Visualizing Cortical Pore Space Constituents

描述（由申请人提供）：皮质骨强度对骨骼完整性至关重要。皮质微观结构，特别是孔隙率对皮质的力学性能有显著影响。此外，皮质骨微观结构对疾病、治疗和代谢改变有反应。因此，皮质微观结构的研究是理解发生在骨骼内的生物学、病理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，皮层孔隙空间内容物可能是孔隙膨胀机制的一个指标。骨髓孔内可能提示皮质内“小梁化”，或骨髓腔向皮质包膜扩张。孔隙空间内的血管和造血成分可能表明通过血管网络的合并或扩张形成了大孔隙。从长远来看，表征孔隙空间成分和理解孔隙膨胀机制可能有助于制定预防或逆转孔隙度增加和相关骨脆弱性的策略。本研究的总体目标是开发一种体内皮层孔隙度和孔隙度的可视化和量化技术，并将该技术应用于纵向数据集。我们将使用体内成像技术，特别是高分辨率外围定量计算机断层扫描（HR-pQCT）和磁共振（MR）成像来表征孔隙含量。HR-pQCT能够实现皮层微观结构的三维可视化。MR提供了脂肪和水成分的三维可视化和区分。具体目的是：1)通过HR-pQCT和MR联合成像开发和验证孔隙空间含量表征；2)通过HR-pQCT和MR联合成像量化孔隙度和孔隙空间含量的纵向变化。为了解决第一个目标，将结合HR-pQCT和MR分析，在尸体胫骨中使用传统和先进的MR技术。将进行组织学分析，以确认由成像确定的含有骨髓脂肪和血管成分的区域的孔隙空间内容物的组成。为了解决Aim II，将分析现有的纵向数据集，并量化皮质孔隙空间内孔隙度和骨髓脂肪和血管成分分布的纵向变化。这项工作将在纵向设置中发展皮层孔隙成分的体内特征，并将为未来研究皮层孔隙增加机制的体内研究提供先进成像技术的先导数据。皮质孔隙度增加的机制的识别将指导靶向治疗的发展，可能通过成骨细胞或抗血管生成治疗。

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.