Regions of interest (ROI) selection for spectral analysis and MTR_asym quantification.

<p>Left occipital glioblastoma of a 79 year old patient, CE-T1 (A) and T2-weighted images (B) with color coded ROIs: CE-T1 tumor, isolated CEST HIR within CE-T1 margins, tumor necrosis, PTCH within T2 edema margins, CSF and CLNAWM. CEST contrast based on MTR_asym (C): Same ROIs illustrated in green for improved visualization. Z-spectrum (D) and asymmetry analysis (E) shown. Analyses of Z-spectra reveals that a decrease of NOE upfield effects at −3.3 ppm causes the hyperintense MTR_asym contrast in the tumor regions, while no clear APT peak around +3.3 ppm could be identified in any of the analyzed tissues. Even though MTR_asym shows high intensities both in CSF and isolated CEST HIR within CE-T1 tumor, Z-spectrum analysis reveals that the underlying asymmetry has a different origin: no saturation transfer is apparent in CSF at ±3.3 ppm (D black line) while in tumor regions (D dark green, dark blue and light blue lines) MTR_asym = 0 reflects that NOE signals (−3.3 ppm) and saturation transfer effects at the opposite side of the Z-spectrum (+3.3 ppm) are of equal size. Furthermore the width of the Z-spectrum of CSF is decreased due to the longer T2 relaxation time.</p

Boxplots of MTR_Asym quantification from regions of interest (ROI) analysis over all glioblastoma patients.

<p>Boxplots of mean MTR_Asym values on CEST contrast over all patients (N = 12). Overall mean MTR_asym (red stars) and outliers (red crosses) are additionally illustrated. MTR_asym values in all tumor areas (CE-T1 tumor, isolated CEST HIR in CE-T1 tumor, tumor necrosis) and CSF are significantly higher than in CLNAWM (p<0.001). Average signal intensity in PTCH within T2 edema margins is significantly higher (p<0.001) than in CLNAWM and significantly lower (p = 0.015) than in CE-T1 tumor and tumor necrosis (p<0.001). The whiskers of the boxplot for isolated CEST HIR indicate a high variance within this group, which is due to smaller ROI size and the fact that the isolated CEST HIR were visually selected relative to surrounding signal intensity in CE-T1 tumor.</p

Tumor satellite lesion displays hyperintense on NOE mediated CEST.

<p>Tumor satellite of a glioblastoma subcortical temporal right in a 67 year old woman. The satellite presents a clear enhancement on CE-T1 (arrow in A) and barely displays on the T2-weighted image (arrow in B). In contrast, the satellite displays clearly hyperintense on CEST based on MTR_asym (C) and matches with the area of contrast enhancement on the CE-T1 image (A). Furthermore also CSF in lateral ventricles and cerebral sulci displays hyperintense on MTR_asym.</p

Qualitative analyses of NOE-mediated CEST contrast on 3D co-registered data.

<p>Peritumoral hyperintensity: Comparison of the extent of the peritumoral hyperintensity on CEST and T2-weighted images (smaller* = total extent smaller on CEST contrast but exceeding the margins of the T2 edema in one direction). <b>Appearance of isolated high intensity regions (HIR) on MTR_asym</b>: Evaluation if isolated CEST HIR on MTR_asym displayed in the area of CE-T1 tumor or T2 peritumoral edema (Y = Yes, N = No). <b>Satellite lesions</b>: Fraction of contrast enhanced satellite lesions identified on CE-T1 images that were also clearly hyperintense on CEST (∅ = no satellite lesion detected).</p

Peritumoral hyperintensity on NOE mediated CEST compared to standard MRI.

<p>Left frontal glioblastoma in a 59 year old man at 3 Tesla, CE-T1 (A) and T2-weighted images (B). On the selected slice the CEST contrast at 7 Tesla, based on MTR_asym (C), displays peritumoral hyperintensities at equal extent compared to the edema on T2-weighted images. In contrast to T2-weighted images, the CEST peritumoral hyperintensity displays an irregular border and subareas of different signal intensity.</p