Characterization of the dystrophic muscle by 23Na NMR and 1H NMR T2 spectrum

Abstract

The aim of the thesis is to investigate the sensitivity of novel NMR outcome measures (OM) aiming to quantify pathological changes in the dystrophic muscle. Muscular dystrophy (MD) refers to a heterogeneous group of diseases with progressive muscle wasting and associated weakness characterized by variable degrees of necrosis, regeneration, ionic homeostasis disturbances, chronic inflamma-tion, and, ultimately, resulting in the replacement of muscles by fibro-fatty tissue. My focus was on the evaluation of 23Na NMR and advanced 1H transverse relaxation time (T2) techniques as early, sensitive OM. 23Na NMR measures the tightly controlled sodium concentrations and distribution in skeletal muscle tissue. This biophysical information can be used to assess ion homeostasis and cell integrity. However, 23Na NMR suffers from a low sensitivity and in vivo concentration compared to 1H. Alterations in the muscle 1H T2, commonly interpreted as an indicator of disease activity, are linked to a variety of non-specific events like oedema, inflammation, or necrosis that precede the actual muscle replacement by fat. Protocols including different 23Na NMR and 1H T2 methods were implemented to evaluate healthy and dystrophic skeletal muscle tissues of animal models and patients. This work provides evidence that 23Na NMR could offer a sensitive outcome measure able to monitor specific alteration of the dystrophic muscle at a very early stage.