The exchange rate of creatine CEST in mouse brain.

Purpose: To estimate the exchange rate of creatine (Cr) CEST and to evaluate the pH sensitivity of guanidinium (Guan) CEST in the mouse brain.

Methods: Polynomial and Lorentzian line-shape fitting (PLOF) were implemented to extract the amine, amide, and Guan CEST signals from the brain Z-spectrum at 11.7T. Wild-type (WT) and knockout mice with the guanidinoacetate N-methyltransferase deficiency (GAMT ) that have low Cr and phosphocreatine (PCr) concentrations in the brain were used to extract the CrCEST signal. To quantify the CrCEST exchange rate, a two-step Bloch-McConnell (BM) fitting was used to fit the CrCEST line-shape, B -dependent CrCEST, and the pH response with different B values. The pH in the brain cells was altered by hypercapnia to measure the pH sensitivity of GuanCEST.

Results: Comparison between the Z-spectra of WT and GAMT mice suggest that the CrCEST is between 20% and 25% of the GuanCEST in the Z-spectrum at 1.95 ppm between B  = 0.8 and 2 μT. The CrCEST exchange rate was found to be around 240-480 s in the mouse brain, which is significantly lower than that in solutions (∼1000 s ). The hypercapnia study on the mouse brain revealed that CrCEST at B  = 2 μT and amineCEST at B  = 0.8 μT are highly sensitive to pH change in the WT mouse brain.

Conclusions: The in vivo CrCEST exchange rate is slow, and the acquisition parameters for the CrCEST should be adjusted accordingly. CrCEST is the major contribution to the opposite pH-dependence of GuanCEST signal under different conditions of B in the brain.