Quasi-steady-state (QUASS) reconstruction enhances T1 normalization in apparent exchange-dependent relaxation (AREX) analysis: A reevaluation of T1 correction in quantitative CEST MRI of rodent brain tumor models

Purpose: The apparent exchange-dependent relaxation (AREX) analysis has been proposed as an effective means to correct T-1 contribution in CEST quantification. However, it has been recognized that AREX T-1 correction is not straightforward if CEST scans are not performed under the equilibrium condition. Our study aimed to test if quasi-steady-state (QUASS) reconstruction could boost the accuracy of the AREX metric under common non-equilibrium scan conditions. Theory and Methods: Numerical simulation and in vivo scans were performed to assess the AREX metric accuracy. The CEST signal was simulated under different relaxation delays, RF saturation amplitudes, and durations. The AREX was evaluated as a function of the bulk water T-1 and labile proton concentration using the multiple linear regression model. AREX MRI was also assessed in brain tumor rodent models, with both apparent CEST scans and QUASS reconstruction. Results: Simulation showed that the AREX calculation from apparent CEST scans, under non-equilibrium conditions, had significant dependence on labile proton fraction ratio, RF saturation time, and T-1. In comparison, QUASS-boosted AREX depended on the labile proton fraction ratio without significant dependence on T-1 and RF saturation time. Whereas the apparent (2.7 +/- 0.8%) and QUASS MTR asymmetry (2.8 +/- 0.8%) contrast between normal and tumor regions of interest (ROIs) were significant, the difference was small. In comparison, AREX contrast between normal and tumor ROIs calculated from the apparent CEST scan and QUASS reconstruction was 3.8 +/- 1.1%/s and 4.4 +/- 1.2%/s, respectively, statistically different from each other. Conclusions: AREX analysis benefits from the QUASS-reconstructed equilibrium CEST effect for improved T-1 correction and quantitative CEST analysis.