Role of chemical exchange on the relayed nuclear Overhauser enhancement signal in saturation transfer MRI

Abstract

© 2021 International Society for Magnetic Resonance in MedicinePurpose: The pH sensitivity of chemical exchange-relayed nuclear Overhauser enhancement (rNOE) signal in a saturation transfer experiment is not fully understood and needs further investigation. Methods: A three-pool-exchange model was simulated assuming that the magnetization transfer between an NOE pool and water is relayed by a chemical exchange (CE) pool. The saturation transfer signals from bovine serum albumin (BSA) and egg white albumin (EWA) phantoms were measured with different pH or different D2O/H2O mixture solutions. Results: Simulation results showed that the rNOE signal is independent of the Larmor frequency of the CE pool, indicating any CE pool can effectively relay NOE magnetization. The rNOE signal is sensitive to a change of the CE pool size and/or exchange rate only if the CE becomes a rate-limiting step in the relay process. The rNOE signal from BSA phantoms showed larger pH-dependence at −3.0 ppm than those at −1.9 and −4.0 ppm. However, rNOE signals from aliphatic protons have much weaker pH-dependence than the CEST signal, suggesting that CE is unlikely the rate-limiting step and the rNOE signals in BSA are mainly relayed by fast exchanging protons. The existence of aromatic NOE was confirmed by proton spectroscopy. Conclusion: The pH-sensitivity of the rNOE signal is determined by whether the CE process is a rate-limiting step in the relay. The rNOE signal has much weaker pH-sensitivity than the CEST signal in BSA proteins, which can explain the weak pH sensitivity of rNOE in vivo.