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: 8546512
• 负责人: ARA NAZARIAN
• 金额: $ 24.9万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546512
• 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

ABSTRACT 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 areal 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% were 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.

摘要 髋关节、脊柱或手腕的脆性骨折每年影响150万美国人，是一种常见的原因 疼痛、畸形和残疾。此外，照顾这些骨折患者每年要花费近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 (世卫组织)已经根据测量的面骨密度确定了这些骨折的风险人群 用双能X线骨密度仪(DXA)与正常青壮年进行比较。然而，骨折 基于面骨密度的预测已被证明既不敏感也不特异。整体 骨强度由骨组织的材料特性及其几何形状决定。面骨矿物质 密度不测量体积骨密度，骨密度是骨硬度和骨密度的主要决定因素 强度，并且不区分骨组织成分的变化和骨组织体积的变化 和/或几何图形。在诊断和治疗与以下相关的骨骼疾病时，这一区别非常重要 骨量低。虽然假设大多数脆性骨折是由骨质疏松症引起的，但 骨组织的矿物质成分正常，但骨组织体积减少；50% 绝经后的女性髋部骨折，没有其他原因导致骨量低，她们缺乏 维生素D缺乏会导致骨软化症，骨软化症的矿物质成分和骨组织 成交量都减少了。事实上，在髋部骨折的低骨量患者中，当他们的骨骼 组织学检查，13-33%为骨软化症。对根本原因的正确评估 无论是骨质疏松症还是骨软化症，骨量减少的情况都很重要，因为这两种疾病的治疗方案 情况不同，骨质疏松症可以用双膦酸盐、甲状旁腺素、钙、磷治疗 和维生素D补充；而骨软化症需要更详细的评估，因为 诊断是广泛的，每个疾病实体需要略有不同的治疗方法。自.以来 治疗骨质疏松症和骨软化症是不同的，必须针对患者的病因进行低 正确诊断骨量。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+固态磁共振成像可用于：根据骨骼鉴别代谢性骨病 组织矿物组成和结构特性；并估计正常和病理组织的承载能力 骨头。这项研究的成功完成将证明使用这种非侵入性和非电离技术的可行性 影像技术鉴别骨质疏松症和骨软化症，以便医生选择合适的 对高危患者的治疗。这将推动专门的MRI软件和硬件的开发 这将使将液体+固态磁共振成像常规集成到临床扫描仪或 专门的外周核磁共振扫描仪，可用于大规模筛查高危患者。 应聘者的直接职业目标是获得液态和固态磁流变仪领域的专业知识。 成像，在建议的项目中生成初步结果，有助于知识的主体，获得 基金会继续工作，并走向独立，成为一名科学家和首席研究员。 在整个学习过程中，申请者将由导师和共同导师通过 每两个月举行一次非正式定期会议和正式会议，以评估申请人在 项目时间表。此外，申请人还将接受磁共振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。他的训练将通过参加各种研讨会来加强， 资助写作工作坊和领导力发展工作坊。由以下人员组成的咨询委员会 该领域经验丰富的科学家(博斯基、布克森、格里姆彻和尼尔博士)将监督申请人的 每六个月通过会议取得进展，并将负责评估申请人是否准备好 根据申请人对下列标准的满足情况，进入裁决的独立阶段： 独立和扎实的磁共振成像原理，线圈的构建和调谐，骨生物学和 病理生理学；根据研究时间表的研究项目进展；提交三份手稿 指导阶段结束；根据研究工作提交基金会奖励建议；以及 独立思考，计划一份R01级别的拨款提案。申请者将被要求设计和 在独立阶段的第二年开始时提交R01赠款，以确保资金的连续性。 申请者的职业目标是成为一名独立的肌肉骨骼调查员，具有以下专业知识 骨生物力学和成像，以实现帮助减少脆性骨折的终极公共卫生目标 与骨骼病理相关的风险及其对患者和卫生保健系统的影响。而DXA 成像一直是提高认识和评估有风险的个人的脆性骨折风险的有用工具， 骨性固体和液态磁共振检查的固有局限性和最新进展 成像为开发下一代诊断系统提供了新的动力 准确识别骨骼状态改变的根本原因(S)。