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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Ryan R. Armbruster & Dushyant Kumar & Blake Benyard & Paul Jacobs & Aditi Khandavilli & Fang Liu & Ravi Prakash Reddy Nanga & Shana McCormack & Anne R. Cappola & Neil Wilson & Ravinder Reddy, 2024. "Personalized and muscle-specific OXPHOS measurement with integrated CrCEST MRI and proton MR spectroscopy," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49253-6
    DOI: 10.1038/s41467-024-49253-6
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