Abstract Replacement therapy of dystrophinopathies has begun with promising results both in animals and in patients. Non-invasive quantitative tools are needed to evaluate its potential benefits or side effects but also to determine the optimal protocol. Fifteen GRMD dogs were treated by unilateral high-pressure high-volume injection into the cephalic vein with a rAAV8-U7-ESE6-ESE8 solution. They were divided into 6 groups according to the dose of viral particles and the volume injected. The lowest dose-lower volume combination was skipped. Two dogs were injected with saline only. After high dose injection, some muscles displayed up to 80% of dystrophin positive fibers. Three months after injection, we evaluated both forearms with spectroscopy at 4T and NMR imaging at 3T. Comparisons between injected and non-injected arm were blinded. All indices of mock dogs were within the reference range of the GRMD population. Both spectroscopy and imaging indices showed differences between the two arms at the highest dose irrespective of volume injected and at the intermediate dose-high volume combination. The putative identification of the treated arm proved systematically correct. Among the spectroscopy indices, Pi/PCr, PCr/ATP and PDE/(Pi + PCr) were the most sensitive and 31P NMR showed changes proportional to the number of AAV particles injected. With regard to imaging, 31 indices were evaluated in the extensor carpi radialis and flexor carpi ulnaris. The most relevant were: muscle heterogeneity in T2w images, the T1w/T2w signal ratio (SR), the T2w/PDw SR and the maximal relative signal enhancement after injection of 0.5 mmol/kg gadoteric acid. When high or intermediate doses were injected, indices actually decreased towards the normal range in both arms, with a reduction that was more substantial in the muscles of the injected side. This study demonstrated NMR ability to detect changes in dystrophic muscle structure and metabolism in response to exon-skipping therapy.