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Endogenous chemical exchange saturation transfer (CEST) effects are alwaysdiluted by competing effects such as direct water proton saturation (spillover)and macromolecular magnetization transfer (MT). This leads to T2-andMT-shine-through effects in the actual biochemical contrast of CEST. Therefore,a simple evaluation algorithm which corrects the CEST signal was searched for.By employing a recent eigenspace theory valid for spinlock and continuous wave(cw) CEST we predict that the inverse Z-spectrum is beneficial to Z-spectrumitself. Based on this we propose a new spillover- and MT-correctedmagnetization transfer ratio (MTRRex) yielding Rex, the exchange dependentrelaxation rate in the rotating frame. For verification, the amine protonexchange of creatine in solutions with different agar concentration was studiedexperimentally at clinical field strength of 3T. In contrast to the comparedstandard evaluation for pulsed CEST experiments, MTRasym, our approach shows noT2 or MT shine through effect. We demonstrate that spillover can be correctedproperly and also quantitative evaluation of pH and creatine concentration ispossible which proves MTRRex as quantitative CEST-MRI method. A spillovercorrection is of special interest for clinical static field strengths andprotons resonating near the water peak. This is the case for -OH-CEST effectslike gagCEST or glucoCEST, but also amine exchange of creatine or glutamatewhich require high B1. Although, only showed for amine exchange, we propose ournormalization to work generally for DIACEST, PARACEST in slow- and fastexchange regime not just as a correction, but also for quantitative CEST-MRI.Applied to acute stroke induced in rat brain, the corrected CEST signal showssignificantly higher contrast between stroke area and normal tissue as well asless B1 dependency compared to conventional approaches.

Inverse Z-spectrum analysis for MT- and spillover-corrected and  T1-compensated steady-state pulsed CEST-MRI - application to pH-weighted MRI  of acute stroke