Magnetic resonance imaging and spectroscopy biomarkers for facioscapulohumeral muscular dystrophy

面肩肱型肌营养不良症的磁共振成像和光谱生物标志物

• 批准号: 9029363
• 负责人: Doris G Leung
• 金额: $ 17.89万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-15 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9029363
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Affect; Biological Markers; Childhood; Clinic; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Data; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Epigenetic Process; Facioscapulohumeral Muscular Dystrophy; Fatty acid glycerol esters; Functional disorder; Future; Genetic; Genetic Markers; Gold; Image; Imaging Techniques; Individual; Inflammation Process; Inherited; Knowledge; Literature; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Metabolic; Movement; Muscle; Muscular Dystrophies; Myopathy; Observational Study; Onset of illness; Outcome; Outcome Measure; Participant; Pathologic Processes; Patients; Performance; Phenotype; Population; Protocols documentation; Recovery; Reporting; Research; Sampling; Severity of illness; Skeletal Muscle; Staging; Symptoms; Techniques; Technology; Teenagers; Testing; Time; Validation; Walking; Weight; Work; base; cohort; disease natural history; effective therapy; epigenetic marker; imaging biomarker; insight; knowledge translation; longitudinal design; member; muscle degeneration; muscle strength; non-invasive imaging; novel; prospective; public health relevance; quantitative imaging; research study; spectroscopic imaging; tau Proteins; tool; young adult

 DESCRIPTION (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disorder that affects approximately 1 in 20,000 individuals. Although there has been progress in elucidating the mechanisms of disease in FSHD, the translation of this knowledge into effective therapies is impeded by limited information on the natural history of disease and a lack of appropriate disease biomarkers. MRI is a promising tool in the assessment of subclinical disease in skeletal muscle, and we hypothesize that it is a better predictor of changes in disease severity than the current outcome measures used in studies of muscular dystrophy. The 3 specific aims of the proposed research will use non-invasive MRI techniques to prospectively study the progression of disease in FSHD and develop imaging-based biomarkers for future clinical research. Specific Aim 1: To prospectively evaluate the radiographic progression of disease in FSHD using morphologic whole-body MRI. The prospective design of this longitudinal cohort study will allow us to test our hypothesis that whole-body T1-weighted and short-tau inversion recovery MRI sequences will detect clinical and subclinical disease progression in individual muscles over 2 years in subjects with FSHD. Specific Aim 2: To characterize early disease-related changes in normal-appearing muscle using novel metabolic imaging techniques in adolescent and young adult subjects with FSHD. We hypothesize that we will be able to detect metabolic abnormalities within muscles that appear normal on traditional MRI sequences using diffusion-weighted imaging and magnetic resonance spectroscopy. This aim is unique in its utilization of the pediatric FSHD population, which will provide valuable insight into the pathological processes that occur at the time of symptom onset. Specific Aim 3: To compare MRI-based biomarkers to clinical outcome measures in muscular dystrophy. As the most widely-used outcome measures in muscular dystrophy research are clinical outcome measures (strength and timed function tests), we will compare imaging-based biomarkers obtained using whole-body MRI to clinical outcome measures in a large cross-sectional sample of subjects with FSHD. We anticipate that MRI will prove to be a superior and more objective predictor of function in FSHD. Our proposed research will utilize a muscle-specific MRI protocol to characterize in detail longitudinal changes in the radiographic phenotype of FSHD. This information will be used to develop quantitative, non- invasive outcome measures that are needed for clinical trials and observational studies in muscle disease. We anticipate that the combination of metabolic and morphologic MRI sequences will not only become valuable disease biomarkers, but will provide a new gold standard for the validation of future genetic and epigenetic biomarkers of disease in FSHD.

 描述（由适用提供）：Facioscapolohumeral肌肉营养不良（FSHD）是一种遗传性肌肉疾病，影响了20,000名中的大约1个。尽管在阐明FSHD中疾病机制方面的进展，但对疾病自然史和缺乏适当的疾病生物标志物的信息有限，将这种知识转化为有效的疗法。 MRI是评估骨骼肌亚临床疾病的有前途的工具，我们假设它比目前在肌肉营养不良研究中使用的当前结果指标更好地预测了疾病严重程度的变化。拟议研究的3个具体目标将使用非侵入性MRI技术来前瞻性地研究FSHD中疾病的进展，并开发基于成像的生物标志物，以供未来的临床研究。具体目的1：使用形态全身MRI前瞻性评估FSHD疾病的射线照相进展。这项纵向队列研究的前瞻性设计将使我们能够检验我们的假设，即全身T1加权和短TAU反转恢复MRI序列将检测到FSHD受试者2年中单个肌肉的临床和亚临床疾病进展。具体目标2：在青少年和年轻的成年受试者中，使用新型的代谢成像技术来表征正常肌肉早期疾病相关的变化。我们假设我们将能够检测使用扩散加权成像和磁共振光谱法在传统MRI序列上看起来正常的肌肉中的代谢异常。该目标在利用小儿FSHD人群方面是独一无二的，这将为症状发作时发生的病理过程提供宝贵的见解。特定目的3：将基于MRI的生物标志物与肌肉营养不良的临床结局指标进行比较。由于肌肉营养不良研究中最广泛使用的结果度量是临床结果指标（强度和定时功能测试），我们将比较使用全身MRI获得的基于成像的生物标志物与FSHD受试者的大型横截面样本中的临床结果指标。我们预计MRI将被证明是FSHD中功能的卓越，更客观的预测指标。我们提出的研究将利用特定肌肉的MRI方案详细表征纵向变化 在FSHD的放射线型表型中。该信息将用于制定临床试验和肌肉疾病观察性研究所需的定量，非侵入性结果指标。我们预计，代谢和形态学MRI序列的结合不仅将成为有价值的疾病生物标志物，而且将为验证FSHD中疾病的未来遗传和表观遗传生物标志物提供新的黄金标准。