Numerical simulation-based assessment of pH-sensitive chemical exchange saturation transfer MRI quantification...

Chemical exchange saturation transfer (CEST) MRI detects dilute labile protons via their exchange with bulk water, conferring pH sensitivity. Based on published exchange and relaxation properties, a 19-pool simulation was used to model the brain pH-dependent CEST effect and assess the accuracy of quantitative CEST (qCEST) analysis across magnetic field strengths under typical scan conditions. First, the optimal B₁ amplitude was determined by maximizing pH-sensitive amide proton transfer (APT) contrast under the equilibrium condition. Apparent and quasi-steady-state (QUASS) CEST effects were then derived under the optimal B₁ amplitude as functions of pH, RF saturation duration, relaxation delay, Ernst flip angle, and field strength. Finally, CEST effects, particularly the APT signal, were isolated with spinlock model-based Z-spectral fitting to evaluate the accuracy and consistency of CEST quantification. Our data showed that QUASS reconstruction significantly improved the consistency between simulated and equilibrium Z-spectra. The residual difference between QUASS and equilibrium CEST Z-spectra was, on average, 30 times less than that of the apparent CEST Z-spectra across field strengths, saturation, and repetition times. Also, the spinlock fitting of the QUASS CEST effect significantly reduced the residual errors 9-fold. Furthermore, the isolated APT amplitude from QUASS reconstruction was consistent and higher than the apparent CEST analysis under nonequilibrium conditions. To summarize, this study confirmed that QUASS reconstruction facilitates accurate determination of the CEST system under different scan protocols across field strengths, with the potential to help standardize CEST quantification.