Tensor Scale-based Methods for Assessment of Trabecular Bone Quality

描述(申请人提供)：骨小梁(TB)是由相互连接的支柱和钢板组成的复杂的准随机网络。结核分枝杆菌不断重塑，以动态适应其承受的压力(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破坏，导致骨丢失和结构恶化，两者都增加了骨折的风险。大多数骨质疏松性骨折发生在结核(椎骨、桡骨、股骨近端)丰富的部位。骨骼的机械能力只能通过骨密度的变化来部分解释，骨密度的变化导致了骨质量的概念，其中最主要的是建筑作为结核病强度的决定因素。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SNR排除了比TB厚度小得多的体素大小，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计量学方法不适用于体内分解机制。该方案引入了一种新的形态测量指标，称为张量尺度(t-Scale)，用于通过活体成像来衡量结核微结构的质量，并设计实验计划来评估基于t-Scale的结核微结构测量的重复性和敏感性。此外，我们还将检查它们的优势，以检测结核病在应对疾病或治疗进展时的结构变化。T尺度的基本原理是将椭球体与局部结构相匹配。T尺度的独特性质是椭球体的形状、取向和大小同时决定了小梁的拓扑(板状和棒状)、取向和尺度。我们在这个项目中的主要目标是：(1)开发从结核图像中计算基于t尺度的结构测量的方法，(2)评估基于t尺度的测量的敏感性和重复性，(3)检验t尺度测量预测结核标本实验生物力学参数的能力，以及(4)通过活体MRI检查t尺度测量的灵敏度，以检测骨质疏松结核丢失和抗吸收治疗的影响。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的变化，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，比传统测量方法更具重复性。新方法的敏感性和重复性将通过使用合成结核网络、身体远端半径结核核心的Micro-CT和体外MR成像以及实验生物力学数据、完整标本和受试者的MR图像，以及之前由NIH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尺度的分析方法应用于纵向和横断面影像研究，以评估骨质量。与公众健康相关：该项目将开发一种先进的技术，通过活体成像来评估骨小梁(TB)的质量，这将使人们能够及早发现结核病微结构的变化，以应对治疗或包括骨质疏松症在内的骨骼疾病。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)已经患有骨质疏松症，估计还有近3400万人骨量不足，使他们患骨质疏松症的风险增加。项目中提出的技术将有助于在疾病的早期阶段对患者进行诊断，并定期监测他们的病情或治疗效果。

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.