Tensor Scale-based Methods for Assessment of Trabecular Bone Quality

描述（由申请人提供）：小梁骨（TB）是一个复杂的准随机网络相互连接的支柱和板。结核病不断地重塑以动态地适应它所受到的压力（沃尔夫定律）。在骨质疏松症中，骨形成和骨吸收之间的动态平衡被扰乱，导致骨质流失和结构恶化，两者都增加了骨折的风险。大多数骨质疏松性骨折发生在富含结核的部位（椎骨、桡骨、股骨近端）。骨的机械能力只能部分地由骨矿物质密度（BMD）的变化来解释，这导致了骨质量的概念，其中主要是建筑作为TB强度的决定因素。CT和MRI的最新进展现在可以在体内对结核病进行成像。然而，有限的信噪比排除了远小于TB厚度的体素尺寸，因此导致图像本质上是模糊的。因此，大多数传统的组织形态学方法来评估结核病的结构不适用体内决议制度。本文提出了一种新的形态计量指标——张量尺度（t-scale），通过体内成像来衡量结核病微建筑的质量，并设计了实验方案来评估基于t-尺度的结核病建筑测量的可重复性和灵敏度。此外，我们将研究它们在检测结核病结构变化以应对疾病或治疗进展方面的优势。t标度的基本原理是将椭球体拟合到局部结构上。t尺度的独特性质是椭球体的形状、方向和大小同时决定了小梁的拓扑结构（板与棒）、方向和规模。我们在这个项目中的主要目标是：(1)开发从结核病图像中计算基于t标度的建筑测量的方法，(2)评估基于t标度的测量的敏感性和可重复性，(3)检验t标度测量预测结核病标本实验生物力学参数的能力，(4)检验t标度测量的敏感性，通过体内MRI检测骨质疏松性结核病损失和抗吸收治疗的影响。所提出的方法将(1)消除二值化的需要，(2)表征拓扑，方向和规模，而不需要骨架化，(3)检测早期结核病结构变化，以响应治疗或疾病进展。中心假设是，新的参数对检测重塑效应更敏感，比传统的措施更可重复。新方法的灵敏度和可重复性将通过合成结核网络、微ct和来自尸体远端桡骨结核核的离体磁共振成像以及实验生物力学数据、完整标本和人类受试者的磁共振图像以及以前由美国国立卫生研究院资助的临床研究的患者数据来评估。我们的目标是将基于t量表的分析方法应用于纵向和横断面成像研究，以评估骨质量。公共卫生相关性：该项目将开发一种先进的技术，通过体内成像来评估小梁骨（TB）的质量，这将使早期发现结核病治疗或骨质疏松症等骨病的微结构变化。骨质疏松症是一个主要的公共健康威胁，仅在美国，估计就有1000万人（800万女性和200万男性）已经患有这种疾病，估计还有近3400万人骨量低，使他们患骨质疏松症的风险增加。本项目提出的技术将有助于在疾病的早期诊断患者，并常规监测其疾病状态或治疗效果。

DESCRIPTION (provided by applicant): Trabecular bone (TB) is a complex quasi-random network of interconnected struts and plates. TB constantly remodels to adapt dynamically to the stresses to which it is subjected (Wolff's Law). In osteoporosis, this dynamic equilibrium between bone formation and resorption is perturbed, leading to bone loss and structural deterioration, both increasing fracture risk. Most osteoporotic fractures occur at sites rich in TB (vertebrae, radius, proximal femur). Bone's mechanical competence can only be partly explained by variations in bone mineral density (BMD), which led to the notion of bone quality, chief among which is architecture as a determinant of TB strength. Recent advances in CT and MRI now allow imaging of TB in vivo. However, the limited SNR precludes voxel sizes much smaller than TB thickness, therefore resulting in images that are inherently fuzzy. Therefore, most conventional histomorphometric approaches to TB structure assessment are not applicable to in vivo resolution regime. This proposal introduces a new morphometric index called tensor scale (t-scale) to measure quality of TB micro architecture via in vivo imaging and designs experimental plans to evaluate reproducibility and sensitivity of t-scale-based TB architectural measures. Also, we will examine their strengths to detect TB architectural changes in response to disease or treatment progression. The fundamental principle of t-scale is to fit an ellipsoid to a local structure. The unique property of t-scale is that the ellipsoid's shape, orientation and size simultaneously determine the topology (plates vs. rods), orientation and scale of trabeculae. Our major goals in this project are - (1) to develop the methodology for computing t-scale-based architectural measures from TB images, (2) to evaluate the sensitivity and reproducibility of t-scale-based measures, (3) to examine t-scale measures' ability to predict experimental biomechanical parameters of TB specimens and (4) to examine the sensitivity of t-scale measures to detect the effects of osteoporotic TB loss and antiresorptive treatment via in vivo MRI. The proposed method will (1) obviate the need for binarization, (2) characterize topology, orientation and scale without the need for skeletonization and (3) detect early TB architectural changes in response to treatment or disease progression. The central hypothesis is that the new parameters are more sensitive to detecting remodeling effects and more reproducible than conventional measures. Sensitivity and reproducibility of the new method will be evaluated using synthetic TB networks, micro-CT and ex vivo MR imaging of TB cores from cadaveric distal radii along with experimental biomechanical data, MR images of intact specimens and of human subjects, and finally, patient data from clinical studies previously funded by the NIH. Our objective is to apply t-scale based analysis methods to longitudinal and cross-sectional imaging studies for assessing bone quality. PUBLIC HEALTH RELEVANCE: This project will develop an advanced technology for trabecular bone (TB) quality assessment via in vivo imaging which will enable early detection of TB micro-architectural changes in response to treatment or bone disease including osteoporosis. Osteoporosis is a major public health threat and in the U.S. only, 10 million individuals (eight million are women and two million are men) are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis. The technology proposed in the project will be helpful to diagnose patients at early stage of the disease and routinely monitor their disease status or effects of therapeutic treatments.