7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors

Abstract

(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.

Keywords: 7T; MR spectroscopy; MRSI; PET; choline; gliomas; glutamine; glycine.

Figure 1

Overview of evaluation results as boxplots for the TSEG1.6 VOI definition. (A,B) DSCs for the comparison of MRSI ratios to PET and the T-segmentation. (C) CoI distance and (D) VOI volume. (E) Median ratios and (F) the calculated VOI thresholds. Gln/tNAA ratios show the best correspondence to PET. Key to the plot: Cross, mean; line, median; box, 2nd–3rd quartiles; whiskers, 1st and 4th quartiles.

Figure 2

Histograms of the DCSs between PET TBR and Gln/tNAA for all six VOI definitions add to the finding that the TSEG1.15 and PSEG1.15 cases (A,B) were not as specific as the other two thresholds. The difference between 1.6 (C,D) and 2.0 (E,F) as cutoff appeared smaller.

Figure 3

Overview of metabolic ratio images, PET TBR images, and the different applied thresholds, together with tumor segmentation for four patients. Heterogeneity between the different ratio maps is quite visible, as are the differences between cutoff values. The actual evaluation as performed only within the defined tumor segmentations is shown in green. PET maps were resampled to MRSI resolution.

Figure 4

Example images of a patient with a high intratumoral correspondence between PET and MRSI ratios to tNAA (DSCs for TSEG1.6: 0.91/0.89/0.88/0.54 for tCho/Gln/Gly/Ins). Notably, the difference between the 1.6 and 2.0 cutoffs for the MRSI ratios is minimal. The actual evaluation as performed only within the defined tumor segmentations is shown in green. PET maps were resampled to MRSI resolution. Red lines indicate slice positions.

Figure 5

Example images of a patient with a low-to-moderate intratumoral correspondence between PET and MRSI ratios to tCr. While Gln/tCr and Gly/tCr align most directly with MET (DSCs for TSEG1.6: 0.59 and 0.55), tCho/tCr extends clearly beyond (DSC for TSEG1.6: 0.25), and Ins/tCr is located only more basally (DSC for TSEG1.6: 0.13). The actual evaluation as performed only within the defined tumor segmentations is shown in green. PET maps were resampled to MRSI resolution.

Figure 6

Correlation matrix for the TSEG1.6 VOI. An expected negative correlation between distance and the other parameters is the most visible feature. All correlation matrices are presented with higher readability in the supplementary data.