Quantifying myofiber integrity using diffusion <scp>MRI</scp> and random permeable barrier modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice

Winters, Kerryanne Veronica; Reynaud, Olivier; Novikov, Dmitry S.; Fieremans, Els; Kim, Sungheon

doi:10.1002/mrm.27188

Cited by 21 publications

(32 citation statements)

References 79 publications

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“…The largest ADC differences were observed for diffusion times above 250 ms, which can only be achieved using stimulated echo‐based sequences . Such methods have been applied in ex‐vivo muscle studies,and more recently in animal and human muscle, but direct histological comparative data to support interpretation of diffusion imaging are sparse.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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 2 , 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 2 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.

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Section: Discussionmentioning

confidence: 99%

“…Early work applying diffusion measurements in skeletal muscle demonstrated that muscle fibres exhibit restricted diffusion behaviour . More recently, muscle structure and function have been increasingly investigated in both humans and animals using time dependence of diffusion parameters.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…A possible promising development could be using longer diffusion times with stimulated echo approaches because this allows modeling of membrane permeability and myofiber size, as recently shown in mouse models of DMD. 77,78 Current magnetic resonance perfusion MRI techniques allowing the noninvasive functional assessment of peripheral microvasculature in healthy and diseased individuals are blood oxygenation level-dependent (BOLD), arterial spin labeling (ASL), and dynamic contrast-enhanced (DCE) MRI. The functional imaging of skeletal muscle microvasculature helps in the understanding of muscular and vascular physiology and alterations of microcirculation under certain pathologic conditions such as peripheral arterial occlusive disease, diabetes mellitus, chronic compartment syndrome, and rheumatic disorders.…”

Section: P Magnetic Resonance Spectroscopymentioning

confidence: 99%

Quantitative Imaging in Muscle Diseases with Focus on Non-proton MRI and Other Advanced MRI Techniques

Weber

Nagel

Kan

et al. 2020

Semin Musculoskelet Radiol

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The role of neuromuscular imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI), especially whole-body applications, is increasingly being used for the diagnosis and monitoring of disease progression. In addition, they are considered as a powerful outcome measure in clinical trials. Because many muscle diseases have a distinct muscle involvement pattern, whole-body imaging can be of diagnostic value by identifying this pattern and thus narrowing the differential diagnosis and supporting the clinical diagnosis. In addition, more advanced MRI applications including non-proton MRI, diffusion tensor imaging, perfusion MRI, T2 mapping, and magnetic resonance spectroscopy provide deeper insights into muscle pathophysiology beyond the mere detection of fatty degeneration and/or muscle edema. In this review article, we present and discuss recent data on these quantitative MRI techniques in muscle diseases, with a particular focus on non-proton imaging techniques.

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“…32 This closely relates to permeability changes related to changes in muscle metabolism. 6 Additionally, damage found in dystrophin-deficient muscle 4,5 is thought to lead to mechanically-induced tears in the membrane, which can also be modeled as an increase in the average flux across the membrane. Bates et al 12 model permeability in this way as well, but they do not systematically examine its effect.…”

Section: Naughton and Georgiadismentioning

confidence: 99%

“…Excision and sectioning may also change the morphological features being examined. 6 Diffusion MRI (dMRI) is a promising noninvasive method that is sensitive to changes in the underlying microstructure. Much work has been done in brain matter to elucidate the relationship between the dMRI signal and the underlying microstructure.…”

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confidence: 99%

Global sensitivity analysis of skeletal muscle dMRI metrics: Effects of microstructural and pulse parameters

Naughton

Georgiadis

2019

Magnetic Resonance in Med

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Purpose: Estimating microstructural parameters of skeletal muscle from diffusion MRI (dMRI) signal requires understanding the relative importance of both microstructural and dMRI sequence parameters on the signal. This study seeks to determine the sensitivity of dMRI signal to variations in microstructural and dMRI sequence parameters, as well as assess the effect of noise on sensitivity. Methods: Using a cylindrical myocyte model of skeletal muscle, numerical solutions of the Bloch-Torrey equation were used to calculate global sensitivity indices of dMRI metrics (FA, RD, MD, λ 1 , λ 2 , λ 3) for wide ranges of microstructural and dMRI sequence parameters. The microstructural parameters were: myocyte diameter, volume fraction, membrane permeability, intra-and extracellular diffusion coefficients, and intra-and extracellular T 2 times. Two separate pulse sequences were examined, a PGSE and a generalized diffusion-weighted sequence that accommodates a larger range of diffusion times. The effect of noise and signal averaging on the sensitivity of the dMRI metrics was examined by adding synthetic noise to the simulated signal. Results: Among the examined parameters, the intracellular diffusion coefficient has the strongest effect, and myocyte diameter is more influential than permeability for FA and RD. The sensitivity indices do not vary significantly between the two pulse sequences. Also, noise strongly affects the sensitivity of the dMRI signal to microstructural variations. Conclusions: With the identification of key microstructural features that affect dMRI measurements, the reported sensitivity results can help interpret dMRI measurements of skeletal muscle in terms of the underlying microstructure and further develop parsimonious dMRI models of skeletal muscle.

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Quantifying myofiber integrity using diffusion MRI and random permeable barrier modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice

Cited by 21 publications

References 79 publications

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

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

Quantitative Imaging in Muscle Diseases with Focus on Non-proton MRI and Other Advanced MRI Techniques

Global sensitivity analysis of skeletal muscle dMRI metrics: Effects of microstructural and pulse parameters

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