Mitochondrial Oxidative Phosphorylation Capacity in Skeletal Muscle Measured by Ultrafast Z-Spectroscopy (UFZ) MRI at 3T

Abstract Background To investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3 Tesla, utilizing ultrafast Z-spectroscopy (UFZ) MRI combined with the Polynomial and Lorentzian line-shape Fitting (PLOF) technique. Methods UFZ MRI on muscle was evaluated with turbo spin echo (TSE) and segmented 3D EPI readouts. Five healthy subjects performed in-magnet plantar flexion exercise (PFE) and subsequent changes of amide, phosphocreatine (PCr) and partial PCr mixed creatine (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 seconds for collecting high-resolution Z-spectra. Following PFE, the recovery/decay times ( τ ) 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 s and τ PCr = 98.1 ± 20.4 s versus τ CAR =36.4 ± 18.6 s and τ PCAR = 43.0 ± 13.0 s, respectively. Literature values of τ PCr obtained via 31 P MRS 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.