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

Abstract

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 (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 ${\tau }_{{\mathrm{Cr}}^{+}}$ = 87.1 ± 15.8 s and ${\tau }_{\mathrm{PCr}}$ = 98.1 ± 20.4 s versus ${\tau }_{\mathrm{CAR}}$ = 32.9 ± 19.7 s and ${\tau }_{\text{PCAR}}$ = 43.0 ± 13.0 s, respectively. ${\tau }_{\mathrm{PCr}}$ obtained via ³¹P MRS (${\tau }_{\mathrm{PCr}}$ = 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.