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

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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.