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

Endogenous chemical exchange saturation transfer (CEST) effects are always diluted by competing effects such as direct water proton saturation (spillover) and macromolecular magnetization transfer (MT). This leads to T2-and MT-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-spectrum itself. Based on this we propose a new spillover- and MT-corrected magnetization transfer ratio (MTRRex) yielding Rex, the exchange dependent relaxation rate in the rotating frame. For verification, the amine proton exchange of creatine in solutions with different agar concentration was studied experimentally at clinical field strength of 3T. In contrast to the compared standard evaluation for pulsed CEST experiments, MTRasym, our approach shows no T2 or MT shine through effect. We demonstrate that spillover can be corrected properly and also quantitative evaluation of pH and creatine concentration is possible which proves MTRRex as quantitative CEST-MRI method. A spillover correction is of special interest for clinical static field strengths and protons resonating near the water peak. This is the case for -OH-CEST effects like gagCEST or glucoCEST, but also amine exchange of creatine or glutamate which require high B1. Although, only showed for amine exchange, we propose our normalization to work generally for DIACEST, PARACEST in slow- and fast exchange regime not just as a correction, but also for quantitative CEST-MRI. Applied to acute stroke induced in rat brain, the corrected CEST signal shows significantly higher contrast between stroke area and normal tissue as well as less B1 dependency compared to conventional approaches.