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 MTR_asym) 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 AREX_double,vdc, on tissue parameters, including T₁, T₂, semi-solid component concentration (f_m), 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 AREX_double,vdc is sensitive to amide-water exchange effects, but is relatively insensitive to T₁, T₂, f_m, nearby amine, and distant aliphatic protons, while the conventional metric MTR_asym, as well as several other APT imaging methods, are significantly affected by at least some of these confounding factors.