Personalized and muscle-specific OXPHOS measurement with integrated CrCEST MRI and proton MR spectroscopy

Ryan R. Armbruster, Dushyant Kumar, Blake Benyard, Paul Jacobs, Aditi Khandavilli, Fang Liu, Ravi Prakash Reddy Nanga, Shana McCormack, Anne R. Cappola, Neil Wilson and Ravinder Reddy ()
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Ryan R. Armbruster: University of Pennsylvania
Dushyant Kumar: University of Pennsylvania
Blake Benyard: University of Pennsylvania
Paul Jacobs: University of Pennsylvania
Aditi Khandavilli: Cornell University
Fang Liu: University of Pennsylvania
Ravi Prakash Reddy Nanga: University of Pennsylvania
Shana McCormack: Children’s Hospital of Philadelphia
Anne R. Cappola: University of Pennsylvania
Neil Wilson: University of Pennsylvania
Ravinder Reddy: University of Pennsylvania

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Creatine chemical exchange saturation transfer (CrCEST) MRI is an emerging high resolution and noninvasive method for measuring muscle specific oxidative phosphorylation (OXPHOS). However, CrCEST measurements are sensitive to changes in muscle pH, which might confound the measurement and interpretation of creatine recovery time (τCr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τCr is expected to vary between individuals. To address this issue, a method to measure pH pre- and post-exercise and its impact on CrCEST MRI with high temporal resolution is needed. In this work, we integrate carnosine 1H- magnetic resonance spectroscopy (MRS) and 3D CrCEST to establish “mild” and “moderate/intense” exercise stimuli. We then test the dependence of CrCEST recovery time on pH using different exercise stimuli. This comprehensive metabolic imaging protocol will enable personalized, muscle specific OXPHOS measurements in both healthy aging and myriad other disease states impacting muscle mitochondria.

Date: 2024
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DOI: 10.1038/s41467-024-49253-6

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