Quantitative Assessment of Amide Proton Transfer (APT) and Nuclear Overhauser Enhancement (NOE) Imaging with Extrapolated Semi-Solid Magnetization Transfer Reference (EMR) Signals: Application to a Rat Glioma Model at 4.7 Tesla

Purpose: To quantify amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) contributions to in vivo chemical exchange saturation transfer MRI signals in tumors. Theory and Methods: Two-pool (free water and semi-solid protons) and four-pool (free water, semi-solid, amide, and upfield NOE-related protons) tissue models combined with the super-Lorentzian lineshape for semi-solid protons were used to fit wide and narrow frequency-offset magnetization-transfer (MT) data, respectively. Extrapolated semi-solid MT signals at 3.5 and 3.5 ppm from water were used as reference signals to quantify APT and NOE, respectively. Six glioma-bearing rats were scanned at 4.7 Tesla. Quantitative APT and NOE signals were compared at three saturation power levels. Results: The observed APT signals were significantly higher in the tumor (center and rim) than in the contralateral normal brain tissue at all saturation powers, and were the major contributor to the APT-weighted image contrast (based on MT asymmetry analysis) between the tumor and the normal brain tissue. The NOE (a positive confounding factor) enhanced this APT-weighted image contrast. The fitted amide pool sizes were significantly larger, while the NOE-related pool sizes were significantly smaller in the tumor than in the normal brain tissue. Conclusion: The extrapolated semi-solid magnetization transfer reference provides a relatively accurate approach for quantitatively measuring pure APT and NOE signals. (C) 2015 Wiley Periodicals, Inc.