Quantification of Hydroxyl Exchange of D‐Glucose at Physiological Conditions for Optimization of GlucoCEST MRI at 3, 7 and 9.4 Tesla
Chemical exchange saturation transfer (CEST) MRI enables the indirect detection of metabolites in small concentrations via exchange of protons in functional groups and water protons. CEST effects were observed in vivo for amide protons of proteins, amine protons of glutamate, guanidyl protons of creatine, and also for hydroxyl protons of glycosaminoglycans and myo‐inositol. As hydroxyls of sugars also showed significant CEST effects in vitro, in vivo experiments could be performed to detect the uptake of injected glucose and glucose analogs in animal models using CEST. A major problem is that optimization in vivo is complicated, especially in human subjects, as only a few protocols can be tested reliably during one examination. Moreover, exchange rates for each individual hydroxyl proton of the glucose molecule have not been determined, nor their pH dependence, thus preventing a proper and accurate simulation and investigation of saturation conditions for optimizing the attainable CEST contrast. To overcome this problem a numerical approach is followed in the present work: by quantification of glucose exchange rates at physiological conditions in vitro, a tissue‐like two‐pool model of water and a semi‐solid magnetization transfer (ssMT) can be extended by the determined glucose hydroxyl pools. This in silico pool model is then used in Bloch‐McConnell simulations to gain insight into the expected signal and contrast‐to‐noise of a glucose injection experiment as near as possible to an in vivo experiment.