Burman, R.; Finkel, R. S.; Ness, K. K.; Bag, A.; Pang, Y.; Bagga, P.

Purpose: To enhance the temporal resolution of creatine (Cr)-weighted chemical exchange saturation transfer (CrCEST) MRI method to reliably assess mitochondrial OXPHOS in skeletal muscle. Methods: Our proposed Fast-CrCEST method acquires Cr maps at a temporal resolution of 10s by applying RF saturation (B1) at only +/-1.8 ppm, in contrast to the conventional CrCEST protocol, which employs six frequency offsets and requires 30s per acquisition. Given that magnetization transfer ratio asymmetry (MTRasym) depends on B0 inhomogeneity, we modeled the pre-exercise MTRasym for each muscle as a function of the corresponding B0 inhomogeneity. This model was subsequently used to correct pixel-wise post-exercise B0 shifts, allowing isolation of signal changes specifically associated with exercise-induced alterations in creatine levels. Seven subjects performed plantar flexion exercise at 3T, while CrCEST, fast-CrCEST, and 31P-MRS were performed. Recovery time constants in the gastrocnemius muscles, obtained from CrCEST (TCr) and fast-CrCEST (TfCr), were compared with those derived from 31P-MRS (TPCr). To compare the accuracy of Cr recovery time constant measurements between CrCEST and fast-CrCEST, we performed simulations using 10s and 30s sampling intervals, incorporating experimentally measured noise levels. Results: TfCr showed a significant 1:1 correlation with TPCr (R2 = 0.57, p = 0.048), whereas TCr values were approximately three times higher than TPCr, with a weaker correlation (R2=0.47, p=0.087). Conclusion: We present a novel method for correcting exercise-induced B0 shifts in fast-CrCEST. This approach enables reliable assessment of post-exercise creatine recovery, outperforming the conventional CrCEST protocol and demonstrating strong agreement with the gold-standard 31P-MRS.