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Abstract

Purpose/Introduction: Chemical exchange saturation transfer (CEST) MRI allows not only detection of low concentrated molecules, but also quantification of their exchange rates. We found out that the published quantitative description of CEST has some missing terms (1). We could identifiy these terms which allo to have accurate quatitification not only in steady-state, but also in transient state with arbitrary initial condition. This improves CEST quatitification in accuracy but also in design of speed-up experiments. Subjects and Methods: Solving the Bloch-McConnell equation (2) in eigenspace yields the follwing equations. Using the labeling efficiency alpha = w1 2 /(w1 2 +kb 2 ) the original formula for MTRasym (1) MTRasym ¼ fb kb alpha=ðR1a þfb kbÞ1eðR1aþfb kbÞtp ½1; original is extended by two additional missing appearances of alpha to MTRasym ¼ fb kb alpha=ðR1a þalpha fbkbÞ1eðR1aþalphafb kbÞtp and for the case of arbitrary initial magnetization Zi = Mi/M0 MTRasym ¼ fb kb alpha=ðR1a þ alpha fbkbÞ þ ðZi 1ÞeR1atp ðZi R1a=ðR1a þ alpha fbkbÞeðR1aþalphafb kbÞ tp½2; revised The proposed methodology was evaluated on the large-shift regime of paramagnetic CEST (paraCEST) agents using simulated Bloch-McConnell data (3) and experimental data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide (4) measured at a 7T NMR spectrometer. Results: The improved analytical QUESP/QUEST equations allow for more accurate exchange rate determination, also providing clear insights on the general principles to execute the experiments and to perform numerical evaluation. The proposed QUESP methodology was evaluated on the large-shift regime of paramagnetic CEST (paraCEST) agents using simulated data (Figure 1) and experimental data of the paramagnetic Eu(III) complex of DOTA-tetraglycineamide (Figure 2), when compared to full BM fits, the refined QUESP formulae showed improved exchange rate estimation, and this in the speed-up experiment case of only 1 s relaxation and 3 s of saturation. Discussion/Conclusion: In addition to completing the theory by missing labeling factors, we were able to accurately estimate exchange rates and extend the analytic models for the case of arbitrary initial magnetization and subsequently non-steady-state saturation. By completing the quantitative description, we could show a methodology that allows for more freedom in choosing the appropriate quantitative CEST experiments, and also to speed up the quantitative experiments without biasing the final results. This new theory needs to be spread among CEST experimentalists as quantitative evaluations in use can lead to inaccurate results.