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

PurposeTo 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. MethodsEleven U87 tumor-bearing rats were scanned at 4.7T. 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 3.5ppm, MTRasym(3.5ppm), were assessed. ResultsThe 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 T-1 (T-1w) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTRasym(3.5ppm) signals and T-1w/[water proton]. ConclusionThe 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. (c) 2016 International Society for Magnetic Resonance in Medicine