Assessment of Bone Composition Through a Novel Liquid/Solid State MRI Method

通过新型液态/固态 MRI 方法评估骨成分

• 批准号: 8121624
• 负责人: ARA NAZARIAN
• 金额: $ 9万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-05 至 2012-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8121624
• 关键词: Advisory Committees; Affect; Agreement; American; Anatomic Sites; Animal Experiments; Animal Model; Animals; Applications Grants; Arthroplasty; Award; Awareness; Biology; Biomechanics; Biopsy; Bone Density; Bone Diseases; Bone Mineral Contents; Bone Tissue; Cadaver; Calcified; Carbonates; Caring; Cholecalciferol; Classification; Clinical; Computer software; Controlled Environment; Data; Deformity; Developed Countries; Developing Countries; Development; Diagnosis; Differential Diagnosis; Disease; Distal; Dual-Energy X-Ray Absorptiometry; Educational workshop; Enrollment; Etiology; Evaluation; Exhibits; Failure; Fatty acid glycerol esters; Femur; Forearm; Foundations; Fracture; Functional disorder; Funding; Goals; Grant; Hand; Hand functions; Head; Head and neck structure; Health Care Costs; Healthcare Systems; Hip Fractures; Hip region structure; Histologic; Histology; Hospitals; Human; Image; Imaging Techniques; Individual; Intervention; Knowledge; Laboratories; Leadership; Liquid substance; Magnetic Resonance; Magnetic Resonance Imaging; Manuscripts; Mass Screening; Measures; Mentors; Metabolic Bone Diseases; Methods; Minerals; Modality; Modeling; Monitor; Musculoskeletal; Noise; Osteoid; Osteomalacia; Osteopenia; Osteoporosis; Outpatients; Pain; Pathologic; Pathology; Patients; Pattern; Peripheral; Phase; Physicians; Polymethyl Methacrylate; Postmenopause; Principal Investigator; Property; Proteins; Protons; Public Health; Radial; Rattus; Readiness; Relative (related person); Renal Osteodystrophy; Renal function; Reproducibility; Research; Research Personnel; Research Project Grants; Resected; Risk; Rural; Sampling; Scientist; Serum; Signal Transduction; Solid; Specimen; Spectroscopy, Fourier Transform Infrared; Structure; Supplementation; System; Techniques; Testing; Thyroid Function Tests; TimeLine; Tissues; Torque; Training; Treatment Protocols; Validation; Vertebral column; Vitamin D; Vitamin D Deficiency; Water; Woman; Work; World Health Organization; Wrist; Writing; X-Ray Computed Tomography; base; bisphosphonate; bone; bone geometry; bone mass; bone strength; calcium phosphate; career; cost; cost effective; design; disability; experience; in vivo; inorganic phosphate; mechanical behavior; meetings; mineralization; next generation; novel; novel diagnostics; physical property; prevent; skeletal; skeletal disorder; soft tissue; solid state; substantia spongiosa; tool; virtual; young adult

DESCRIPTION (provided by applicant): Fragility fractures of the hip, spine or wrist affect 1.5 million Americans annually and are a common cause of pain, deformity and disability. Moreover, caring for these fracture patients costs nearly $10 billion annually. Based on the assumption that fragility fractures are caused by low bone mass, the World Health Organization WHO) has identified individuals at risk for these fractures based on their areal bone mineral density measured by dual energy X-ray absorptiometry (DXA) compared to that of a normal young adult. However, fracture predictions based on a real bone mineral density have been shown to be neither sensitive nor specific. Whole bone strength is determined by the material properties of the bone tissue and its geometry. Areal bone mineral dnesity does not measure volumetric bone mineral density, the major determinant of bone stiffness and strength, and does not distinguish changes in bone tissue composition from changes in bone tissue volume and/or geometry. This distinction is important when diagnosing and treating skeletal diseases associated with low bone mass. While it is assumed that most fragility fractures are caused by osteoporosis, where the mineral composition of the bone tissue is normal, but the volume of bone tissue is decreased; 50% of postmenopausal women who fracture their hip and have no other cause for low bone mass, are deficient in vitamin D. Vitamin D deficiency can result in osteomalacia, where the mineral composition and bone tissue volume are both decreased. Indeed, of patients with low bone mass who fractured their hip, when their bone tissue was evaluated histologically, 13-33% was osteomalaciac. Correct assessment of the underlying causes of osteopenia, whether osteoporosis or osteomalacia, is important, as the treatment protocols for these two conditions are different, where osteoporosis may be treated with Bisphosphonates, PTH, Calcium, phosphate and vitamin D supplementation; whereas osteomalacia requires a more detailed evaluation, as the differential diagnosis is extensive, and each disease entity requires a somewhat different treatment approach. Since the treatment of osteoporosis and osteomalacia are different, it is imperative that the etiology of a patient's low bone mass be properly diagnosed. Therefore, we propose to develop a MRI based technique capable of measuring both bone tissue mineral and matrix composition and bone structure. To that end, we hypothesize that liquid+solid state MR imaging can be used to: differentiate metabolic bone diseases on the basis of bone tissue mineral composition and structural properties; and estimate the load capacity of normal and pathologic bones. Successful completion of this study will prove the feasibility of using this non-invasive and non-ionizing imaging technique to differentiate osteoporosis from osteomalacia, so that physicians may select appropriate treatment for at risk patients. This will provide an impetus to develop specialized MRI software and hardware that will make it possible to integrate liquid+solid state MR imaging routinely into clinical scanners or specialized peripheral MRI scanners that can be used for mass screening of at risk patients. The immediate career goals of the applicant are to gain expertise in the field of liquid and solid state MR imaging, generate preliminary results in the proposed project, contribute to the body of knowledge, obtain foundation grants to continue work, and move towards independence as a scientist and a principal investigator. The applicant will be supervised closed by the mentor and the co-mentor over the course of the study via informal regular meetings and formal meetings every two months to assess the applicant's progress along the project timeline. Additionally, the applicant will receive hands on and theoretical training on MR imaging, and training in bone biology and pathophysiology. His training will be augmented by attending various seminars, grant writing workshops and leadership development workshops. An advisory committee made up of experienced scientists in the field (Drs. Boskey, Bouxsein, Glimcher and Neer) will monitor the applicant's progress through meetings every six months and will be tasked with assessing the applicant's readiness to move on to the independent phase of the award, based on the applicant's fulfillment of the following criteria: independent and solid foundation in MR imaging principles, coil building and tuning, bone biology and pathophysiology; progress in research project as per study timeline; submission of three manuscripts by the end of the mentored phase; submission of a foundation award proposal based on research work; and ability to think independently and plan out a R01 level grant proposal. The applicant will be required to design and submit a R01 grant at the beginning of year two of the independent phase to assure funding continuity. The applicants' career goal is to develop as an independent musculoskeletal investigator with expertise in bone biomechanics and imaging to achieve the ultimate public health aim of helping to reduce fragility fracture risk associated with skeletal pathologies and their impact on patients and the health care system. While DXA imaging has been a useful tool to raise awareness and assess fragility fracture risks in individuals at risk, the inherent limitations associated with this modality and the recent advances in skeletal solid and liquid state MR imaging have provided a fresh impetus to develop the next generation of diagnostic systems capable of accurately identifying the underlying cause(s) of altered skeletal states.

描述（由申请人提供）：髋关节、脊柱或手腕的脆性骨折每年影响150万美国人，是疼痛、畸形和残疾的常见原因。此外，照顾这些骨折患者每年花费近100亿美元。 基于脆性骨折是由低骨量引起的假设，世界卫生组织（WHO）已经根据双能X射线吸收测定法（DXA）测量的与正常年轻人相比的区域骨矿物质密度，确定了这些骨折的风险个体。然而，基于真实的骨矿物质密度的骨折预测已被证明既不敏感也不特异。全骨强度由骨组织的材料特性及其几何形状决定。面积骨矿物质密度不测量体积骨矿物质密度，骨硬度和强度的主要决定因素，并且不区分骨组织组成的变化与骨组织体积和/或几何形状的变化。这种区别在诊断和治疗与低骨量相关的骨骼疾病时很重要。虽然人们认为大多数脆性骨折是由骨质疏松症引起的，其中骨组织的矿物质成分是正常的，但骨组织的体积减少; 50%的绝经后妇女髋部骨折并且没有其他原因导致低骨量，缺乏维生素D。维生素D缺乏可导致骨软化症，其中矿物质成分和骨组织体积都减少。事实上，在髋部骨折的低骨量患者中，当对他们的骨组织进行组织学评估时，13 - 33%是骨软化症。正确评估骨质减少的根本原因，无论是骨质疏松症还是骨软化症，都很重要，因为这两种疾病的治疗方案是不同的，其中骨质疏松症可以用双磷酸盐，PTH，钙，磷酸盐和维生素D补充剂治疗;而骨软化症需要更详细的评估，因为鉴别诊断是广泛的，每个疾病实体需要不同的治疗方法。由于骨质疏松症和骨软化症的治疗是不同的，因此必须正确诊断患者低骨量的病因。因此，我们建议开发一种基于MRI的技术，能够测量骨组织矿物质和基质成分以及骨结构。为此，我们假设，液体+固体状态的MR成像可用于：区分代谢性骨疾病的骨组织矿物成分和结构特性的基础上，并估计正常和病理骨的负荷能力。这项研究的成功完成将证明使用这种非侵入性和非电离成像技术来区分骨质疏松症和骨软化症的可行性，以便医生可以为有风险的患者选择适当的治疗方法。这将为开发专门的MRI软件和硬件提供动力，从而可以将液体+固体状态MR成像常规集成到临床扫描仪或专门的外围MRI扫描仪中，这些扫描仪可用于对风险患者进行大规模筛查。 申请人的直接职业目标是获得液体和固态MR成像领域的专业知识，在拟议项目中产生初步结果，为知识体系做出贡献，获得基金会资助以继续工作，并作为科学家和主要研究者走向独立。 在研究过程中，导师和共同导师将通过非正式定期会议和每两个月一次的正式会议对申请人进行监督，以评估申请人沿着项目时间轴的进展。此外，申请人将接受MR成像方面的实践和理论培训，以及骨生物学和病理生理学方面的培训。他的培训将通过参加各种研讨会，赠款写作讲习班和领导力发展讲习班得到加强。由该领域经验丰富的科学家组成的咨询委员会（博士. Boskey，Bouxsein，Glimcher和Neer）将通过会议每六个月监测申请人的进展，并将负责评估申请人的准备进入独立阶段的奖励，根据申请人的满足以下标准：在MR成像原理、线圈构建和调整、骨生物学和病理生理学方面有独立和坚实的基础;按照研究时间轴在研究项目中取得进展;在指导阶段结束前提交三份手稿;提交基于研究工作的基金会奖励提案;以及独立思考和规划R01级赠款提案的能力。申请人必须在独立阶段的第二年开始时设计并提交R01赠款，以确保资金的连续性。 申请人的职业目标是发展成为一名独立的肌肉骨骼研究者，拥有骨生物力学和成像方面的专业知识，以实现最终的公共卫生目标，即帮助降低与骨骼病理相关的脆性骨折风险及其对患者和医疗保健系统的影响。虽然DXA成像是一种有用的工具，以提高认识和评估脆弱性骨折的风险，在个人的风险，固有的局限性与这种方式和骨骼固体和液体状态的磁共振成像的最新进展提供了一个新的动力，开发下一代诊断系统能够准确地识别改变骨骼状态的根本原因（S）。