Endogenous chemical exchange saturation transfer (CEST) effects are always diluted by competing effects, such as direct water proton saturation (spillover) and semi-solid macromolecular magnetization transfer (MT). This leads to unwanted T-2 and MT signal contributions that lessen the CEST signal specificity to the underlying biochemical exchange processes. A spillover correction is of special interest for clinical static field strengths and protons resonating near the water peak. This is the case for all endogenous CEST agents, such as amide proton transfer, -OH-CEST of glycosaminoglycans, glucose or myo-inositol, and amine exchange of creatine or glutamate. All CEST effects also appear to be scaled by the T-1 relaxation time of water, as they are mediated by the water pool. This forms the motivation for simple metrics that correct the CEST signal. Based on eigenspace theory, we propose a novel magnetization transfer ratio (MTRRex), employing the inverse Z-spectrum, which eliminates spillover and semi-solid MT effects. This metric can be simply related to R-ex, the exchange-dependent relaxation rate in the rotating frame, and k(a), the inherent exchange rate. Furthermore, it can be scaled by the duty cycle, allowing for simple translation to clinical protocols. For verification, the amine proton exchange of creatine in solutions with different agar concentrations was studied experimentally at a clinical field strength of 3T, where spillover effects are large. We demonstrate that spillover can be properly corrected and that quantitative evaluation of pH and creatine concentration is possible. This proves that MTRRex is a quantitative and biophysically specific CEST-MRI metric. Applied to acute stroke induced in rat brain, the corrected CEST signal shows significantly higher contrast between the stroke area and normal tissue, as well as less B-1 dependence, than conventional approaches.
Type of Publication:
Journal article published