Quantitative assessment of the effects of water proton concentration and water T 1 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 T 1 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, MTR asym (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 MTR asym (3.5ppm) contrast between the tumor and the contralateral brain region. Both the water content ([water proton]) and water T 1 (T 1w ) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTR asym (3.5ppm) signals and T 1w /[water proton]. Conclusion The effect of increasing T 1w 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