A new method was developed for fast quantitative mapping of the macromolecular proton fraction defined within the two-pool model of magnetization transfer. The method utilizes a single image with off-resonance saturation, a reference image for data normalization, and T(1), B(0), and B(1) maps with the total acquisition time ~10 min for whole-brain imaging. Macromolecular proton fraction maps are reconstructed by iterative solution of the matrix pulsed magnetization transfer equation with constrained values of other model parameters. Theoretical error model describing the variance due to noise and the bias due to deviations of constrained parameters from their actual values was formulated based on error propagation rules. The method was validated by comparison with the conventional multiparameter multipoint fit of the pulsed magnetization transfer model based on data from two healthy subjects and two multiple sclerosis patients. It was demonstrated theoretically and experimentally that accuracy of the method depends on the offset frequency and flip angle of the saturation pulse, and optimal ranges of these parameters are 4-7 kHz and 600°-900°, respectively. At optimal sampling conditions, the single-point method enables <10% relative macromolecular proton fraction errors. Comparison with the multiparameter fitting method revealed very good agreement with no significant bias and limits of agreement around ± 0.7%.
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