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, 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 T₁ (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.