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Time\u2010dependent diffusion MRI is sensitive to tissue microstructure and its investigation through age\u2010related changes in dystrophic and healthy muscles may help the understanding of the onset and progression of Duchenne muscular dystrophy (DMD).<\/jats:p><jats:p>We investigated the capability of time\u2010dependent diffusion MRI to quantify age and disease\u2010related changes in hind\u2010limb muscle microstructure between dystrophic (<jats:italic>mdx<\/jats:italic>) and wild\u2010type (WT) mice of three age groups (7.5, 22 and 44 weeks).<\/jats:p><jats:p>Diffusion time\u2010dependent apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined versus age and diffusion\u2010gradient orientation at six diffusion times (\u0394; range: 25\u2013350 ms). Mean muscle ADCs were compared between groups and ages, and correlated with T<jats:sub>2<\/jats:sub>, using Student's t test, one\u2010way analysis of variance and Pearson correlation, respectively. Muscle fibre sizes and sarcolemmal integrity were evaluated by histology and compared with diffusion measurements.<\/jats:p><jats:p>Hind\u2010limb muscle ADC showed characteristic restricted diffusion behaviour in both <jats:italic>mdx<\/jats:italic> and WT animals with decreasing ADC values at longer \u0394. Significant differences in ADC were observed at long \u0394 values (\u2265 250 ms; <jats:italic>p<\/jats:italic> &lt; 0.05, comparison between groups; <jats:italic>p<\/jats:italic> &lt; 0.01, comparison between ages) with ADC increased by 5\u201315% in dystrophic muscles, indicative of reduced diffusion restriction. No significant correlation was found between T<jats:sub>2<\/jats:sub> and ADC. Additionally, muscle fibre size distributions showed higher variability and lower mean fibre size in <jats:italic>mdx<\/jats:italic> than WT animals (<jats:italic>p<\/jats:italic> &lt; 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.<\/jats:p><jats:p>This study shows the potential of diffusion MRI to non\u2010invasively discriminate between dystrophic and healthy muscles with enhanced sensitivity when using long \u0394.<\/jats:p>","DOI":"10.1002\/nbm.4276","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T08:44:52Z","timestamp":1582706692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Time\u2010dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular 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