P.13.6 Nuclear Magnetic Resonance imaging and spectroscopy provide quantitative indices of disease severity in forearms of boys with Duchenne Muscle Dystrophy

Non-invasive measurements and quantitative evaluation of the natural course of disease need to be established in anticipation of replacement therapy in Duchenne muscular dystrophy (DMD). A cohort of 23 DMD boys (6–18years, 14 non-ambulant), were enrolled specifically to characterize disease progression of upper limbs, to be targeted in future therapeutic trials. Prior studies in the GRMD canine model showed that Nuclear Magnetic Resonance imaging (NMRI) and phosphorous spectroscopy (NMRS) could provide quantitative indices which graded with therapeutic dose. A similar approach was implemented in patients, who were examined in a 3T-60cm Siemens Magnetom TRIO system, with the arm along the body. The two arms were examined in separate sessions, to be repeated yearly, comprising NMRI (measurement of T2 of muscle water, and of fat fraction by 3-point Dixon imaging) and NMRS of phosphate metabolites. Each item lasted ∼20min. Twelve indices were analysed: –2 in NMRI: %fat signal (%F), muscle water T2 (deconvoluted from fat) –10 in NMRS: 8 ratios of metabolites combining: ATP, phosphocreatine, phospho mono- and di-esters and two pools of inorganic phosphate: cytosolic (Pia) and an anomalous alkaline pool present in dystrophic muscle (Pib), and 2 indices for respective pH values. T2 was above laboratory norms in 15% of cases, % F exceeded 10% of signal in 70% of cases and correlated to patient age ( R =.58, P R =.38 to .46, P F , ( R =.46 to .77, P Quantitative NMRI and NMRS provided a variety of indices which were abnormal in forearms of DMD patients, covering a broad range of fat infiltration, and metabolic abnormalities which graded together and with patient age and could provide biomarkers of therapeutic efficacy.