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

Purpose 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 ‐spectra across exchange regimes. Theory and Methods The AB‐MT+n model describes continuous‐wave ‐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. Results Simulations showed that AB‐MT+n recovers the maximally accessible information from ‐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 (), whereas fast‐exchanging glucose was not captured accurately by Lorentzian, MTR, or the full analytical model under varying glutamate concentration (). In contrast, the pool‐unspecific asymmetry parameter preserved strong linearity with glucose concentration (). Reduced model orders also sufficed in seven‐pool gray matter simulations and enabled robust quantification of in vivo glucoCESL data. Conclusion AB‐MT+n provides an accurate, acquisition‐independent, modular description of continuous‐wave ‐spectra and improves quantification, particularly in the fast‐exchange regime.