Visualizing Cortical Pore Space Constituents

描述(申请人提供)：皮质骨强度对骨骼完整性至关重要。皮质微结构，特别是孔隙率，对皮质的力学性能有很大影响。此外，皮质骨的微结构对疾病、治疗和代谢变化有反应。因此，皮质微结构的研究是了解骨骼内发生的生物学、病因学和生物力学过程的一个重要方面。导致皮质孔隙度增加的机制尚不清楚。我们的中心假设是，皮质孔隙空间的含量可能是孔隙扩张机制的一个指示器。毛孔内的骨髓可能表示皮质内的“小梁化”，或骨髓腔向皮质包膜扩张。孔隙内的血管和造血组分可能表明通过血管网络的合并或扩张而形成大的毛孔。从长远来看，表征孔隙组成和了解孔隙扩张机制可能有助于制定预防或逆转增加的孔隙率和相关的骨脆性的策略。这项研究的总体目标是开发一种活体可视化和量化皮质孔隙度和POR含量的技术，并将该技术应用于纵向数据集。我们将使用体内成像技术，特别是高分辨率外周定量计算机断层扫描(HR-pQCT)和磁共振(MR)成像来表征孔隙内容。HR-pQCT可实现皮质微结构的3D可视化。MR提供了脂肪和水分成分的3D可视化和区分。其具体目的是：i)开发和验证联合HR-pQCT和MR成像的孔隙含量表征，以及ii)联合HR-pQCT和MR成像定量孔隙度和孔隙含量的纵向变化。为了解决目标I，将在身体胫骨中使用常规和先进的MR技术进行HR-pQCT和MR的联合分析。将进行组织学分析，以确定通过成像确定的含有骨髓脂肪和血管成分的区域的孔隙内容物的组成。为了解决AIM II，将分析现有的纵向数据集，并将量化孔隙率的纵向变化以及皮质孔隙空间内骨髓脂肪和血管成分的分布。这项工作将在纵向环境下发展皮质孔隙成分的体内表征，并将为未来研究皮质孔隙率增加的机制的体内研究提供先进成像技术的初步数据。对皮质孔隙率增加的机制的识别将指导靶向治疗的发展，可能是通过成骨细胞治疗或抗血管生成治疗。

DESCRIPTION (provided by applicant): Cortical bone strength is critical to skeletal integrity. Cortical microstructure, in particular porosity, has a significant impact on mechanical properties of the cortex. Additionally, cortical bone microstructure is responsive to disease, therapy, and metabolic alterations. Therefore the investigation of cortical microstructure is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. The mechanisms driving increased cortical porosity are unknown. Our central hypothesis is that cortical pore space contents may be an indicator of pore expansion mechanisms. Marrow within a pore may indicate endocortical 'trabecularization', or an expansion of the marrow cavity into the cortical envelope. Vessel and hematopoietic components within pore space may indicate the formation of large pores via merging or expansion of the vascular network. In the long term, characterizing pore space constituents and understanding pore expansion mechanisms may aid in the development of strategies to prevent or reverse increased porosity and the associated bone fragility. The overall goal of this research is to develop a technique for in vivo visualization and quantification of cortical porosity and por content, and to apply this technique to a longitudinal data set. We will characterize pore content using in vivo imaging techniques, specifically high resolution peripheral quantitative computed tomography (HR-pQCT) and magnetic resonance (MR) imaging. HR-pQCT enables 3D visualization of cortical microstructure. MR provides 3D visualization and discrimination of fat and water components. The specific aims are to: I) develop and verify pore space content characterization by combined HR-pQCT and MR imaging and II) quantify longitudinal changes in porosity and pore space content by combined HR-pQCT and MR imaging. To address Aim I, combined HR-pQCT and MR analysis will be applied using both conventional and advanced MR techniques in cadaveric tibiae. Histological analysis will be performed to confirm the composition of pore space contents in regions determined by imaging to contain marrow fat and vascular components. To address Aim II, an existing longitudinal data set will be analyzed and longitudinal changes in porosity and distribution of marrow fat and vascular components within the cortical pore space will be quantified. This work will develop in vivo characterization of cortical pore constituents in a longitudinal setting, and will provide pilot data on advanced imaging techniques for future in vivo studies investigating mechanisms of increased cortical porosity. The identification of mechanisms of increased cortical porosity will direct the development of targeted treatments, possibly through osteoblastogenic or anti-angiogenic therapy.