In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich’s ataxia

BACKGROUND: Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by decreased expression of frataxin, a protein involved in many cellular metabolic processes, including mitochondrial oxidative phosphorylation (OXPHOS). Our objective was to assess skeletal muscle oxidative metabolism in vivo in adults with FRDA as compared to adults without FRDA using chemical exchange saturation transfer (CrCEST) MRI, which measures free creatine (Cr) over time following an in-magnet plantar flexion exercise. METHODS: Participants included adults with FRDA (n = 11) and healthy adults (n = 25). All underwent 3-Tesla CrCEST MRI of the calf before and after in-scanner plantar flexion exercise. Participants also underwent whole-body dual-energy X-ray absorptiometry (DXA) scans to measure body composition and completed questionnaires to assess physical activity. RESULTS: We found prolonged post-exercise exponential decline in CrCEST (τCr) in the lateral gastrocnemius (LG, 274 s vs. 138 s, p = 0.01) in adults with FRDA (vs. healthy adults), likely reflecting decreased OXPHOS capacity. Adults with FRDA (vs. healthy adults) also engaged different muscle groups during exercise, as indicated by muscle group-specific changes in creatine with exercise (∆CrCEST), possibly reflecting decreased coordination. Across all participants, increased adiposity and decreased usual physical activity were associated with smaller ∆CrCEST. CONCLUSION: In FRDA, CrCEST MRI may be a useful biomarker of muscle-group-specific decline in OXPHOS capacity that can be leveraged to track within-participant changes over time. Appropriate participant selection and further optimization of the exercise stimulus will enhance the utility of this technique. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10821-1.