Abstract
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-B(1) 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 ∼23% to the GuanCEST signal at B(1) = 0.8 μT, 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 μT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B(1) is greater than 0.4 μT with the same pH drop. CONCLUSIONS: CrCEST mapping is possible at 3T, which has potential for detecting intracellular pH and Cr concentration in brain.