Quantitative MR Imaging of skeletal muscle in Duchenne and Becker muscular dystrophy

Rationale: Duchenne (DMD) and Becker (BMD) muscular dystrophy are characterized
by progressive muscle weakness. Potential therapies aim to turn the DMD
phenotype into a BMD phenotype. Outcome parameters used in current clinical
trials are muscle strength, functional tests and muscle biopsies. They carry
important disadvantages. Muscle biopsies are invasive and unattractive to apply
repeatedly, especially in children. They provide only limited information,
because only a small part of one muscle is sampled, while in DMD and BMD
various muscles are affected to different degrees. Functional tests like the 6
minute walking test have a relatively large variability and do not provide
information on muscle quality. Finally, too few patients are available for
large clinical trials testing new drugs for a subset of DMD patients with rare
mutations in the near future. Therefore, non-invasive, objective, and sensitive
methods to assess therapy efficacy are imperative.
Magnetic resonance imaging (MRI) is safe, non-invasive, provides good soft
tissue contrast over a large volume and can easily be applied repeatedly. The
technique can quantitatively assess important aspects that influence muscle
quality in DMD and BMD, namely hypertrophy or atrophy, fatty infiltration,
edema, fiber architecture and energy metabolism. Previous MRI studies have
assessed DMD patients cross-sectionally, and compared them to healthy controls.
However, as developing therapies aim to turn the severe DMD phenotype into the
less severe BMD phenotype, it is essential compare MRI readouts of DMD patients
to both BMD patients and healthy controls.

To compare quantitative muscle MRI measurements between DMD and BMD patients
and healthy controls. Comparisons will be made cross-sectionally and
longitudinally. In addition, dystrophin expression in two different leg muscles
will be studied in BMD patients.

Observational and case control study

There are no known risks associated with participating in an MRI study.
Subjects with intracranial or intraocular metal, a pacemaker, and
claustrophobia will be excluded because of potential contraindications of MRI
in such subjects. The Nederlandse Vereniging voor Kindergeneeskunde (NVK) code
of conduct *Gedragscode verzet bij minderjarigen die deelnemen aan
medisch-wetenschappelijk onderzoek* will be applied in this study.