Institute of Genetic Medicine and Centre for In Vivo Imaging, Newcastle University, Newcastle upon Tyne, UK.
Developmental Imaging and Biophysics Section, UCL GOS Institute of Child Health, London, UK.
NMR Biomed. 2020 May;33(5):e4276. doi: 10.1002/nbm.4276. Epub 2020 Feb 26.
Dystrophic muscles show a high variability of fibre sizes and altered sarcolemmal integrity, which are typically assessed by histology. Time-dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age-related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD). We investigated the capability of time-dependent diffusion MRI to quantify age and disease-related changes in hind-limb muscle microstructure between dystrophic (mdx) and wild-type (WT) mice of three age groups (7.5, 22 and 44 weeks). Diffusion time-dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion-gradient orientation at six diffusion times (Δ; range: 25-350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T , using Student's t test, one-way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements. Hind-limb muscle ADC showed characteristic restricted diffusion behaviour in both mdx and WT animals with decreasing ADC values at longer Δ. Significant differences in ADC were observed at long Δ values (≥ 250 ms; p < 0.05, comparison between groups; p < 0.01, comparison between ages) with ADC increased by 5-15% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in mdx than WT animals (p < 0.001). The extensive Evans Blue Dye uptake shown in dystrophic muscles revealed substantial sarcolemmal damage, suggesting diffusion measurements as more consistent with altered permeability rather than changes in muscle fibre sizes. This study shows the potential of diffusion MRI to non-invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long Δ.
营养不良的肌肉表现出纤维大小的高度变异性和肌膜完整性的改变，这些通常通过组织学进行评估。时变扩散 MRI 对组织微观结构敏感，通过对营养不良和健康肌肉的年龄相关性变化进行研究，有助于理解杜氏肌营养不良症 (DMD) 的发病和进展。我们研究了时变扩散 MRI 定量分析后肢肌肉微观结构的年龄和疾病相关性变化的能力，研究对象为三个年龄组（7.5、22 和 44 周）的营养不良型（mdx）和野生型（WT）小鼠。在六个扩散时间（Δ；范围：25-350ms）下，测定比目鱼肌和胫骨前肌的扩散时间相关表观扩散系数（ADCs）与年龄和扩散梯度方向的关系。使用 Student's t 检验、单向方差分析和 Pearson 相关性分析分别比较组间和组内的平均肌肉 ADC，并与 T 值进行相关性分析。通过组织学评估肌肉纤维大小和肌膜完整性，并与扩散测量结果进行比较。在 mdx 和 WT 动物中，后肢肌肉 ADC 表现出特征性的受限扩散行为，随着 Δ 的延长，ADC 值降低。在长 Δ 值（≥250ms；p＜0.05，组间比较；p＜0.01，组内比较）时，ADC 存在显著差异，且在营养不良肌肉中增加了 5-15%，表明扩散受限减少。未发现 T 值与 ADC 值之间存在显著相关性。此外，肌肉纤维大小分布在 mdx 比 WT 动物中表现出更高的变异性和更低的平均纤维大小（p＜0.001）。在营养不良的肌肉中，埃文斯蓝染料的广泛摄取表明肌膜严重受损，这表明扩散测量更符合通透性改变，而不是肌肉纤维大小的改变。本研究表明，扩散 MRI 具有潜在的非侵入性鉴别营养不良和健康肌肉的能力，在使用长 Δ 值时具有更高的敏感性。
