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 T2 , 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 T2 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.

中文翻译：

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时间依赖性扩散MRI作为Duchenne肌营养不良症小鼠模型中微结构变化的探针。

营养不良的肌肉表现出纤维大小的高度可变性和肌膜完整性的改变，通常通过组织学评估。时间依赖性扩散MRI对组织的微结构敏感，通过对营养不良和健康肌肉的年龄相关变化的研究可能有助于了解杜氏肌营养不良症（DMD）的发病和进展。我们调查了三个年龄组（7.5、22和44周）的营养不良（mdx）和野生型（WT）小鼠之间的时间依赖性扩散MRI量化年龄和与疾病相关的后肢肌肉微观结构变化的能力。确定了在六个扩散时间（Δ；范围：25-350 ms），腓肠肌和胫骨前肌的扩散时间依赖性表观扩散系数（ADC）与年龄和扩散梯度方向的关系。使用学生t检验，方差单向分析和皮尔森相关性分别比较各组和各年龄组的平均肌肉ADC，并将其与T2相关。通过组织学评估肌纤维大小和肌膜完整性，并与扩散测量结果进行比较。后肢肌肉ADC在mdx和WT动物中均表现出受限制的扩散行为，在较长的Δ处ADC值降低。在营养不良的肌肉中，ADC升高了5-15％，在较长的Δ值（≥250 ms； p <0.05，组间比较； p <0.01，年龄之间的比较）中观察到ADC的显着差异，表明扩散限制降低。T2和ADC之间没有发现显着相关性。另外，与WT动物相比，mdx中的肌纤维尺寸分布显示出更高的变异性和更低的平均纤维尺寸（p <0.001）。营养不良性肌肉显示出大量的Evans Blue Dye摄取显示出实质性的肌膜损害，这表明扩散测量结果与渗透率的变化更一致，而不是与肌肉纤维大小的变化一致。这项研究表明，当使用长Δ时，扩散MRI可以无创地区分营养不良和健康的肌肉，并具有更高的灵敏度。