Creatine mapping of the brain at 3T by CEST MRI

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-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 ∼23% to the GuanCEST signal at B₁ = 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 B₁ is less than 0.4 μT at 3T, when intracellular pH reduces by 0.2. Conversely, the GuanCEST decreases when B₁ 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.

Keywords: amideCEST; arginine CEST (ArgCEST); chemical exchange saturation transfer (CEST); concentration; creatine CEST (CrCEST); exchange rate; guanidino or guanidinium CEST (GuanCEST); high spectral resolution (HSR) CEST; pH mapping; polynomial Lorentzian line-shape fitting (PLOF); two-step Bloch-McConnell (BM) fitting.