Demonstration of Accurate Multi-pool Chemical Exchange Saturation Transfer MRI Quantification - Quasi-steady-state Reconstruction Empowered Quantitative CEST Analysis

Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironment properties, yet CEST quantification has been challenging. This difficulty is because the CEST measurement depends not only on the underlying CEST system but also on the scan protocols, including RF saturation amplitude, duration, and repetition time. In addition, T normalization is not straightforward under non-equilibrium conditions. Recently, a quasi-steady-state (QUASS) algorithm was established to reconstruct the desired equilibrium state from experimental measurements. Our study aimed to determine the accuracy of spinlock-model-based multi-pool CEST quantification using numerical simulations and phantom experiments. In short, CEST Z-spectra were simulated for a representative 3-pool model, and CEST amplitudes were solved with spinlock model-based multi-pool fitting and assessed as a function of RF saturation time (Ts), repetition time (TR), and T. Although the apparent CEST signals showed significant T dependence, such relationships were not observed following QUASS reconstruction. To test the accuracy of T correction, a multi-vial phantom of nicotinamide and creatine was doped with manganese chloride, resulting in T ranging from 1 s to beyond 2 s. The multi-labile signals determined from the routine measurements showed significant dependence on Ts, TR, and T. In contrast, CEST signals from the QUASS reconstruction showed consistent quantification independent of such variables. To summarize, our study demonstrated that accurate CEST quantification is feasible in multi-pool CEST systems with the spinlock-model-based fitting of QUASS CEST MRI.