Linking exercise limitation phenotypes to muscle abnormalities in ME/CFS with MRI and NIRS

Project description

This project aims to better understand the underlying causes of exercise limitations and post-exertional malaise (PEM) in ME/CFS. In addition, research is being done on reliable and patient-oriented methods to examine muscle functioning. Recent research from Harvard University points to the existence of different types of exercise problems at the muscular level, using invasive exercise tests. This finding indicates that there may be multiple causes for exercise problems and that customised treatment is needed. In order to use these insights in practice, accurate and non-invasive measurement techniques are needed.

The project is divided into two independent sub-studies. The first sub-study is an international collaboration with a laboratory at Harvard Medical School. Central to this is the question about the relationship between different forms of exercise restriction and specific changes in the skeletal muscles. To find answers, new analysss of existing muscle samples and invasive exercise tests are utilised.

The second sub-study is an observational study in 80 ME/CFS patients with varying disease severity and 20 healthy controls. These patients come from the Dutch SNCB biobank. The second sub-study has the following objectives:

1) Validating the invasive detection method, by analysing muscle biopsies of a new ME/CFS cohort, to confirm the changes (in the first sub-study) in an independent population.

2) Testing and validating various non-invasive techniques, such as magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) for assessing muscle structure, mitochondrial function and oxygen uptake, with the aim of developing usable and reliable muscle biomarkers.

3) Investigating the relationship between exercise problems, PEM and muscle abnormalities.

Patients who participate in the sub-study are invited for four study visits. This involves: an MRI scan to look at muscle composition and a muscle biopsy, a 31P-MRS scan during short light exercise to determine muscle mitochondrial function and NIRS measurements during short light exercise to measure oxygen diffusion capacity in the muscles. And optionally a cardiopulmonary exercise test (CPET) for patients with mild and moderate symptoms; followed by questionnaires.

Results of the project should provide insights into exercise problems in ME/CFS. In addition, the research may provide non-invasive tools for conducting a diagnosis. These can be used in research, care and early diagnosis of muscle abnormalities in ME/CFS. By better understanding the causes of various exercise problems in ME/CFS, targeted treatments can be developed that match the characteristics of individual patients.

Description adapted from project website: see link above.