Characterization of microscopic environment of sodium ions in muscular dystrophies using 23Na and 1H MRI techniques

• Applicant: Teresa Gerhalter, Ph.D.
• Subject Area: Radiology ; Medical Physics, Biomedical Technology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497320374

In clinical trials for muscular dystrophies, the fat fraction, which is the degree of muscle that is replaced by fat, is currently the most employed MRI biomarker. However, an MRI biomarker preceding any macroscopic degenerative changes in muscle tissue, and that is more predictive of the evolution of DMD disease, is still lacking. Sodium (23Na) MRI has been proposed as one early and sensitive biomarker of dystrophic change.Therefore, the aim of my project is to investigate the microscopic environment of sodium ions in dystrophic muscle tissue using different MR techniques. Thus far, it has been shown that 23Na as well as special proton (1H) MRI methods offer a non-invasive way to study the progressive course of muscle diseased patients. The focus of my project is therefore to use 23Na MRI as a tool for monitoring the course of the disease and for analyzing signal changes in response to medical treatment. To this end, I plan several preclinical and clinical studies in which various MRI-based biomarkers will be examined side by side to understand the origin of MRI signal changes in dystrophic muscle tissue and to evaluate the specificity of 23Na MRI-based biomarkers.To achieve my goals, I plan to first apply different methods of 23Na and 1H MR imaging to determine the origin of 23Na signal changes in skeletal muscle tissue. In addition, potassium MRI will be employed for the first time in patients with muscular diseases to verify that the 23Na signal increases are correlated with a corresponding decrease in intracellular potassium. Second, a protocol including standard MRI sequences and advanced MRI methods will be applied in three studies with dystrophic patients, where longitudinal examinations will be performed. Finally, to analyze how 23Na MRI parameters behave in dystrophic muscle tissue during therapy, a preclinical MRI protocol using a dystrophic murine model with pharmaceutical interventions will be carried out. This should provide a sound basis for the design of an MRI protocol that enables monitoring of treatment response in future clinical studies in muscular dystrophies.

• DFG Programme: Research Grants
• International Connection: France
• Co-Investigator: Professor Armin Nagel, Ph.D.
• Cooperation Partner: Benjamin Marty, Ph.D.