In vivo assessment of OXPHOS capacity using 3 T CrCEST MRI in Friedreich's ataxia.
Gayatri Maria Schur, Julia Dunn, Sara Nguyen, Anna Dedio, Kristin Wade, Jaclyn Tamaroff, Nithya Mitta, Neil Wilson, Ravinder Reddy, David R Lynch, Shana E McCormack
Author Information
Gayatri Maria Schur: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. gayatri.schur@nyulangone.org. ORCID
Julia Dunn: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Sara Nguyen: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Anna Dedio: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Kristin Wade: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Jaclyn Tamaroff: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Nithya Mitta: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Neil Wilson: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Ravinder Reddy: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
David R Lynch: Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Shana E McCormack: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
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.
