Nuclear overhauser enhancement mediated chemical exchange saturation transfer imaging at 7 Tesla in glioblastoma patients

Abstract

Background and purpose: Nuclear Overhauser Enhancement (NOE) mediated chemical exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI) technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T) and standard MRI in glioblastoma patients.

Patients and methods: Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee-approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3 ppm (B1 = 0.7 µT) to calculate the magnetization transfer ratio asymmetry (MTR(asym)). Contrast enhanced T1 (CE-T1) and T2-weighted images were acquired at 3T and used for data co-registration and comparison.

Results: Mean NOE mediated CEST signal based on MTR(asym) values over all patients was significantly increased (p<0.001) in CE-T1 tumor (-1.99 ± 1.22%), tumor necrosis (-1.36 ± 1.30%) and peritumoral CEST hyperintensities (PTCH) within T2 edema margins (-3.56 ± 1.24%) compared to contralateral normal appearing white matter (-8.38 ± 1.19%). In CE-T1 tumor (p = 0.015) and tumor necrosis (p<0.001) mean MTR(asym) values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40 ± 2.21%) displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images.

Conclusion: NOE mediated CEST Imaging at 7 T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning.

Figure 1. Peritumoral hyperintensity on NOE mediated CEST compared to standard MRI.

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.

Figure 2. Tumor satellite lesion displays hyperintense on NOE mediated CEST.

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.

Figure 3. Regions of interest (ROI) selection for spectral analysis and MTR_asym quantification.

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.

Figure 4. Boxplots of MTR_Asym quantification from regions of interest (ROI) analysis over all glioblastoma patients.

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.