The Role of Amide Proton Transfer (APT)-Weighted Imaging in Glioma: Assessment of Tumor Grading, Molecular Profile and Survival in Different Tumor Components

• Published in: Cancers Vol. 16; no. 17; p. 3014
• Main Authors: Borges de Almeida, Gonçalo, Pascuzzo, Riccardo, Mambrin, Francesca, Aquino, Domenico, Verri, Mattia, Moscatelli, Marco, Del Bene, Massimiliano, DiMeco, Francesco, Silvani, Antonio, Pollo, Bianca, Grisoli, Marina, Doniselli, Fabio Martino
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.08.2024
• Subjects: Brain cancer; Brain tumors; Correspondence; DNA methylation; Glioma; Medical prognosis; Mutation; Peptides; Proteins; Protons; Solid tumors; Spectrum analysis; Tumors; United States > US; Germany; glioblastoma; MGMT; MRI; survival; glioma; IDH; chemical exchange saturation transfer
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16173014

Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas.