Quasi-steady-state chemical exchange saturation transfer (QUASS CEST) MRI analysis enables T₁ normalized CEST...

Chemical exchange saturation transfer (CEST) MRI depends not only on the labile proton concentration and exchange rate but also on relaxation rates, particularly T₁ relaxation time. However, T₁ normalization has shown to be not straightforward under non-steady-state conditions and in the presence of radiofrequency spillover effect. Our study aimed to test if the combined use of the new quasi-steady-state (QUASS) analysis and inverse CEST calculation facilitates T₁ normalization for improved CEST quantification. The CEST signal was simulated with Bloch-McConnell equations, and the apparent CEST, QUASS CEST, and the inverse CEST effects were calculated. T₁-normalized CEST effects were tested for their specificity to the underlying CEST system (i.e., labile proton ratio and exchange rate). CEST experiments were performed from a 9-vial phantom of independently varied concentrations of creatine (20, 40, and 60 mM) and manganese chloride (20, 30, and 40 µM) under a range of RF saturation amplitudes (0.5-4 µT) and durations (1-4 s). The simulation showed that while T₁ normalization of the apparent CEST effect was subject to noticeable T₁ contamination, the T₁-normalized inverse QUASS CEST effect had little T₁ dependence. The experimental data were analyzed using a multiple linear regression model, showing that T₁-normalized inverse QUASS analysis significantly depended on creatine concentration and saturation power (P < 0.05), not on manganese chloride concentration and saturation duration, advantageous over other CEST indices. The QUASS CEST algorithm reconstructs the steady-state CEST effect, enabling T₁-normalized inverse CEST effect calculation for improved quantification of the underlying CEST system.