Quantitative assessment of the effects of water proton concentration and water T1 changes on amide proton transfer (APT) and nuclear overhauser enhancement (NOE) MRI: The origin of the APT imaging signal in brain tumor

Purpose To quantify pure chemical exchange–dependent saturation transfer (CEST) related amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signals in a rat glioma model and to investigate the mixed effects of water content and water T1 on APT and NOE imaging signals. Methods Eleven U87 tumor‐bearing rats were scanned at 4.7 T. A relatively accurate mathematical approach, based on extrapolated semisolid magnetization‐transfer reference signals, was used to remove the concurrent effects of direct water saturation and semisolid magnetization‐transfer. Pure APT and NOE signals, in addition to the commonly used magnetization‐transfer‐ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm), were assessed. Results The measured APT signal intensity of the tumor (11.06%, much larger than the value reported in the literature) was the major contributor (approximately 80.6%) to the MTRasym(3.5ppm) contrast between the tumor and the contralateral brain region. Both the water content ([water proton]) and water T1 (T1w) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTRasym(3.5ppm) signals and T1w/[water proton]. Conclusion The effect of increasing T1w on the CEST signal in the tumor was mostly eliminated by the effect of increasing water content, and the observed APT‐weighted hyperintensity in the tumor should be dominated by the increased amide proton concentration. Magn Reson Med 77:855–863, 2017. © 2016 International Society for Magnetic Resonance in Medicine