High-resolution metabolic imaging of high-grade gliomas using 7T-CRT-FID-MRSI

Abstract

Objectives: Successful neurosurgical intervention in gliomas depends on the precision of the preoperative definition of the tumor and its margins since a safe maximum resection translates into a better patient outcome. Metabolic high-resolution imaging might result in improved presurgical tumor characterization, and thus optimized glioma resection. To this end, we validated the performance of a fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in a patient cohort of 23 high-grade gliomas (HGG).

Materials and methods: We preoperatively measured 23 patients with histologically verified HGGs (17 male, 8 female, age 53 ± 15) with an MRSI sequence based on concentric ring trajectories with a 64 × 64 × 39 measurement matrix, and a 3.4 × 3.4 × 3.4 mm³ nominal voxel volume in 15 min. Quantification used a basis-set of 17 components including N-acetyl-aspartate (NAA), total choline (tCho), total creatine (tCr), glutamate (Glu), glutamine (Gln), glycine (Gly) and 2-hydroxyglutarate (2HG). The resultant metabolic images were evaluated for their reliability as well as their quality and compared to spatially segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast enhanced + edema, peritumoral) based on clinical data and also compared to histopathology (e.g., grade, IDH-status).

Results: Eighteen of the patient measurements were considered usable. In these patients, ten metabolites were quantified with acceptable quality. Gln, Gly, and tCho were increased and NAA and tCr decreased in nearly all tumor regions, with other metabolites such as serine, showing mixed trends. Overall, there was a reliable characterization of metabolic tumor areas. We also found heterogeneity in the metabolic images often continued into the peritumoral region. While 2HG could not be satisfyingly quantified, we found an increase of Glu in the contrast-enhancing region of IDH-wildtype HGGs and a decrease of Glu in IDH1-mutant HGGs.

Conclusions: We successfully demonstrated high-resolution 7T 3D-MRSI in HGG patients, showing metabolic differences between tumor regions and peritumoral tissue for multiple metabolites. Increases of tCho, Gln (related to tumor metabolism), Gly (related to tumor proliferation), as well as decreases in NAA, tCr, and others, corresponded very well to clinical tumor segmentation, but were more heterogeneous and often extended into the peritumoral region.

Keywords: 7 Tesla; Concentric circle trajectories; Glycine; High-grade glioma; Magnetic resonance spectroscopic imaging; Metabolic imaging.

Graphical abstract

Fig. 1

Example spectra of two tumor voxels and one NAWM voxel of patient #9. Different metabolic patterns between a tCho and a Gln hotspot are visible. The spectra were phased for display purposes.

Fig. 2

Images of the most reliable metabolites of all primary orientations in patients #2 and #8. Next to the well-researched marker tCho, Gln and Gly also appear to coincide with tumor activity. The red reference lines indicate the positions of the displayed MRSI slices.

Fig. 3

Overview of qualitative trends of metabolic activity per ROI and metabolite. Different bar sizes are attributable to the fact that not all tumor ROIs were present in all cases, combined with the filtering of voxels outside of the defined quality criteria (which would, in some cases, result in a metabolite not being successfully quantified at all in a specific ROI). NEC was segmented, within the MRSI FOV and within the quality criteria in 10 of 18 patients, with CE and NCE respectively in 13 and 17 of the patients. Again, tCho, Gln, and Gly showed a clear overall increase within the segmented tumor region. Many other metabolites showed a mixed behavior and, in many cases, there was also increased metabolic divergence in the peritumoral region.

Fig. 4

Examples of glycine images over multiple patients show a good correspondence to morphological imaging and even more differentiated activity, as in patient #1. The red reference lines indicate the positions of the displayed MRSI slices.

Fig. 5

Compared to a clinical imaging-derived segmentation, tCho, Gln, and Gly images have similar, but more differentiated hotspots which could lead to the development of metabolic regional profiles. The red reference lines indicate the positions of the displayed MRSI slices.

Fig. 6

A comparison of the Glu+Gln and mIns+Gly combined and separated shows the benefit of the 7T spectral resolution that enables the detection of metabolic alterations that would have remained inconspicuous on the sum images. In particular, the Gly hotspot in patient #2 is not apparent on the mIns+Gly image. The red reference lines indicate the positions of the displayed MRSI slices.