Simplified quantification of labile proton concentration-weighted chemical exchange rate (k(ws) ) with RF saturation time dependent ratiometric analysis (QUESTRA): normalization of relaxation and RF irradiation spillover effects for improved quantitative chemical exchange saturation transfer (CEST) MRI.

Chemical exchange saturation transfer MRI is an emerging imaging technique capable of detecting dilute proteins/peptides and microenvironmental properties, with promising in vivo applications. However, chemical exchange saturation transfer MRI contrast is complex, varying not only with the labile proton concentration and exchange rate, but also with experimental conditions such as field strength and radiofrequency (RF) irradiation scheme. Furthermore, the optimal RF irradiation power depends on the exchange rate, which must be estimated in order to optimize the chemical exchange saturation transfer MRI experiments. Although methods including numerical fitting with modified Bloch-McConnell equations, quantification of exchange rate with RF saturation time and power (QUEST and QUESP), have been proposed to address this relationship, they require multiple-parameter non-linear fitting and accurate relaxation measurement. Our work extended the QUEST algorithm with ratiometric analysis (QUESTRA) that normalizes the magnetization transfer ratio at labile and reference frequencies, which effectively eliminates the confounding relaxation and RF spillover effects. Specifically, the QUESTRA contrast approaches its steady state mono-exponentially at a rate determined by the reverse exchange rate (k(ws) ), with little dependence on bulk water T(1) , T(2) , RF power and chemical shift. The proposed algorithm was confirmed numerically, and validated experimentally using a tissue-like phantom of serially titrated pH compartments.