A novel CEST-based approach for reliably assessing skeletal muscle oxidative phosphorylation: OXCEST

Purpose To develop and validate a novel chemical exchange saturation transfer (CEST) MRI method to map skeletal muscle OXPHOS (Oxidative Phosphorylation CEST or OXCEST). Theory and Methods Our proposed OXCEST method acquires creatine (Cr)-weighted CEST maps by applying RF saturation (B 1 ) 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 (f) of B 0 . Next, the post-exercise alteration in MTR asym is hypothesized to be affected by both an exercise-induced increase in Cr and changes in B 0 inhomogeneity. By inputting post-exercise B 0 values into f, the change in MTR asym due to B 0 variation alone was estimated. Thus, the Cr-related post-exercise MTR asym could be isolated and quantified. 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 ). Results A second-order polynomial function f could reliably describe the relationship between pre-exercise MTR asym and B 0 (R 2 =0.87±0.07 in the lateral gastrocnemius (LG); R 2 =0.98±0.01 in the medial gastrocnemius (MG); R 2 =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 (R 2 >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). Conclusion OXCEST enables reliable assessment of post-exercise Cr recovery and demonstrated strong agreement with 31P-MRS.