Creatine mapping of the brain at 3T by CEST MRI

Purpose: To assess the feasibility of CEST-based creatine (Cr) mapping in brain at 3T using the guanidino (Guan) proton resonance.Methods: Wild type and knockout mice with guanidinoacetate N-methyltransferase deficiency and low Cr and phosphocreatine (PCr) concentrations in the brain were used to assign the Cr and protein-based arginine contributions to the GuanCEST signal at 2.0 ppm. To quantify the Cr proton exchange rate, two-step Bloch-McConnell fitting was used to fit the extracted CrCEST line-shape and multi-B1 Z-spectral data. The pH response of GuanCEST was simulated to demonstrate its potential for pH mapping.Results: Brain Z-spectra of wild type and guanidinoacetate N-methyltransferase deficiency mice show a clear Guan proton peak at 2.0 ppm at 3T. The CrCEST signal contributes similar to 23% to the GuanCEST signal at B-1 = 0.8 mu T, where a maximum CrCEST effect of 0.007 was detected. An exchange rate range of 200-300 s(-1) was estimated for the Cr Guan protons. As revealed by the simulation, an elevated GuanCEST in the brain is observed when B-1 is less than 0.4 mu T at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B-1 is greater than 0.4 mu T with the same pH drop.Conclusions: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.