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，脊柱或手腕的脆弱性骨折每年影响150万美国人，是疼痛，畸形和残疾的常见原因。此外，照顾这些骨折患者的费用近100亿美元。 基于以下假设：脆弱性骨折是由低骨量引起的，世界卫生组织是根据双能X射线吸收仪（DXA）与正常的年轻成年人相比，根据双能X射线吸收仪（DXA）测量的面积骨矿物质密度确定了这些裂缝风险的风险。但是，基于真实骨矿物质密度的断裂预测已被证明既不敏感也不具体。全骨强度取决于骨组织的材料特性及其几何形状。面积的骨矿物质不测量体积骨矿物质密度，这是骨刚度和强度的主要决定因素，并且不会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。在诊断和治疗与低骨骼相关的骨骼疾病时，这种区别很重要。虽然假定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％的绝经后妇女骨折臀部且没有其他原因低骨骼。维生素D缺乏。维生素D缺乏会导致骨质乳酸，其中矿物质成分和骨骼组织的体积都降低。实际上，在骨质骨骼低骨肿块的患者中，当通过组织学评估骨骼组织时，13-33％的骨质乳核酸是骨质乳突的。正确评估骨质疏松症的潜在原因，无论是骨质疏松症还是骨质乳酸瘤，都很重要，因为这两种疾病的治疗方案是不同的，可以用双膦酸盐，PTH，钙，钙，磷酸盐，磷酸盐和维生素D补充来治疗骨质疏松症；骨质乳酸需要进行更详细的评估，因为鉴别诊断是广泛的，并且每个疾病实体都需要采取一些不同的治疗方法。由于治疗骨质疏松和骨质乳核酸的治疗是不同的，因此必须正确诊断患者的低骨骼病因。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组成和骨结构。为此，我们假设液态+固态MR成像可用于：根据骨组织矿物质组成和结构特性区分代谢骨疾病；并估计正常和病理骨骼的负载能力。这项研究的成功完成将证明使用这种非侵入性和非离子化成像技术将骨质疏松症与骨质乳酸分化，以便医生可以为风险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，这将使将液体+固态MR成像定期整合到临床扫描仪或专门的外围MRI扫描仪中，这些扫描仪可用于大规模筛查处于风险的患者。 申请人的直接职业目标是在液体和固态MR成像领域中获得专业知识，在拟议项目中产生初步结果，为知识的体系做出贡献，获得基础赠款以继续工作，并朝着科学家和首席研究员迈向独立性。 申请人将在研究过程中通过非正式的定期会议和正式会议在研究过程中封闭申请人，每两个月进行一次正式会议，以评估申请人沿项目时间表的进度。此外，申请人将接受有关MR成像的手和理论培训，以及骨生物学和病理生理学的培训。他的培训将通过参加各种研讨会，授予写作研讨会和领导力发展研讨会来增强他的培训。 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;根据研究时间表的研究进展；在指导阶段结束时提交三个手稿；根据研究工作提交基金会奖励建议；以及独立思考并计划R01级赠款提案的能力。申请人将被要求在独立阶段的第二年初设计和提交R01赠款，以确保资金连续性。 申请人的职业目标是发展为具有骨生物力学和成像专业知识的独立肌肉骨骼研究者，以实现最终的公共卫生目标，以帮助减少与骨骼病理相关的脆弱性骨折风险及其对患者和医疗保健系统的影响。虽然DXA成像是提高认识和评估处于风险中的脆弱性断裂风险的有用工具，但与这种方式相关的固有局限性以及骨骼固体和液体状态MR成像的最新进展为开发下一代诊断系统的新鲜动力提供了一种能够准确识别骨架状态变化的骨骼状态的诊断系统。