Osteoarthritis: Identification of Novel Imaging Biomarkers via 23Na/1H MRI at 7 T

骨关节炎：通过 7 T 23Na/1H MRI 鉴定新型成像生物标志物

• 批准号: 8110291
• 负责人: Gregory Chang
• 金额: $ 13.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110291
• 关键词: Advisory Committees; Anatomy; Architecture; Area; Biochemical; Biological Markers; Biology; Biomechanics; Biometry; Cartilage; Clinical; Clinical Research; Clinical Sciences; Clinical Trials; Cross-Sectional Studies; Data; Defect; Degenerative polyarthritis; Deterioration; Development Plans; Diagnosis; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Environment; Epidemiology; Faculty; Feedback; Functional Imaging; Funding; Goals; Gold; Health; Hospitals; Image; Imaging Techniques; Institutes; Institution; Joints; K-Series Research Career Programs; Knee joint; Knowledge; Linear Regressions; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Monitor; Musculoskeletal Diseases; New York; New York City; Ontario; Organ; Orthopedic Surgery procedures; Orthopedics; Pathogenesis; Patient Care; Physicians; Physics; Physiologic pulse; Proteoglycan; Protons; Questionnaires; Radiology Specialty; Recruitment Activity; Reference Standards; Regression Analysis; Research; Research Design; Research Personnel; Research Project Grants; Resolution; Rheumatology; Risk; Role; Scientist; Severity of illness; Signal Transduction; Sodium; Staging; Testing; Therapeutic; Thick; Tissues; Training; Translational Research; United States National Institutes of Health; Universities; Walkers; Width; articular cartilage; bioimaging; bone; career development; clinical practice; design; disease diagnosis; drug development; image processing; imaging modality; improved; insight; joint injury; medical schools; multidisciplinary; musculoskeletal imaging; new technology; new therapeutic target; novel; patient oriented; response; responsible research conduct; retinal rods; skills; substantia spongiosa; ultra high resolution

DESCRIPTION (provided by applicant): The goal of this K23 Mentored Patient-Oriented Research Career Development Award proposal is to provide Gregory Chang, M.D., with a focused training period during which he will gain the skills to transition into an independent investigator in translational biomedical imaging research with a focus on musculoskeletal disease. The career development plan aims to strengthen Dr. Chang's skills and knowledge in three areas so that he may help bridge the gap between cutting edge imaging research and daily clinical practice. These areas include: 1) biology and clinical implications of osteoarthritis (pathogenesis, biomechanical considerations, rheumatologic and orthopedic issues in diagnosis and treatment); 2) advanced magnetic resonance imaging (MRI) techniques (MR physics, pulse sequence design, image processing), and 3) design of patient-oriented, clinical radiology studies (biostatistics, epidemiology, clinical study design, training in scientific integrity and the responsible conduct of research). This will be achieved via close mentoring by world-class faculty and via multidisciplinary coursework and seminars, which will take place across a diversity of institutions at New York University (NYU). Mentorship will be provided by Steve Abramson, M.D., Peter Walker, Ph.D., Ravinder Regatte, Ph.D., and Michael Recht, M.D., who are world- renowned for their contributions to osteoarthritis biology, biomechanics, biomarker, and imaging research. Additional key consultants James Babb, Ph.D., Christian Glaser, M.D., and Punam Saha, Ph.D., will bring expertise in biostatistics, clinical study design, osteoarthritis imaging, and image processing, respectively. Multidisciplinary coursework and seminars will take place at: 1) the NYU School of Medicine within the Departments of Biostatistics, Radiology, Rheumatology, and Orthopedic Surgery, 2) the NYU Center of Excellence on Musculoskeletal Disease, and 3) the NIH-funded Clinical and Translational Science Institute (CTSI) of NYU and the New York City Health and Hospitals Corporation (HHC). Finally, an advisory committee will provide quarterly feedback to Dr. Chang and assess his progress so that he will have the track record and preliminary data required to successfully apply for RO1 funding by the end of the career development award period. The goal of the research plan is to identify novel microstructural and biochemical imaging biomarkers of osteoarthritis (OA) via ultra high field (UHF) 7 Tesla (T) sodium and proton MRI techniques. If successful, the expected results will enhance physicians' and scientists' understanding of OA pathogenesis, and suggest a potential noninvasive means for early diagnosis and more accurate monitoring/prediction of disease progression. OA is manifested by degeneration in articular cartilage (initially decreased proteoglycan content, followed by reduced thickness) and damage to subchondral bone (microfractures, osteophytosis). However, current imaging techniques utilized to diagnose osteoarthritis (radiographs, conventional MRI at 1.5-3T) are limited in that they can only detect macroscopic structural joint damage when it is largely irreversible. The overall hypothesis of this proposal is that high resolution, 7T sodium and proton MRI will be able to detect and quantify subtle decreases in cartilage thickness, volume, and proteoglycan content and subtle alterations in subchondral trabecular bone micro-architecture (trabecular thickness, number, separation, plate-to-rod ratio, and connectivity) in subjects with varying stages of OA. The main advantage of the UHF MR scanner is the increased intrinsic signal available, which allows measurement of cartilage proteoglycan content via sodium MRI as well as high resolution imaging of cartilage and bone microstructure via proton MRI. Using this unique combined anatomic and physiologic imaging approach, we will recruit healthy, early OA (Kellgren Lawrence radiographic grade 1-2), and advanced OA (Kellgren- Lawrence grade 3-4) subjects and perform the following specific aims. In specific aim 1, we will determine whether 7T MR measures of cartilage and bone can detect disease presence and disease severity (distinguish healthy from early OA subjects, and early OA from advanced OA subjects). In specific aim 2, we will determine whether longitudinal changes in 7 T MR Measures of cartilage and bone are indicative of disease progression as assessed by reference standards (radiographs, conventional MRI, and clinical questionnaires). Finally, in specific aim 3, we will determine whether baseline values of 7T MR measures of cartilage and bone predict disease progression as assessed by reference standards (radiographs, conventional MRI, and clinical questionnaires). In summary, via multidisciplinary coursework, close mentoring by world-class faculty, and participation in a carefully-designed research project in a rich academic environment, Dr. Chang will improve upon his ability to conduct patient-oriented, clinical studies utilizing novel MRI techniques, facilitating his transition into an independent investigator in translational musculoskeletal imaging research.)

描述（由申请人提供）：这个K23指导的以患者为导向的研究职业发展奖提案的目标是提供格雷戈里张，医学博士，在此期间，他将获得技能，成为一名专注于肌肉骨骼疾病的转化生物医学成像研究的独立研究员。 职业发展计划旨在加强张博士在三个领域的技能和知识，使他可以帮助弥合尖端成像研究和日常临床实践之间的差距。这些领域包括：1）骨关节炎的生物学和临床意义（发病机理、生物力学考虑、诊断和治疗中的流变学和矫形问题）; 2）先进的磁共振成像（MRI）技术（MR物理学、脉冲序列设计、图像处理），以及3）设计以患者为导向的临床放射学研究（生物统计学、流行病学、临床研究设计、科学诚信培训和负责任的研究行为）。这将通过世界一流教师的密切指导和多学科课程和研讨会来实现，这些课程和研讨会将在纽约大学（NYU）的各种机构中进行。导师将提供史蒂夫艾布拉姆森，医学博士，彼得步行者，博士，Ravinder Regatte博士，和医学博士迈克尔·雷希特他们在骨关节炎生物学、生物力学、生物标志物和影像学研究方面的贡献享誉世界。其他关键顾问James Babb博士，Christian Glaser，医学博士，Punam Saha博士将分别带来生物统计学、临床研究设计、骨关节炎成像和图像处理方面的专业知识。多学科课程和研讨会将在以下地点举行：1）纽约大学医学院的生物统计学、放射学、流变学和整形外科系，2）纽约大学肌肉骨骼疾病卓越中心，以及3）NIH资助的纽约大学临床和转化科学研究所（CTSI）和纽约市健康与医院公司（HHC）。最后，一个咨询委员会将每季度向张博士提供反馈，并评估他的进展，以便他在职业发展奖励期结束前获得成功申请RO1资金所需的跟踪记录和初步数据。 该研究计划的目标是通过超高场（UHF）7特斯拉（T）钠和质子MRI技术识别骨关节炎（OA）的新型显微结构和生化成像生物标志物。如果成功，预期的结果将提高医生和科学家对OA发病机制的理解，并提出一种潜在的非侵入性手段，用于早期诊断和更准确的监测/预测疾病进展。OA表现为关节软骨变性（最初蛋白聚糖含量降低，随后厚度降低）和软骨下骨损伤（微骨折、骨赘病）。然而，目前用于诊断骨关节炎的成像技术（X光片，1.5 - 3T的常规MRI）是有限的，因为它们只能检测宏观结构关节损伤时，它在很大程度上是不可逆的。该提案的总体假设是，高分辨率、7T钠和质子MRI将能够检测和量化不同阶段OA受试者中软骨厚度、体积和蛋白多糖含量的细微降低以及软骨下骨小梁微结构（骨小梁厚度、数量、分离、板-棒比和连接性）的细微变化。UHF MR扫描仪的主要优点是增加了可用的内在信号，这允许通过钠MRI测量软骨蛋白聚糖含量，以及通过质子MRI对软骨和骨微观结构进行高分辨率成像。使用这种独特的结合解剖和生理成像的方法，我们将招募健康的早期OA（Kellgren Lawrence放射学1 - 2级）和晚期OA（Kellgren Lawrence 3 - 4级）受试者，并执行以下特定目标。在具体目标1中，我们将确定软骨和骨的7T MR测量是否可以检测疾病存在和疾病严重程度（区分健康与早期OA受试者，以及早期OA与晚期OA受试者）。在具体目标2中，我们将确定软骨和骨的7 T MR测量的纵向变化是否指示通过参考标准（放射照片、常规MRI和临床问卷）评估的疾病进展。最后，在具体目标3中，我们将确定软骨和骨的7T MR测量的基线值是否预测疾病进展，如通过参考标准（X线片、常规MRI和临床问卷）评估的。 总之，通过多学科的课程，由世界一流的教师密切指导，并在一个丰富的学术环境中精心设计的研究项目的参与，张博士将提高他的能力进行以患者为导向，临床研究利用新的MRI技术，促进他的过渡到一个独立的研究者在翻译肌肉骨骼成像研究。