Proton exchange in aqueous urea solutions measured by water-exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro

Purpose: To characterize the proton exchange in aqueous urea solutions using a modified version of the WEX II filter at high magnetic field, and to assess the feasibility of performing quantitative urea CEST MRI on a 3T clinical MR system. Methods: In order to study the dependence of the exchange-rate constant k(sw) of urea as a function of pH and T, the WEX-spectra were acquired at 600 MHz from urea solutions in a pH range from 6.4 to 8.0 and a temperature range from T = 22 degrees C to 37 degrees C. The CEST experiments were performed on a 3T MRI scanner by applying a train of 50 Gaussian-shaped pulses, each 100-millisecond long with a spacing of 100 milliseconds, for saturation. Exchange rates of urea were calculated using the (extended) AREX metric. Results: The results showed that proton exchange in aqueous urea solutions is acid and base catalyzed with the rate constants: k(a) = (9.95 +/- 1.1) x 10(6) l/(mol.s) and k(b) = (6.21 +/- 0.21) x 10(6) l/(mol.s), respectively. Since the urea protons undergo a slow exchange with water protons, the CEST effect of urea can be observed efficiently at 3T. However, in neutral solutions the exchange rate of urea is minimal and cannot be estimated using the quantitative CEST approach. Conclusions: By means of the WEX-spectroscopy, the kinetic parameters of the proton exchange in urea solutions have been determined. It was also possible to estimate the exchange rates of urea in a broad range of pH values using the CEST method at a clinical scanner.