The exchange rate of creatine <scp>CEST</scp> in mouse brain
Ziqin Zhang, Kexin Wang, Sooyeon Park, Anna Li, Yuguo Li, Robert G. Weiss, Jiadi Xu
Abstract
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 1 ‐dependent CrCEST, and the pH response with different B 1 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 1 = 0.8 and 2 μT. The CrCEST exchange rate was found to be around 240–480 s −1 in the mouse brain, which is significantly lower than that in solutions (∼1000 s −1 ). The hypercapnia study on the mouse brain revealed that CrCEST at B 1 = 2 μT and amineCEST at B 1 = 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 1 in the brain.