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International audience; Objective:To explore the value of nuclear magnetic resonance (NMR) and functional assessments for follow-up of ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD).Methods:Twenty-five 53-skippable patients with DMD were included in this study; 15 were nonambulatory at baseline. All patients underwent clinical and functional assessments every 6 months using the Motor Function Measure (MFM), hand grip and key pinch strength, MoviPlate, and NMR spectroscopy and imaging studies.Results:Upper limb distal strength decreased in nonambulatory patients over the period of 1 year; ambulatory patients showed improvement during the same period. The same applied for several NMRS indices, such as phosphocreatine/adenosine triphosphate, which decreased in older patients but increased in younger ambulatory patients. Fat infiltration in the upper limbs increased linearly with age. Almost all NMR and functional assessment results correlated.Conclusions:Our results underscore complementarity of functional and NMR assessments in patients with DMD. Sensitivity to change of various indices may differ according to disease stage.

AB Purpose: At exercise onset, intramuscular oxidative energy production responds relatively slowly in comparison with the change in adenosine triphosphate demand. To determine whether the slow kinetics of oxidative adenosine triphosphate production is due to inadequate O2 supply or metabolic inertia, we studied the kinetics of intramyocellular deoxygenation (deoxy-myoglobin (Mb)) and metabolism (phosphocreatine (PCr)) using proton (1H) and phosphorus (31P) magnetic resonance spectroscopy in six healthy subjects (33 +/- 5 yr). Methods: Specifically, using dynamic plantarflexion exercise, rest to exercise and recovery were assessed at both 60% of maximum work rate (moderate intensity) and 80% of maximum work rate (heavy intensity). Results: At exercise onset, [PCr] fell without delay and with a similar time constant ([tau]) at both exercise intensities (approximately 33 s). In contrast, the increase in deoxy-Mb was delayed at exercise onset by 5-7 s, after which it increased with kinetics (moderate [tau] = 37 +/- 9 s; heavy [tau] = 29 +/- 6 s) that was not different from [tau]PCr (P > 0.05). At cessation, deoxy-Mb recovered without time delay and more rapidly ([tau] = ~20 s) than PCr ([tau] = ~33 s) (P < 0.05). Conclusions: Using a unique combination of in vivo magnetic resonance spectroscopy techniques with high time resolution, this study revealed a delay in intramuscular deoxygenation at the onset of exercise and rapid reoxygenation kinetics upon cessation. Together, these data imply that intramuscular substrate-enzyme interactions, and not O2 availability, determine the exercise onset kinetics of oxidative metabolism in healthy human skeletal muscles.

Objective To determine whether left ventricular hypertrophy can be correctly evaluated in hypertensive rats with a new nuclear magnetic resonance (NMR) imaging modality that is relatively simple to operate and provides results of constant quality while offering a high signal-to-noise ratio. DESIGN Left ventricular mass as calculated from the NMR imaging analysis was compared with the actual left ventricular mass measured by gravimetry. Methods Single-shot ultrafast spin-echo (SSFSE) imaging of hearts of Wistar-Kyoto rats and spontaneously hypertensive rats was performed at 4 T. Left ventricular mass was determined by using Simpson's rule on stacks of images acquired in systole and diastole. Results SSFSE NMR imaging performed in systole or in diastole evaluated and quantified left ventricular hypertrophy in hearts of spontaneously hypertensive rats very similarly to gravimetry. The left ventricular mass as determined by NMR was in good accordance with the actual left ventricular weight (SEE: 30.39 and 35.86 mg for the systolic and diastolic NMR acquisitions, respectively). Conclusion Using an SSFSE sequence, high-quality NMR images of the rat heart can be generated very reliably with sufficient contrast and temporal and spatial resolution, and allow precise, non-invasive and fast characterization of left ventricular hypertrophy in a hypertensive rat model.

Delayed contrast enhancement after injection of a gadolinium-chelate (Gd-chelate) is a reference imaging method to detect myocardial tissue changes. Its localization within the thickness of the myocardial wall allows differentiating various pathological processes such as myocardial infarction (MI), inflammatory myocarditis, and cardiomyopathies. The aim of the study was first to characterize benign myocarditis using quantitative delayed-enhancement imaging and then to investigate whether the measure of the extracellular volume fraction (ECV) can be used to discriminate between MI and myocarditis. In 6 patients with acute benign myocarditis (32.2 ± 13.8 year-old, subepicardial late gadolinium enhancement [LGE]) and 18 patients with MI (52.3 ± 10.9 year-old, subendocardial/transmural LGE), myocardial T1 was determined using the Modified Look-Locker Imaging (MOLLI) sequence at 3 Tesla before and after Gd-chelate injection. T1 values were compared in LGE and normal regions of the myocardium. The myocardial T1 values were normalized to the T1 of blood, and the ECV was calculated from T1 values of myocardium and blood pre- and post-Gd injection. In both myocarditis and MI, the T1 was lower in LGE regions than in normal regions of the left ventricle. T1 of LGE areas was significantly higher in myocarditis than in MI (446.8 ± 45.8 vs 360.5 ± 66.9 ms, P = 0.003) and ECV was lower in myocarditis than in MI (34.5 ± 3.3 vs 53.8 ± 13.0 %, P = 0.004). Both inflammatory process and chronic fibrosis induce LGE (subepicardial in myocarditis and subendocardial in MI). The present study demonstrates that the determination of T1 and ECV is able to differentiate the 2 histological patterns. Further investigation will indicate whether the severity of ECV changes might help refine the predictive risk of LGE in myocarditis.

Objective: To test the hypothesis that brain energy metabolism is abnormal in patients at an early stage of Huntington disease (HD). Background HD is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the HTT gene. Energy metabolism has been a major focus of HD research for many years due to several observations in both patients and models of the disease. However, there are currently no in vivo biomarkers of brain energy metabolism in HD. Design/Methods: We coupled noninvasive 31P-nuclear magnetic resonance spectroscopy (NMRS) with activation of the occipital cortex in order to measure the levels of ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) before, during and after a visual stimulus. We studied 15 HD patients at an early stage of the disease (mean motor UHDRS= 18 ±9) and 15 age- and sex-matched controls. Results: In controls, we observed an 11% increase in Pi/PCr ratio (p=0.012) and a 13% increase in Pi/ATP ratio (p=0.008) during brain activation, reflecting increased ATP synthesis and ADP levels. Subsequently, controls had a return to baseline levels during recovery (p=0.006 et 0.011 respectively). In HD patients, both Pi/PCr and Pi/ATP ratios were unchanged during and after visual stimulation, reflecting altered mitochondrial bioenergetics. In addition, in HD patients the ratio of Pi/ATP correlated with the UHDRS score during the activation (p=0.014) and recovery periods (p=0.009), while Pi/PCr ratio correlated with the UHDRS score during recovery (p=0.016), reflecting a correlation between brain energy metabolism and disease severity in HD. Conclusions: We have identified noninvasive functional biomarkers of brain energy deficit to assess therapeutic efficacy in HD. We are now extending our 31P-NMRS studies to presymptomatic individuals. Disclosure: Dr. Mochel has nothing to disclose. Dr. Nguyen has nothing to disclose. Dr. Deelchand has nothing to disclose. Dr. Rinaldi has nothing to disclose. Dr. Valabregue has nothing to disclose. Dr. Wary has nothing to disclose. Dr. Carlier has nothing to disclose. Dr. Durr has nothing to disclose. Dr. Henry has nothing to disclose.