Imaging of failed Regeneration in muscles of muscular dystrophy patients

该项目专注于开发和验证非侵入性生物标记物来表征疾病。 Duchenne肌营养不良症、VI型胶原相关性肌病(Ullrich和Bethlem)的研究进展 和生育不良(LGMD2B/MM)。尽管肌营养不良的预后很差，但治疗 缺乏干预措施，临床试验的结果衡量标准仅限于 肌肉功能和生活质量，肌肉破裂的血清生物标记物，以及侵入性肌肉活检。 非侵入性的、对肌肉结构变化敏感的其他量化结果指标 和成分，以促进来自临床前的有希望的新干预措施的快速翻译 从研究到临床试验。因此，项目3将重点放在磁共振成像(MRI)和 波谱(MRS)技术用于监测营养不良的病理生理学特征。在目标1中，纵向 将实施MR自然史研究，以评估下肢的进行性受累 三种不同肌营养不良人群的肌肉。此外，这一目标将评估两国关系 MR参数改变与肌力和功能丧失之间的关系。目标2是一个探索性目标 重点是开发新的MR策略来量化营养不良骨骼肌的纤维化。 最先进的序列，如超短回波和光谱成像，将被优化和测试 在Aim 2a的肌营养不良症小鼠模型中。Aim 2b将依靠开发一款新设计的 螺旋和优化脉冲序列定量标测受试者肌肉纤维化和肌内脂肪 使用临床3T系统的肌营养不良症。最后，心脏磁共振技术的组合将是 旨在评估DMD患儿的心功能和进展性心肌损害。 我们预计，本研究中优化和验证的mr技术将适用于临床。 在广泛的肌肉营养不良症中进行试验。

This project is focused on the development and validation of noninvasive biomarkers to characterize disease progression in Duchenne Muscular Dystrophy (DMD), Collagen VI related myopathies (Ullrich and Bethlem) and the Dysferiinopathies (LGMD2B/MM). Despite the poor prognosis of muscular dystrophy, therapeufic interventions have been lacking and outcome measures for clinical trials have been limited to measures of muscle funcfion and quality of life, serum biomarkers of muscle breakdown, and invasive muscle biopsies. Additional quantitative outcome measures that are noninvasive and sensitive to changes in muscle structure and composition are needed to facilitate the rapid translation of promising new interventions from preclinical studies to clinical trials. Therefore, Project 3 will focus on magnetic resonance imaging (MRI) and spectroscopy (MRS) strategies to monitor pathophysiological features of dystrophy. In Aim 1 a longitudinal MR natural history study will be implemented to evaluate the progressive involvement of the lower extremity muscles in three disfinct muscular dystrophy populations. In addifion, this aim will assess the relationship between alterafions in MR parameters and loss of muscle strength and funcfion. Aim 2 is an exploratory aim that focuses on the development of novel MR strategies to quantify fibrosis in dystrophic skeletal muscle. State-of-the art sequences, such as ultra short echo and spectroscopic imaging, will be opfimized and tested in murine models of muscular dystrophy in Aim 2a. Aim 2b will rely on the development of a newly designed coil and opfimized pulse sequences to quantitafively map muscle fibrosis and intramuscular fat in subjects with muscular dystrophy using a clinical 3T system. Finally, a combinafion of cardiac MR techniques will be implemented to evaluate cardiac funcfion and progressive myocardial involvement in boys with DMD. We anticipate that the MR techniques opfimized and validated in this study will be appropriate for clinical trials in a wide range of muscular dystrophies.