Melissa Hooijmans, researcher, dr. Hermien Kan, scientific researcher Radiology department, dr. Jedrek Burakiewicz, researcher, dr. Erik Niks, pediatric neurologist, Beatrijs Wokke, researcher/neurologist in training and prof. Jan Verschuuren, neurologist, LUMC
Progressive muscle weakness is the most noticable and limiting characteristic of Duchenne and Becker muscular dystrophies. On histology, muscle tissue in patients shows fibrosis, inflammation/edema and fatty infiltration. Currently, there are a number of new drugs being developed for treatment of DMD, however, an objective and quantitative biomarker to assess the efficacy of these drugs is lacking. The current gold standards are muscle biopsies and functional tests, however, these have disadvantages. A muscle biopsy only yields local information, is invasive and cannot be repeated often, especially in children. Functional tests rely significantly on patient cooperation and show a large variability. Therefore, a non-invasive and quantitative method to enable accurate long term assessment of treatment effects is highly needed.
Magnetic resonance imaging (MRI) can be used to assess fatty infiltration and edema/inflammation of muscular tissue with good image contrast over a large imaging plane. The technique is non-invasive, quantitative and can be applied repeatedly. Additionally, phosphorous MR spectroscopy (MRS) measurements can be applied to study changes in metabolism. In 2007, we started data acquisition of a first cross-sectional study in 16 patients with DMD, and the results have now been published. We showed that quantitative methods perform better than a visual analysis of the images, and that we can obtain a measure for muscle quality from the combination of MR imaging and strength measurements. We also performed the same measurements in patients with BMD, and showed that the T2 relaxation time – a marker for the amount of edema/inflammation in the muscle, is increased only in DMD patients and not in BMD. In addition, we showed that dystrophin levels in BMD patients do not correlate with the amount of force nor the level of fatty infiltration in the muscle, while in patients with the same mutation, these parameters correlate very well with age.
We are now in the process of acquiring longitudinal data from both BMD and DMD patients, in order to relate the differences that we observed in our cross-sectional work to disease progression.
Published articles from this research
- Wokke BH, van den Bergen JC, Hooijmans MT, Verschuuren JJ, Niks EH, Kan HE. T2 relaxation times are increased in skeletal muscle of DMD but not BMD patients. Muscle Nerve In Press.
- Hooijmans MT, Damon BM, Froeling M, Verschuuren JJ, Burakewicz J, Niks EH, Webb AG, Kan HE. Evaluation of skeletal muscle DTI in patients with Duchenne Muscular Dystrophy. NMR Biomed. 2015 Nov;28(11):1589-97.
- Wokke BH, Hooijmans MT, van den Bergen JC, Webb AG, Verschuuren JJ, Kan HE. Muscle MR spectroscopy detects elevated PDE/ATP ratios prior to fatty infiltration in Becker muscular dystrophy. NMR Biomed. 2014 Nov;27(11):1371-7
- Wokke BH, van den Bergen JC, Versluis MJ, Niks EH, Milles J, Webb AG, van Zwet EW, Aartsma-Rus A, Verschuuren JJ, Kan HE.Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy. Neuromuscul Disord. 2014 2014; May; 24(5):409-16
- van den Bergen JC, Wokke BH, Janson AA, van Duinen SG, Hulsker MH, Ginjaar HB, van Deutekom JC, Aartsma-Rus A, Kan HE, Verschuuren JJ. Dystrophin levels and clinical severity in Becker muscular dystrophy patients. J Neurol Neurosurg Psychiatry. 2014 Jul;85(7):747-53
- Wokke BH, Bos C, Reijnierse M, van Rijswijk CS, Eggers H, Webb A, Verschuuren JJ and Kan HE. Comparison of dixon and T1-weighted MR methods to assess the degree of fat infiltration in duchenne muscular dystrophy patients. J Magn Reson Imaging 2013 Sep;38(3):619-24 .