Mitochondrial oxidative phosphorylation capacity in skeletal muscle measured by ultrafast Z-spectroscopy (UFZ) MRI at 3T

Purpose: To investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3T, utilizing ultrafast Z-spectroscopy (UFZ) combined with MRI and the Polynomial and Lorentzian line-shape Fitting (PLOF) technique. Methods: UFZ MRI on muscle was evaluated with turbo spin echo (TSE) and 3D EPI readouts. Five healthy subjects performed in-magnet plantar flexion exercise (PFE) and subsequent changes of amide, PCr, and partial PCr mixed Cr (Cr+) CEST dynamic signals post-exercise were enabled by PLOF fitting. PCr/Cr CEST signal was further refined through pH correction by using the ratios between PCr/Cr and amide signals, named PCAR/CAR, respectively. Results: UFZ MRI with TSE readout significantly reduces acquisition time, achieving a temporal resolution of <50 s for collecting high-resolution Z-spectra. Following PFE, the recovery/decay times (tau) for both PCr and Cr in the gastrocnemius muscle of the calf were notably longer when determined using PCr/Cr CEST compared to those after pH correction with amideCEST, namely tau(Cr+) = 87.1 +/- 15.8 s and tau(PCr) = 98.1 +/- 20.4 s versus tau(CAR) = 32.9 +/- 19.7 s and tau(PCAR) = 43.0 +/- 13.0 s, respectively. tau(PCr) obtained via P-31 MRS (tau(PCr) = 50.3 +/- 6.2 s) closely resemble those obtained from pH-corrected PCr/Cr CEST signals. Conclusion: The outcomes suggest potential of UFZ MRI as a robust tool for non-invasive assessment of mitochondrial function in skeletal muscles. pH correction is critical for the reliable OXPHOS measurement by CEST.