Measurement of APT using a combined CERT-AREX approach with varying duty cycles.

The goal is to develop an imaging method where contrast reflects amide-water magnetization exchange, with minimal signal contributions from other sources. Conventional chemical exchange saturation transfer (CEST) imaging of amides (often called amide proton transfer, or APT, and quantified by the metric MTRasym) is confounded by several factors unrelated to amides, such as aliphatic protons, water relaxation, and macromolecular magnetization transfer. In this work, we examined the effects of combining our previous chemical exchange rotation (CERT) approach with the non-linear AREX method while using different duty cycles (DC) for the label and reference scans. The dependencies of this approach, named AREXdouble,vdc, on tissue parameters, including T1, T2, semi-solid component concentration (fm), relayed nuclear Overhauser enhancement (rNOE), and nearby amines, were studied through numerical simulations and control sample experiments at 9.4T and 1μT irradiation. Simulations and experiments show that AREXdouble,vdc is sensitive to amide-water exchange effects, but is relatively insensitive to T1, T2, fm, nearby amine, and distant aliphatic protons, while the conventional metric MTRasym, as well as several other APT imaging methods, are significantly affected by at least some of these confounding factors.