Using Amide Proton Transfer MR Imaging To Assess Glioma Response To Radiotherapy In A Rat Model

Purpose: To investigate the saturation-power dependence of amide proton transfer (APT)-weighted and nuclear Overhauser enhancement (NOE)-weighted image contrasts in a rat glioma model at4.7T and determine the optimal saturation power for APT imaging.Methods:The9L tumor-bearing rats (n=8) were scanned on a4.7-T animal magnetic resonance imaging scanner. Z-spectra over an offset range of+/-6ppm were acquired with different saturation powers, followed by the magnetization transfer-ratio asymmetry analyses around the water resonance. The three different glioma models (9L, U87, and GBM22) were used to test the obtained APT imaging protocol with the best saturation power.Results:The NOE signal upfield from the water resonance (-2.5to-5ppm) was clearly visible at lower saturation powers (0.6μT) and was larger in the contralateral normal brain tissue than in the tumor. Conversely, the APT effect downfield from the water resonance was maximized at relatively higher saturation powers (1.3to2.1μT) and was larger in the tumor than in the contralateral normal brain tissue. The NOE decreased the APT-weighted image signal, based on the magnetization transfer-ratio asymmetry analysis, but increased the APT-weighted image contrast between the tumor and contralateral normal brain tissue. The APT-weighted contrast was maximized at the saturation powers between1.3and2.1μT The APT-weighted signals were clearly observed in the three different glioma models at1.3-μT saturation power.Conclusion: The APT and NOE image signals in tumor are maximized at different saturation powers. The ideal saturation power for APT-weighted imaging is roughly1.3μT. Purpose: To assess the potential of several noninvasive functional and molecular MRI biomarkers for the assessment of glioma response to radiotherapy.Methods:Fourteen U87tumor-bearing rats were irradiated using a small-animal radiation research platform (40or20Gy), and6rats were used as controls. MRI was performed on a4.7T animal scanner, pre-radiation treatment, as well as at3,6,9, and14days post-radiation. Image features of the tumors, as well as tumor volumes and animal survival, were quantitatively compared.Results:Structural MRI showed that all irradiated tumors still grew in size during the initial days post-radiation. The apparent diffusion coefficient (ADC) values of tumors increased significantly post-radiation (40and20Gy), except at day3post-radiation, compared with pre-radiation. The tumor blood flow decreased significantly post-radiation (40and20Gy), but the relative blood flow (tumor vs. contralateral) did not show a significant change at most time points post-radiation. The amide proton transfer weighted (APTw) signals of the tumor decreased significantly at all time points post-radiation (40Gy), and also at day9post-radiation (20Gy). The blood flow and APTw maps demonstrated tumor features that were similar to those seen on gadolinium-enhanced T1-weighted images.Conclusions:Tumor ADC, blood flow, and APTw were all useful imaging biomarkers by which to predict glioma response to radiotherapy. The APTw signal was most promising for early response assessment in this model.