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

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 (τ_Cr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τ_Cr 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.