Imaging of Metabolic Bone Response due to Localized Mechanical Loading

局部机械负荷引起的骨代谢反应的成像

基本信息

批准号：
10042719
负责人：
Feliks Kogan
金额：
$ 63.08万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-16 至 2024-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10042719
关键词：
Acute Affect Anatomy Architecture Arthritis Biomechanics Blood Vessels Bone Diseases Bone Matrix Bone remodeling Clinical Clinical/Radiologic Computer software Degenerative polyarthritis Detection Development Distal Early Diagnosis Electric Stimulation Electromyography Elements Ensure Environment Exercise Femur Force of Gravity Fracture Functional Imaging Functional disorder Gastrocnemius Muscle Generations Human Hybrids Image Injections Joints Kinetics Knee Knee bone Knee joint Lateral Leg MRI Scans Magnetic Resonance Imaging Measurable Measurement Measures Mechanics Medial Metabolic Methodology Methods Minerals Modeling Molecular Motion Muscle Musculoskeletal Musculoskeletal Physiology Orthopedics Osteogenesis Osteoporosis Pathologic Perfusion Physiologic calcification Physiological Physiology Population Positron-Emission Tomography Protocols documentation Reaction Recovery Reproducibility Signal Transduction Sodium Fluoride Stimulus Structure System Techniques Technology Time Tissues Tracer Work arthropathies biomechanical model bone bone imaging bone metabolism data acquisition density design experience imaging modality in vivo in vivo evaluation innovation interest internal control joint destruction kinetic model mechanical force mechanical load metabolic imaging novel novel strategies pharmacokinetic model pressure radiotracer repaired response simulation skeletal spatial relationship tibia tool uptake

项目摘要

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.

项目概要骨骼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。骨骼负荷刺激骨骼重塑，从而调整骨骼为了修复骨基质的微损伤，过度的骨力可能是病理性的并引发骨和关节退化以及骨骼骨折。有多种方法可以评估骨骼的长期影响通过结构和矿物密度进行适应；然而骨骼对负荷的急性反应仍然很差明白了。对骨重塑的这些急性变化的成像评估仍然是一个重大挑战。这该提案的科学前提是开发一种测量急性代谢的新方法骨对外力的反应。该提案旨在开发和验证一种新方法，使用 18F-NaF PET 动力学摄取来研究骨骼对机械负荷的急性血管和代谢反应。我们的具体目标是 (1) 开发信号恢复模型，用于从多次注射中分离 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）评估之间的关系测量急性骨力并改变 18F-NaF 动力学。该项目的创新点是一种诱导局部关节力、扩大药代动力学的新方法用于解释多次示踪剂注射的 18F-NaF 摄取模型以及研究这种关系的框架机械力和体内急性骨变化之间的关系。其意义在于提供了一种新颖的方法评估急性血管和代谢骨对机械力的反应。成功整合此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。