title: Transfer Rate Edited experiment for the selective detection of Chemical Exchange via Saturation Transfer (TRE-CEST).
abstract: Chemical Exchange Saturation Transfer (CEST) magnetic resonance experiments have become valuable tools in magnetic resonance for the detection of low concentration solutes with far greater sensitivity than direct detection methods. Accurate measures of rates of chemical exchange provided by CEST are of particular interest to biomedical imaging communities where variations in chemical exchange can be related to subtle variations in biomarker concentration, temperature and pH within tissues using MRI. Despite their name, however, traditional CEST methods are not truly selective for chemical exchange and instead detect all forms of magnetization transfer including through-space NOE. This ambiguity crowds CEST spectra and greatly complicates subsequent data analysis. We have developed a Transfer Rate Edited CEST experiment (TRE-CEST) that uses two different types of solute labeling in order to selectively amplify signals of rapidly exchanging proton species while simultaneously suppressing 'slower' NOE-dominated magnetization transfer processes. This approach is demonstrated in the context of both NMR and MRI, where it is used to detect the labile amide protons of proteins undergoing chemical exchange (at rates⩾30s(-1)) while simultaneously eliminating signals originating from slower (∼5s(-1)) NOE-mediated magnetization transfer processes. TRE-CEST greatly expands the utility of CEST experiments in complex systems, and in-vivo, in particular, where it is expected to improve the quantification of chemical exchange and magnetization transfer rates while enabling new forms of imaging contrast.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Friedman
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Xia
authors.affiliation: Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Ravinder R
authors.initials: RR
authors.lastname: Regatte
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA.
authors.forename: Alexej
authors.initials: A
authors.lastname: Jerschow
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted
keywords: CEST; Exchange rate filter; Magnetization transfer; NOE