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

PurposeTo develop and validate a novel chemical exchange saturation transfer (CEST) MRI method to map skeletal muscle OXPHOS (Oxidative Phosphorylation CEST or OXCEST). Theory and MethodsOur 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 MTRasym at 1.8 ppm). The pre-exercise MTRasym is modeled as a second-order polynomial function (f) of B0. Next, the post-exercise alteration in MTRasym 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 MTRasym due to B0 variation alone was estimated. Thus, the Cr-related post-exercise MTRasym 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 (TCr) with the ground-truth phosphocreatine recovery time constant (TPCr). ResultsA second-order polynomial function f could reliably describe the relationship between pre-exercise MTRasym 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 MTRasym was approximately 6-7% for all muscle groups. Following exercise, MTRasym increased by 11.4{+/-}4.5% in LG and 8{+/-}2.4% in MG, and showed mono-exponential recovery (R2>0.97). The combined TCr of LG and MG was found to be significantly correlated with TPCr (R{superscript 2}=0.83, p=0.005). ConclusionOXCEST enables reliable assessment of post-exercise Cr recovery and demonstrated strong agreement with 31P-MRS.