A Novel CEST-Based Approach for Reliably Assessing Skeletal Muscle Oxidative Phosphorylation: OXCEST

To develop and validate a novel chemical exchange saturation transfer (CEST) MRI method to map skeletal muscle OXPHOS (Oxidative Phosphorylation CEST or OXCEST).

Our proposed OXCEST method acquires creatine (Cr)-weighted CEST maps by applying RF saturation (B₁) at only two frequency offsets: +1.8 ppm (targeting the Cr amine resonance) and -1.8 ppm (to calculate MTR_asym at 1.8 ppm). The pre-exercise MTR_asym is modeled as a second-order polynomial function of B₀ (f(B₀)). Next, the post-exercise alteration in MTR_asym is hypothesized to be affected by both an exercise-induced increase in Cr and changes in B₀ inhomogeneity. By inputting post-exercise B₀ values into f, the change in MTR_asym due to B₀ variation alone was estimated, thus allowing for the quantification of only Cr-related post-exercise MTR_asym changes. OXCEST and ³¹P-MRS were performed in seven subjects across two sessions to compare the OXCEST-derived Cr recovery time constant (T_Cr) with the ground-truth phosphocreatine recovery time constant (T_PCr) derived by ³¹P-MRS.

Function f reliably described the relationship between pre-exercise MTR_asym and B₀ (R² = 0.87 ± 0.07 in the lateral gastrocnemius (LG); R² = 0.98 ± 0.01 in the medial gastrocnemius (MG); R² = 0.96 ± 0.03 in the soleus). The mean pre-exercise MTR_asym was approximately 6%-7% for all muscle groups. Following exercise, MTR_asym increased by 11.4% ± 4.5% in LG and 8% ± 2.4% in MG, and showed mono-exponential recovery (R² > 0.97). The combined T_Cr of LG and MG was found to be significantly correlated with T_PCr (R² = 0.83, p = 0.005).

OXCEST enables reliable assessment of post-exercise Cr recovery and demonstrates significant correlation and good agreement with ³¹P-MRS.