Physics-guided multi-dimensional scan optimization and quasi-steady-state reconstruction to enhance CEST MRI sensitivity efficiency and quantification accuracy.

Chemical exchange saturation transfer (CEST) MRI has become increasingly utilized for detecting dilute labile protons and characterizing microenvironment properties. However, the CEST MRI effect is only a few percent, and there is a need for a systematic approach to optimize scan parameters for sensitive and accurate CEST quantification. We propose multi-dimensional adjustments of key parameters such as the repetition time (TR) and RF duty cycle to optimize CEST MRI sensitivity per unit of time and utilization of quasi-steady-state (QUASS) reconstruction to recover the full CEST effect during postprocessing. Our work herein derived the CEST effect based on the generalized spin-lock CEST model and determined the interdependency of the optimal RF duty cycle and TR, showing the optimal TR decreases with the RF duty cycle but plateaus beyond 60-80 %. The accuracy of the solution was validated with both numerical simulations and CEST MRI experiments on a dual pH creatine gel phantom. The desired equilibrium CEST effect was further reconstructed with the QUASS algorithm from the optimized CEST MRI scan. In summary, our study establishes a workflow for CEST MRI scan optimization and postprocessing analysis, providing a framework to boost both the sensitivity of CEST MRI scans and the accuracy of CEST quantification. This approach holds promise for future in vivo validation and translation.