Amide proton transfer imaging with improved robustness to magnetic field inhomogeneity and magnetization transfer asymmetry using saturation with frequency alternating RF irradiation

Amide proton transfer (APT) imaging has shown promise as an indicator of tissue pH and as a marker for brain tumors. Sources of error in APT measurements include direct water saturation, and magnetization transfer (MT) from membranes and macromolecules. These are typically suppressed by postprocessing asymmetry analysis. However, this approach is strongly dependent on B₀ homogeneity and can introduce additional errors due to intrinsic MT asymmetry, aliphatic proton features opposite the amide peak and radiation damping-induced asymmetry. Although several methods exist to correct for B₀ inhomogeneity, they tremendously increase scan times and do not address errors induced by asymmetry of the z-spectrum. In this article, a novel saturation scheme-saturation with frequency alternating RF irradiation (SAFARI)-is proposed in combination with a new magnetization transfer ratio (MTR) parameter designed to generate APT images insensitive to direct water saturation and MT, even in the presence of B₀ inhomogeneity. The feasibility of the SAFARI technique is demonstrated in phantoms and in the human brain. Experimental results show that SAFARI successfully removes direct water saturation and MT contamination from APT images. It is insensitive to B₀ offsets up to 180 Hz without using additional B₀ correction, thereby dramatically reducing scanning time.