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Time-dependent diffusion MRI as a probe of microstructural changes in a mouse model of Duchenne muscular dystrophy

Lookup NU author(s): Dr Paola Porcari, Liz Greally, Professor Volker Straub, Professor Andrew Blamire

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley and Sons Ltd, 2020.

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Abstract

© 2020 John Wiley & Sons, Ltd.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.


Publication metadata

Author(s): Porcari P, Hall MG, Clark CA, Greally E, Straub V, Blamire AM

Publication type: Article

Publication status: Published

Journal: NMR in Biomedicine

Year: 2020

Volume: 33

Issue: 5

Print publication date: 01/05/2020

Online publication date: 26/02/2020

Acceptance date: 30/01/2020

Date deposited: 08/03/2021

ISSN (print): 0952-3480

ISSN (electronic): 1099-1492

Publisher: John Wiley and Sons Ltd

URL: https://doi.org/10.1002/nbm.4276

DOI: 10.1002/nbm.4276

PubMed id: 32101354


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