Saturation transfer (CEST and MT) MRI for characterization of U-87 MG glioma in the rat

The focus of this work was to identify the optimal magnetic resonance imaging (MRI) contrast between orthotopic U-87 MG tumours and normal appearing brain with the eventual goal of treatment response monitoring. U-87 MG human glioblastoma cells were injected into the brain of RNU nude rats (n = 9). The rats were imaged at 7 T at three timepoints for all animals: 3-5, 7-9, and 11-13 days after implantation. Whole-brain T₁-weighted (before and after gadolinium contrast agent injection), diffusion, and fluid-attenuated inversion recovery scans were performed. In addition, single-slice saturation-transfer-weighted chemical exchange saturation transfer (CEST), magnetization transfer (MT), and water saturation shift referencing (WASSR) contrast Z-spectra and T₁ and T₂ maps were also acquired. The MT and WASSR Z-spectra and T₁ map were fitted to a two-pool quantitative MT model to estimate the T₂ of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M_{0, MT}), and the magnetization exchange rate from the macromolecular pool to the free pool (R_MT). The T₁-corrected apparent exchange-dependent relaxation (AREX) metric to isolate the CEST contributions was also calculated. The lesion on M_{0, MT} and AREX maps with a B₁ of 2 μT best matched the hyperintensity on the post-contrast T₁-weighted image. There was also good separation in Z-spectra between the lesion and contralateral cortex in the 2-μT CEST and 3- and 5-μT MT Z-spectra at all time points. A pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment on MRI parameters was performed and the differences between enhancing lesion and contralateral cortex for the MT ratio with 2 μT saturation at 3.6 ppm frequency offset (corresponding to the amide chemical group) and M_{0, MT} were both strongly significant (p < 0.001) at all time points. This work has identified that differences between enhancing lesion and contralateral cortex are strongest in MTR with B₁ = 2 μT at 3.6 ppm and relative macromolecular pool size (M_{0, MT}) images over entire period of 3-13 days after cancer cell implantation.