Comparing Multi-Pool Lorentzian Fitting Methods for Guanidinium CEST Quantification in the Human Brain at Clinical 3 T: A Validation Study Using MRS

This study aimed to evaluate the performance of our recently proposed double-step multi-pool Lorentzian fitting (DMPLF) method for extracting GuanCEST and other CEST signals in the human brain at clinical 3 T, using MRS as the reference standard.

A simulation experiment was conducted to compare the performance of DMPLF with single-step multi-pool Lorentzian fitting (MPLF) based on 5,000 Z-spectra generated using the Bloch-McConnell equation. CEST signals extracted using two methods, including APT, GuanCEST, rNOE(-3.5), and MT, were correlated with the proton concentrations used in the simulation. An in vivo study was conducted in 26 healthy volunteers on a clinical 3 T MRI system. GuanCEST signal extracted using two methods was correlated with MRS-measured total creatine (tCr). Regional analyses based on DMPLF-generated CEST maps were performed to evaluate tissue-specific CEST signal differences between gray matter (GM) and white matter (WM).

In simulation, CEST signals extracted by DMPLF demonstrated stronger correlations with the corresponding proton concentrations than those extracted by MPLF. In human study, DMPLF generated high-quality CEST maps, and the extracted GuanCEST signal was significantly correlated with MRS-measured tCr (r = 0.66, p < 0.001). Regional tissue analysis showed significantly higher APT and GuanCEST signals in GM than in WM, and higher rNOE(-3.5) and MT signals in WM than in GM.

The DMPLF robustly extracts multiple CEST signals, particularly the GuanCEST, which shows a strong correlation with MRS-measured tCr. These findings demonstrate its superior performance over the single-step MPLF method and highlight its potential for quantitative CEST analysis in clinical 3 T MRI.