Sarah P Sherlock, Allison McCrady, Jeffrey Palmer, Haleh Aghamolaey, André Ahlgren, Per Widholm, Olof Dahlqvist Leinhard, Markus Karlsson
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This post hoc analysis evaluated participants with Dixon MRI data and corresponding functional data at baseline and weeks 49 and 97. Images were analyzed to evaluate changes in adductors, hamstrings, and quadriceps.</p><p><strong>Results: </strong>There was a positive correlation between increases in LMV and function. LMV changes in adductors (R = 0.51) and quadriceps (R = 0.54) showed a stronger correlation with function than LMV changes in hamstrings (R = 0.30). There was a negative correlation between MFF and MFI, respectively, and function in adductors (R = -0.57, R = -0.42), quadriceps (R = -0.59, R = -0.50), and hamstrings (R = -0.53, R = -048). Participants with preserved North Star Ambulatory Assessment scores had high total LMV (LMV<sub>tot</sub>) and low total MFI (MFI<sub>tot</sub>). 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引用次数: 0
摘要
简介/目的：需要改进的方法来监测杜氏肌营养不良症（DMD）的进展，特别是在临床试验的背景下。我们报告了DMD参与者的肌肉磁共振成像（MRI）参数的变化，包括瘦肌肉体积（LMV）、肌肉脂肪分数（MFF）和肌肉脂肪浸润（MFI）的变化及其与功能参数变化的关系。方法：MRI数据作为domagrozumab临床研究（NCT02310763）的一部分获得，domagrozumab是一种抗体靶向肌肉生长抑制素，可负调节骨骼肌质量。这项事后分析评估了受试者在基线和第49周和第97周的Dixon MRI数据和相应的功能数据。分析图像以评估内收肌、腘绳肌和股四头肌的变化。结果：LMV升高与功能呈正相关。内收肌LMV变化（R = 0.51）和股四头肌LMV变化（R = 0.54）与功能的相关性强于腘绳肌LMV变化（R = 0.30）。MFF和MFI分别与内收肌（R = -0.57, R = -0.42）、股四头肌（R = -0.59, R = -0.50）、腘绳肌（R = -0.53, R = -048）的功能呈负相关。保留North Star动态评估评分的参与者有较高的总LMV （LMVtot）和较低的总MFI （MFItot）。低LMVtot / MFItot比率，或低LMVtot和高MFItot的参与者，似乎有功能的快速下降和行动能力的丧失。讨论：这些发现支持使用MRI生物标志物作为DMD患者临床试验的潜在替代终点。试验注册：ClinicalTrials.gov标识符：NCT02310763。
Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy.
Introduction/aims: Improved methodologies to monitor the progression of Duchenne muscular dystrophy (DMD) are needed, especially in the context of clinical trials. We report changes in muscle magnetic resonance imaging (MRI) parameters in participants with DMD, including changes in lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) and their relationship to changes in functional parameters.
Methods: MRI data were obtained as part of a clinical study (NCT02310763) of domagrozumab, an antibody-targeting myostatin that negatively regulates skeletal muscle mass. This post hoc analysis evaluated participants with Dixon MRI data and corresponding functional data at baseline and weeks 49 and 97. Images were analyzed to evaluate changes in adductors, hamstrings, and quadriceps.
Results: There was a positive correlation between increases in LMV and function. LMV changes in adductors (R = 0.51) and quadriceps (R = 0.54) showed a stronger correlation with function than LMV changes in hamstrings (R = 0.30). There was a negative correlation between MFF and MFI, respectively, and function in adductors (R = -0.57, R = -0.42), quadriceps (R = -0.59, R = -0.50), and hamstrings (R = -0.53, R = -048). Participants with preserved North Star Ambulatory Assessment scores had high total LMV (LMVtot) and low total MFI (MFItot). Low ratios of LMVtot to MFItot, or participants with small LMVtot and high MFItot, appeared to have a rapid decline in function and loss of ambulation.
Discussion: These findings support the use of MRI biomarkers as potential surrogate endpoints in clinical trials of patients with DMD.
期刊介绍：
Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.
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