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

Abstract

BackgroundTo 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. MethodsUFZ 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. ResultsUFZ 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 ({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 [Formula] s and{tau} PCr = 98.1 {+/-} 20.4 s versus{tau} CAR =36.4 {+/-} 18.6 s and{tau} PCAR = 43.0 {+/-} 13.0 s, respectively. Literature values of{tau} PCr obtained via 31P MRS closely resemble those obtained from pH-corrected PCr/Cr CEST signals. ConclusionThe 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.