MRI and MRS in Duchenne muscular dystrophy

Hermien E. Kan, Beatrijs H.A. Wokke, Nathalie Doorenweerd, Janneke van den Bergen, Erik Niks, Chiara Straathof, Jan J. G.M. Verschuuren, Huub H.M. Middelkoop, Jos Hendriksen, Andrew G. Webb and Mark van Buchem.


In Duchenne muscular dystrophy (DMD), a disease with a prevalence of 1 in 3500 boys, an X-linked mutation of the dystrophin gene causes absence of the dystrophin protein in the muscle cell membrane. This leads to progressive loss of muscular tissue resulting in weakness and ultimately failure of skeletal, respiratory and heart musculature. The expected lifespan of DMD boys is about 27 years. In addition, about 30% of DMD patients show cognitive impairment with an unknown etiology and prognosis. Recently, the Leiden Duchenne research group showed the first successful restoration of dystrophin expression in skeletal muscle in humans. For the further development of therapies, two advances are imperative:

  1. A non-invasive tool to capture tissue changes in skeletal muscle quantitatively. The development of new drugs for DMD patients requires accurate and repeated assessment of changes in skeletal muscle. The current gold standard, via muscle biopsies, only yields local information, is invasive and cannot be repeated often, especially in children. A non-invasive and quantitative method is imperative to enable accurate long term assessment of treatment effects.
  2. Understanding the etiology of the cognitive defects.
    If current treatment approaches succeed in restoring muscle strength and increasing lifespan, cognitive impairment will become an important factor limiting rehabilitation and social participation. An understanding of the structural, biochemical and genetic background of cognitive impairment is necessary to guide future treatment approaches.

In Becker muscular dystrophy (BMD), the same gene is affected, however, a partial functioning dystrophin protein is produced. In contrast to DMD, the disease variability in Becker patients is much greater. We will use MRI in a large collaborative study into the origins of the variability.


Using state-of-the-art MR methods at high field strengths, this project aims to:

  1. develop non-invasive markers for tissue changes in skeletal muscle
  2. acquire a detailed understanding of the biochemical, structural and genetic background of the cognitive impairment in DMD.
  3. Study the variability in disease progression in BMD


Muscle study

Muscle weakness is a prominent feature in DMD and BMDand common MR and biopsy findings include fatty infiltration and inflammation of muscular tissue. Fatty infiltration and edema/inflammation of muscular tissue are clearly visible using MRI and will be assessed quantitatively. Additionally, phosphorous MR spectroscopy (MRS) measurements will be applied to study changes in metabolism. In this project, MR scans of the leg will be acquired at 3T and correlated to measurements of muscle force.

Fat and water image of lower leg in patient with Duchenne muscular disease

Brain study

Given the function of dystrophin in the brain and the observed abnormalities in animals it is likely that structural abnormalities are present in the brain of DMD boys and underlie the cognitive impairment. Therefore, high resolution MRI studies of DMD will be performed that focus on structural changes. Additionally, proton MRS will be performed at 7T to study biochemical differences. In collaboration with Jos Hendriksen from the Kempenhaeghe institute MR results will be correlated to neuropsychological tests.


Hermien Kan, PhD
C.J. Gorter Center for High Field MRI
Department of Radiology - C3Q
Leiden University Medical Center
Albinusdreef 2
2333 ZA Leiden
The Netherlands
Phone: +31 71 5266097
Fax: +31 71 5248256