Development of non-invasive metabolic and microstructural MRI biomarkers in skeletal muscle

There is a growing interest in developing and applying quantitative MRI techniques in skeletal muscle affected by neuromuscular disease. Examples of such pathologies include dystrophies, amyotrophic lateral sclerosis, and metabolic diseases such as diabetes. Two MRI techniques with the potential for better understanding the structure, function, and disease of muscle are magnetization transfer (MT) [1] and diffusion [2] imaging. Both techniques have been used in brain imaging and have been shown to detect subtle changes that could not be identified from conventional anatomical images. However, in spite of the success of applying these techniques in the brain, there have been relatively few studies in the muscles [3-4], where the (extremely invasive) muscular biopsy remains the gold standard. Partly due to the limited availability of non-invasive methods of neuromuscular assessment, MRI remains an attractive alternative.
To this end, this project aims to develop reliable MT and diffusion imaging approaches to study subtle changes in muscle tissue.
Diffusion MRI has become the preferred imaging tool for visualising brain white matter anatomy, thanks to its ability to characterize the orientation of fibre bundles. Its extension to muscle, however, is challenging, due to the different properties of this tissue (namely T2 and diffusion coefficient) compared to brain parenchyma. This project aims to develop methods for applying this technique successfully to muscle, based also on the selection of the mathematical model that best characterizes diffusion in muscular fibres.
Magnetization transfer is a technique that characterizes the properties of water molecules attached to protein and lipids. Recent work suggests that this technique is sensitive to changes in the pH of tissue, and could therefore provide metabolic information [5]. This hypothesis will be tested by studying healthy calf muscle at rest and after exercise. In order to obtain reliable data, different approaches for measuring magnetization transfer data in muscle will be compared, and optimised for the specific application.
Once validated, these quantitative MR techniques will be used to extract information from healthy tissue in different conditions (before and after exercise) that can be used to understand the changes muscular tissues undergo during sport training. Additionally, the usefulness of these techniques in the assessment of patients with myopathies and with denervation secondary to amyotrophic lateral sclerosis will be tested.