有限元模型的强度测量值进行比较，验证这些高效的椎体特异性模型在预测强度方面的有效性;并使用基于ITS的P-R模型模拟确定骨小梁密度、类型和方向在整个椎体塌陷中的作用。具体目标二：为整个胫骨远端和桡骨节段开发基于ITS的HR-pQCT图像P-R模型，并通过与直接实验和基于体素的胫骨远端或桡骨有限元模型的强度测量值进行比较，验证这些高效的患者特定模型在预测强度方面的有效性。具体目标3：将使用HR-pQCT图像的胫骨远端和桡骨的整个松质骨段的基于ITS的测量与来自相同尸体供体的椎骨的<$CT的测量进行比较。 该研究将把ITS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、高效的骨强度评估工具。此外，我们还将建立周围骨骼（桡骨和胫骨）与中央骨骼（椎骨）之间的微观结构和生物力学联系，从而有助于骨质疏松症和骨折发病机制的研究。

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.