Quantitative MR Imaging markers in Neuromuscular Diseases

• Applicant: Privatdozentin Dr. Lara Schlaffke
• Subject Area: Medical Physics, Biomedical Technology ; Clinical Neurology; Neurosurgery and Neuroradiology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446281479

Worldwide incidence of inheritable muscle disease is about 1 in 2000 but diverse (> 800 variants for neuromuscular diseases) and manifest with symptoms such as muscle pain, muscle cramps, early fatigue and progressive weakness of the muscles. In severe cases, loss of ambulation, quadriplegia and a reduced life expectancy also occur. Due to microstructural changes in the muscle tissue, it is challenging to observe and quantify disease-depended changes with non-invasive methods. In the clinical routine different methods of which most of them are complimentary used to evaluate disease stage and progression. Muscle exercise testing for example is non-invasive, easily applicable, and repeatable. However, it is imprecise for subtle muscle changes and to some extent rater-dependent. Also very precise method in the clinical evaluation of muscular disease is histopathology. With this, you gain detailed information of muscle properties on a cellular level and e.g. observe the degree of sedimented glycogen. This however is invasive and mostly done in one specific region of one muscle and does not allow to compare different muscles or different properties within one muscle. Given the large variety in neuromuscular diseases, non-invasive and quantitative methods are needed, that allow for diagnosis, detailed monitoring of disease progression and evaluation of treatment strategies. Muscle imaging, with its various techniques allows on one hand for qualitative assessment and on the other hand also for quantitative assessment (qMRI). T2-mapping serves as a biomarker for inflammatory processes. It is very sensitive to even subtle changes in the muscle prior to severe oedma. mDixon is a very fast imaging technique, which allows not only the detection of fatty degeneration, but also the exact quantification of water / fat percentage. Using diffusion weighted imaging macro- and microscopic tissue state as well as inter- and intra- muscular differences can be assessed. In a previous study, we have evaluated a qMRI protocol in healthy volunteers, which is feasible for clinical usage and allows multicenter comparisons (which is of great benefit, since cohorts of rare muscular diseases are relatively small). In the proposed project, we will classify rare neuromuscular diseases (Limb-Girdle muscular dystrophy - LGMD, Inclusion Body myositis - IBM, muscular dystrophy type I - MDI, muscular dystrophy type II - MDII, glycogen storage disease type II - Pompe) as compared to the existing database of healthy volunteers. Together with the adjacent “Muskelzentrum Ruhrgebiet” we have access to a large number of patients with various disease types and will be able to recruit 10 patients for each of the above mentioned disease groups. By identifying and classifying qMRI parameters that go along with disease types and progression, we may be able to define biomarkers that allow for monitoring disease progression as well as treatment strategies in a non-invasive fashion.

• DFG Programme: Research Grants