Investigation of brain changes in ME/CFS and their assessment as potential imaging markers

Magnetic resonance imaging (MRI) scans performed in participants of the NKSG’s Hyperbaric Oxygen Therapy (HBOT) trial provide evidence of functional changes in the central nervous system in ME/CFS. These mechanisms are not yet sufficiently understood to be able to develop imaging markers. However, such markers could potentially become part of an objective ME/CFS diagnostic procedure in the future and provide important information for individualised treatment approaches. Against this background, the project aims to systematically differentiate structural and functional brain changes in ME/CFS and investigate their suitability as objective imaging markers. At the centre lies the question of whether functional changes in the central nervous system — particularly thalamocortical hyperconnectivity — can be modulated by immunoadsorption, i.e. whether functional changes observed in the brains of ME/CFS patients regress and normalise after apheresis treatment. Beyond the potential of MRI for ME/CFS biomarker development (and potential future treatment monitoring), it could provide further evidence for the rationale of immunomodulatory therapies (especially for autoantibody depletion via immunoadsorption and B-cell/plasma cell depletion).

In addition to analysing data from MRI scans, the study aims to determine whether these data correlate with immunological parameters such as individual autoantibody profiles of the trial participants. The analytical methods used include volumetric analyses, seed-based resting-state connectivity analyses, secondary analyses of thalamic connectivity and symptom burden, group stratification, and analyses of autoantibodies and thalamocortical connectivity. These will utilise imaging and biometric data collected from participants in the IA-PACS-CFS trial . IA-PACS-CFS is a phase II clinical trial investigating immunoadsorption as a treatment for ME/CFS following COVID-19 and other infections and is being conducted as part of the NKSG. The project also aims to identify possible immunological subtypes of ME/CFS, so that in the future patients can be selected in advance for appropriate treatment approaches based on the underlying disease mechanisms. In total, the analyses will include 65 ME/CFS patients and 65 age- and sex-matched healthy controls who were previously examined using an identical MRI protocol.

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