Muscle Quality and Function
John Thornton1

1MRC Centre for Neuromuscular Diseases, University College London, London, United Kingdom

Synopsis

Target audience: This presentation is intended to inform those interested in the application of quantitative MRI to probe structure, function or pathology in skeletal muscle. Objectives: To outline the properties of skeletal muscle pertinent to quantitative MRI, the various MRI-accessible quantities that reflect muscle quality, and how MRI measurements correlate with disease severity and functional assessment

Introduction

Skeletal muscle makes up around 40% of adult human body mass and plays a vital role in health and function. It is a highly ordered structure, the fundamental units of which are three main fibre types: Type 1 fibres (mechanically slow and rely on oxidative metabolism), Type 2b/x fibre (mechanically fast and dependent upon glycolytic energy generation), and Type 2a fibres having intermediate properties (1). The distribution, density and dimensions of these myofibres, which we expect to influence water-based MRI signals, depend strongly on muscle type, age, physical training and disease status. The pathological hallmarks of neuromuscular diseases: oedema, atrophy, fat infiltration and fibrosis, are also accessible to MRI measurement. Thus quantitative MRI is an ideal tool to probe muscle quality and function in health and disease.

MRI measures relating to muscle quality

Many studies have addressed muscle-water T1, T2, magnetisation transfer, fat content and diffusion (1) properties and their dependence upon age, gender, exercise status. For example, we have shown in healthy 21.5-81y old adults a small but significant dependence of lower-limb muscle T2, fat fraction and magnetisation transfer ratio (MTR) upon age and body weight, and for MTR gender (2). There were also small inter-muscle variations, also evident in quantitative magnetisation transfer measurements (3), presumably reflecting differences in fibre-type distribution and quality. Similarly, many groups have investigated the potential of MRI to quantify muscle disease effects, which is becoming increasingly important with the growing need for effective trial outcome measures to test new therapies in muscle-wasting conditions (4). For instance, we have shown reduced MTR in denervated muscles in peripheral neuropathies (5, 6) and longitudinal changes in fat-fraction, T2 and MTR in Inclusion Body Myositis offering highly responsive potential trial end points (6).

MRI measures relating to muscle function

Both to establish tools to assess muscle physiological function, and to validate potential surrogate trial outcome measures, it is necessary to determine the relationship between MRI measures and muscle function. This has been achieved by, e.g., correlation with machine myometry, where approximately linear relationships are seen between effective muscle cross sectional area on MRI, and muscle torque (6). MRI measures have also been compared with clinical measures of function, such as ocular excursion to assess the condition of extra-ocular muscles (7), and six minute walk distance used to assess ambulation in dystrophic conditions (8); MRI may often provide a superior operator-and subject-effort independent, objective and disease-responsive surrogate functional measure.

Fat-water separation

While muscle fat content determined by Dixon-type measurements is a valuable indicator of disease severity in itself (6, 8), the presence of lipid complicates the acquisition and interpretation of data intended to probe specifically muscle water properties. A number of approaches have been proposed, particularly for obtaining fat content-independent muscle water T2 values (9, 10).

Conclusions

MRI continues to provide new measures of muscle quality and function. The increasing availability of image-acceleration methods, and more powerful gradient systems, may increase clinical application and provide even more sensitive measures of pathology, particularly of early-stage disease.

Acknowledgements

This work was funded by the UK Medical Research Council and the UCL Hospitals NIHR Biomedical Research Centre

References

1. Strijkers GJ, DROST MR, NICOLAY K. Diffusion imaging in muscle. In: Diffusion MRI: Theory, Methods, and Applications. Oxford University Press; 2011:672–689.

2. Morrow, J.M., Sinclair, C.D., Fischmann, A., Reilly, M.M., Hanna, M.G., Yousry, T.A. and Thornton, J.S., 2014. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. European Radiology, 24(7), pp.1610-1620.

3. Sinclair, C. D. J., Samson, R. S., Thomas, D. L., Weiskopf, N., Lutti, A., Thornton, J. S. and Golay, X. (2010), Quantitative magnetization transfer in in vivo healthy human skeletal muscle at 3 T. Magn Reson Med, 64: 1739–1748. doi: 10.1002/mrm.22562

4. Hollingsworth, K.G., de Sousa, P.L., Straub, V. and Carlier, P.G., 2012. Towards harmonization of protocols for MRI outcome measures in skeletal muscle studies: consensus recommendations from two TREAT-NMD NMR workshops, 2 May 2010, Stockholm, Sweden, 1–2 October 2009, Paris, France. Neuromuscular Disorders, 22, pp.S54-S67.

5. Sinclair, C.D.J., Morrow, J.M., Miranda, M.A., Davagnanam, I., Cowley, P.C., Mehta, H., Hanna, M.G., Koltzenburg, M., Yousry, T.A., Reilly, M.M. and Thornton, J.S., 2012. Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies. Journal of Neurology, Neurosurgery & Psychiatry, 83(1), pp.29-32.

6. Morrow, J.M., Sinclair, C.D., Fischmann, A., Machado, P.M., Reilly, M.M., Yousry, T.A., Thornton, J.S. and Hanna, M.G., 2016. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. The Lancet Neurology, 15(1), pp.65-77.

7. Pitceathly, R.D., Morrow, J.M., Sinclair, C.D., Woodward, C., Sweeney, M.G., Rahman, S., Plant, G.T., Ali, N., Bremner, F., Davagnanam, I. and Yousry, T.A., 2016. Extra-ocular muscle MRI in genetically-defined mitochondrial disease. European radiology, 26(1), pp.130-137.

8. Willis, T.A., Hollingsworth, K.G., Coombs, A., Sveen, M.L., Andersen, S., Stojkovic, T., Eagle, M., Mayhew, A., de Sousa, P.L., Dewar, L. and Morrow, J.M., Sinclair, C.D.J, Thornton, J.S., Bushby, K., Lochmüller, H., Hanna, M.G., Hogrel, J.Y., Carlier, P.G., Vissing, J., Straub, V. 2013. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PloS one, 8(8), p.e70993.

9. Janiczek, R.L., Gambarota, G., Sinclair, C.D., Yousry, T.A., Thornton, J.S., Golay, X. and Newbould, R.D., 2011. Simultaneous T2 and lipid quantitation using IDEAL-CPMG. Magnetic resonance in medicine, 66(5), pp.1293-1302.

10. Azzabou, N., Loureiro de Sousa, P., Caldas, E. and Carlier, P.G., 2015. Validation of a generic approach to muscle water T2 determination at 3T in fat-infiltrated skeletal muscle. Journal of Magnetic Resonance Imaging, 41(3), pp.645-653.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)