Imaging of Metabolic Bone Response due to Localized Mechanical Loading

项目摘要 骨是一种固有的动态组织，具有独特的识别和适应机械力的能力 以满足其功能需求。而骨骼负荷刺激骨重建， 为了修复骨基质中的微损伤，过度的骨力可能是病理性的， 骨和关节退化以及骨骼骨折。许多方法可以评估骨的长期影响 通过结构和矿物质密度的适应;然而，骨对负荷的急性反应仍然很差 明白影像学评估骨重建的这些急性变化仍然是一个重大挑战。的 这一建议的科学前提是发展一种新的方法来测量急性代谢 骨骼对外力的反应。 该提案旨在开发和验证一种新的方法，使用18F-NaF PET动力学摄取来研究 骨对机械负荷的急性血管和代谢反应。我们的具体目标是：（1）发展一个 信号恢复模型以从多次注射中分离18F-NaF摄取，（2）创建肌肉刺激模型 用于骨力的局部生成和简化测量，以及（3）评估 测量急性骨力和改变的18F-NaF动力学。 本课题的创新点在于采用一种新的方法， 18F-NaF吸收模型，以解释多次示踪剂注入和研究关系的框架 机械力和体内急性骨变化之间的关系。这是一种新颖的方法， 评估急性血管和代谢骨对机械力的反应。成功整合这 技术将为我们如何评估骨代谢对机械刺激的反应提供突破， 解决肌肉骨骼生理学和病理生理学的关键问题。

PROJECT SUMMARY Bone is an inherently dynamic tissue which is uniquely capable of recognizing and adapting to mechanical forces to meet its functional demands. While skeletal loading stimulates bone remodeling, which serves to adjust bone architecture and to repair microdamage in the bone matrix, excessive bone forces can be pathologic and initiate bone and joint degeneration and skeletal fractures. Numerous methods can evaluate long-term impacts of bone adaptation through structure and mineral density; however the acute response of bone to loading remains poorly understood. Imaging assessment of these acute changes in bone remodeling remains a major challenge. The scientific premise of this proposal is the development of a new method to measure the acute metabolic response of bone to external forces. This proposal aims to develop and validate a novel methodology to use 18F-NaF PET kinetic uptake to study the acute vascular and metabolic response of bone to mechanical loads. Our specific aims are to (1) develop a signal recovery model to isolate 18F-NaF uptake from multiple injections, (2) create a muscle stimulation model for localized generation and simplified measurement of bone forces and (3) evaluate the relationship between measured acute bone forces and altered 18F-NaF kinetics. The innovation of this project is a novel method to induce localized joint forces, expanded pharmacokinetic models of 18F-NaF uptake to account for multiple tracer injections and a framework to study the relationship between mechanical forces and acute bone changes in vivo. The significance of this is a novel method to assess the acute vascular and metabolic bone response to mechanical forces. Successful integration of this technology will provide a breakthrough in how we assess bone metabolism in response to mechanical stimuli to tackle key questions in musculoskeletal physiology and pathophysiology.