Proton MRI and MRSI as a Superior Methodology to Assess Oxidative Phosphorylation

Accurate determination of energy metabolism is crucial for disease indication and measurement of tissue health in disease conditions. Creatine recovery kinetics following exercise correlates to oxidative phosphorylation (OXPHOS) in tissues and can be used as a marker for understanding energy metabolism. In this study, we demonstrate that creatine chemical exchange saturation transfer (CrCEST), when combined with proton magnetic resonance spectroscopic imaging (¹H-MRSI), provides a more accurate assessment of creatine recovery kinetics in a muscle-specific manner when compared to the traditional approach, ³¹P spectroscopy.

Three male subjects were scanned on a 7T MRI scanner using either a dual-tuned 1H-31P surface coil or a ¹H 28-channel knee coil. Each scan session included baseline, in-magnet plantar flexion, and post-exercise acquisitions, with protocols tailored for mild or intense exercise.

Using ³¹P-MRS, signal from different muscle components cannot be separated in phosphocreatine dynamics (Fig 1) and the Pi peak displays broad signal changes between 4-4.8 ppm (Fig 4). In contrast, ¹H-based CrCEST and MRSI techniques provide spatially localized, muscle-specific information to detect creatine dynamics (Figs. 2, 3) and pH variations after exercise (Fig 5). Importantly, ¹H-MRSI allows confirmation that mild exercise was performed by revealing minimal pH changes (e.g., <0.1 shift), ensuring CrCEST signal detection without acidosis for assessment of mitochondrial function (Fig 6).

This combined approach enables precise, muscle-specific detection of creatine recovery kinetics. CrCEST provides accurate measurement of creatine recovery time and thus OXPHOS, while rapid ¹H-MRSI acquisition captures muscle-specific pH variations to track acidosis.

Metabolic Imaging and Spectroscopy, Chemical Exchange Saturation Transfer, Creatine, pH.