Purpose: To understand the influence of various acquisition parameters on the ability of CEST MR-Fingerprinting (MRF) to discriminate different chemical exchange parameters and to provide tools for optimal acquisition schedule design and parameter map reconstruction. Methods: Numerical simulations were conducted using a parallel-computing implementation of the Bloch-McConnell equations, examining the effect of TR, TE, flip-angle, water T$_{1}$ and T$_{2}$, saturation-pulse duration, power, and frequency on the discrimination ability of CEST-MRF. A modified Euclidean-distance matching metric was evaluated and compared to traditional dot-product matching. L-Arginine phantoms of various concentrations and pH were scanned at 4.7T and the results compared to numerical findings. Results: Simulations for dot-product matching demonstrated that the optimal flip-angle and saturation times are 30$^{circ}$ and 1100 ms, respectively. The optimal maximal saturation power was 3.4 $mu$T for concentrated solutes with a slow exchange-rate, and 5.2 $mu$T for dilute solutes with medium-to-fast exchange-rates. Using the Euclidean-distance matching metric, much lower maximum saturation powers were required (1.6 and 2.4 $mu$T, respectively), with a slightly longer saturation time (1500 ms) and 90$^{circ}$ flip-angle. For both matching metrics, the discrimination ability increased with the repetition time. The experimental results were in agreement with simulations, demonstrating that more than a 50% reduction in scan-time can be achieved by Euclidean-distance-based matching. Conclusion: Optimization of the CEST-MRF acquisition schedule is critical for obtaining the best exchange parameter accuracy. The use of Euclidean-distance-based matching of signal trajectories simultaneously improved the discrimination ability and reduced the scan time and maximal saturation power required.
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