BONE FORMATION STUDIES BY MAGNETIC RESONANCE MICROSCOPY

通过磁共振显微镜进行骨形成研究

• 批准号: 7168814
• 负责人: KIMBERLEE POTTER
• 金额: $ 18.61万
• 依托单位: AMERICAN REGISTRY OF PATHOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168814
• 关键词: Accounting; Adverse effects; Affect; Appendix; Arts; Biocompatible Materials; Biological Models; Biology; Bioreactors; Bone Development; Bone Growth; Bone remodeling; Calvaria; Cells; Child; Clinical; Collagen; Condition; Country; Development; Diagnostic; Diagnostic Procedure; Disease; Elderly; Electron Microscopy; Elements; Expenditure; Fiber; Fracture Healing; Goals; Growth Factor; Harvest; Healthcare; Histocytochemistry; Histology; Image; Image Analysis; Implant; In Vitro; Institutes; Intervention; Invasive; Investigation; Ionizing radiation; Laboratories; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Mature Bone; Measures; Mechanics; Medical; Methodology; Microscopy; Minerals; Modeling; Monitor; Nuclear Magnetic Resonance; Optics; Organ Culture Techniques; Organism; Orthopedics; Osteoblasts; Osteogenesis; Osteoporosis; Pathology; Personal Satisfaction; Pharmacologic Substance; Phase; Positioning Attribute; Process; Process Measure; Protons; Range; Rate; Relaxation; Research; Research Personnel; Resolution; Roentgen Rays; Role; Scanning Transmission Electron Microscopy Procedures; Skeletal system; Spatial Distribution; Specimen; Spectrum Analysis; Study of magnetics; System; Techniques; Technology; Testing; Time; Tissues; Today; United States; Water; Woman; Work; X ray diffraction analysis; X-Ray Diffraction; X-Ray Tomography; aging population; base; bone; bone loss; chronic pain; density; design; expectation; in vivo; indexing; innovation; instrumentation; millimeter; novel; novel diagnostics; osteoporosis with pathological fracture; programs; repaired; response; tissue culture; tool; water diffusion

DESCRIPTION (provided by applicant): Many of the diseases affecting today's aging population involve the degeneration of critical skeletal elements, causing chronic pain and loss of mobility. Clearly there is a need to better understand the basics of skeletal biology and its disease pathologies. While skeletal changes during bone development (in children) or bone degeneration (in the elderly) can be studied with X-ray based techniques, these studies measure the mineral content alone and expose healthy subjects to ionizing radiation. What is required is an analytical technique that can non-invasively evaluate the changes that occur in skeletal tissues during skeletogenesis, fracture healing, bone growth into orthopaedic implants, and in response to pharmaceutical interventions. This application proposes a strategy whereby nuclear magnetic resonance (NMR) imaging can be used as a novel non-invasive, non-ionizing means of assessing vertebrate bone formation and repair, providing new measures of these processes and circumventing the invasive and ionizing character of current approaches. This objective will be achieved through the application of the following specific aims: 1) To investigate the efficacy of NMR imaging as a tool for assessing bone formation in a model system based on a hollow fiber bioreactor (HFBR) seeded with primary osteoblast cells; 2) To employ X-ray microtomography (XMT) to establish the ranges of mineral densities for which quantitative NMR parametric maps can be used as surrogate measures of mineral content during bone formation in a HFBR; 3) To employ FT-IR microspectroscopy to establish the range of collagen concentrations for which quantitative NMR maps of the magnetization transfer (MT) effect can be used as a surrogate measure of collagen content for bone formed in a HFBR; and 4) To apply quantitative NMR indices to monitor how collagen and mineral contents change during the bone formation process in a calvarial organ culture system. Our studies, if successful, will yield quantitative, surrogate measures, which can be applied spatially and temporally to monitor the efficacy of different orthopaedic biomaterials, growth factors, bioreactors designs, and mechanical loading conditions on the bone formation process in vitro. Our studies will also yield a novel, non-invasive approach to osteogenesis studies in vivo.

描述（由申请人提供）：影响当今人口老龄化的许多疾病都涉及关键骨骼元素的退化，导致慢性疼痛和活动能力丧失。显然，需要更好地了解骨骼生物学及其疾病病理学的基础知识。虽然可以使用基于 X 射线的技术来研究骨骼发育（儿童）或骨骼退化（老年人）期间的骨骼变化，但这些研究仅测量矿物质含量并将健康受试者暴露于电离辐射。我们需要的是一种分析技术，能够非侵入性地评估骨骼发生、骨折愈合、骨骼生长成骨科植入物以及对药物干预的反应期间骨骼组织中发生的变化。该申请提出了一种策略，核磁共振（NMR）成像可用作评估脊椎动物骨形成和修复的新型非侵入性、非电离手段，为这些过程提供新的测量方法，并规避电流的侵入性和电离特性。接近。这一目标将通过以下具体目标的应用来实现：1）研究核磁共振成像作为评估骨形成工具的功效，该模型系统基于接种原代成骨细胞的中空纤维生物反应器（HFBR）； 2) 采用 X 射线显微断层扫描 (XMT) 确定矿物质密度范围，其中定量 NMR 参数图可用作 HFBR 骨形成过程中矿物质含量的替代测量； 3) 采用 FT-IR 显微光谱法确定胶原蛋白浓度范围，在该范围内，磁化转移 (MT) 效应的定量 NMR 图可用作 HFBR 中形成的骨胶原蛋白含量的替代测量； 4) 应用定量核磁共振指数来监测颅骨器官培养系统中骨形成过程中胶原蛋白和矿物质含量的变化。我们的研究如果成功，将产生定量的替代措施，可以在空间和时间上应用这些措施来监测不同骨科生物材料、生长因子、生物反应器设计和机械负载条件对体外骨形成过程的功效。我们的研究还将产生一种新颖的、非侵入性的体内成骨研究方法。