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The effects of ageing on mouse muscle microstructure: A comparative study of time-dependent diffusion MRI and histological assessment.

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

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

The investigation of age-related changes in muscle microstructure between developmental and healthy adult mice may help in understanding the clinical features of early-onset muscle diseases, such as Duchenne muscular dystrophy.We investigated the evolution of mouse hind-limb muscle microstructure using diffusion imaging of in vivo and in vitro samples from both actively-growing and mature mice. Mean apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined as a function of diffusion time (Δ), age (7.5-, 22- and 44-week-old) and diffusion-gradient direction, applied parallel or transverse to the principal axis of the muscle fibres. We investigated a wide range of diffusion times with the goal of probing a range of diffusion lengths characteristic of muscle microstructure. We compared the diffusion time-dependent ADC of hind-limb muscles with histology.ADC was found to vary as a function of diffusion time in muscles at all stages of maturation. Muscle water diffusivity was higher in younger (7.5-week-old) than in adult mice (22- and 44-week-old mice), whereas no differences were observed between the older ages. In vitro data showed the same diffusivity pattern as in vivo data. The highlighted differences in diffusion properties between young and mature muscles suggested differences in underlying muscle microstructure, which were confirmed by histological assessment. In particular, while diffusion was more restricted in older muscle, muscle fibre size increased significantly from young to adult age. The extracellular space decreased with age by only ~1%. This suggests that the observed diffusivity differences between young and adult muscles may be due to increased membrane permeability in younger muscle associated with properties of the sarcolemma.


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: 2018

Volume: 31

Issue: 3

Print publication date: 01/03/2018

Online publication date: 09/01/2018

Acceptance date: 10/11/2017

Date deposited: 27/11/2017

ISSN (print): 0952-3480

ISSN (electronic): 1099-1492

Publisher: John Wiley & Sons Ltd.

URL: https://doi.org/10.1002/nbm.3881

DOI: 10.1002/nbm.3881


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