Effective Modeling of Continuous Wave Z -Spectra for Quantitative CEST and CESL MRI Across Exchange Regimes

Chemical exchange saturation transfer (CEST) and chemical exchange-sensitive spin-lock (CESL) MRI enable spectroscopic imaging with high sensitivity, but conventional analysis methods often fail as exchange approaches the fast-exchange limit. We introduce the AB-MT+n model for robust, reproducible quantification of continuous-wave $Z$ -spectra across exchange regimes.

The AB-MT+n model describes continuous-wave $Z$ -spectra by a five-parameter basis for direct water saturation, semi-solid magnetization transfer, and fast exchange, which can be extended by off-resonant components for separable slow- and intermediate-exchanging pools. Performance was evaluated in simulations, phantoms, and in vivo glucose-enhanced CESL (glucoCESL) of a mouse brain.

Simulations showed that AB-MT+n recovers the maximally accessible information from $Z$ -spectra with minimal parameterization, with lower model orders sufficing for faster exchange. In phantoms, the slower-exchanging glutamate pool was quantified reliably by Lorentzian analysis ( $R^2>95\%$ ), whereas fast-exchanging glucose was not captured accurately by Lorentzian, MTR ${}_{\text{asym}}$ , or the full analytical model under varying glutamate concentration ( $R^2<45\%$ ). In contrast, the pool-unspecific asymmetry parameter $A$ preserved strong linearity with glucose concentration ( $R^2>80\%$ ). Reduced model orders also sufficed in seven-pool gray matter simulations and enabled robust quantification of in vivo glucoCESL data.

AB-MT+n provides an accurate, acquisition-independent, modular description of continuous-wave $Z$ -spectra and improves quantification, particularly in the fast-exchange regime.