Abstract
Co-deletion of 1p/19q is a hallmark of oligodendroglioma and predicts better survival. However, little is understood about its metabolic characteristics. In this study, we aimed to explore the extracellular acidity of WHO grade II and III gliomas associated with 1p/19q co-deletion. We included 76 glioma patients who received amine chemical exchange saturation transfer (CEST) imaging at 3 T. Magnetic transfer ratio asymmetry (MTRasym) at 3.0 ppm was used as the pH-sensitive CEST biomarker, with higher MTRasym indicating lower pH. To control for the confounder factors, T2 relaxometry and l-6-18F-fluoro-3,4-dihydroxyphenylalnine (18F-FDOPA) PET data were collected in a subset of patients. We found a significantly lower MTRasym in 1p/19q co-deleted gliomas (co-deleted, 1.17% ± 0.32%; non-co-deleted, 1.72% ± 0.41%, P = 1.13 × 10−7), while FDOPA (P = 0.92) and T2 (P = 0.61) were not significantly affected. Receiver operating characteristic analysis confirmed that MTRasym could discriminate co-deletion status with an area under the curve of 0.85. In analysis of covariance, 1p/19q co-deletion status was the only significant contributor to the variability in MTRasym when controlling for age and FDOPA (P = 2.91 × 10−3) or T2 (P = 8.03 × 10−6). In conclusion, 1p/19q co-deleted gliomas were less acidic, which may be related to better prognosis. Amine CEST-MRI may serve as a non-invasive biomarker for identifying 1p/19q co-deletion status.
Highlights
The role of molecular markers in stratifying brain tumors has gained increasing awareness in the past decade
From the Bloch-McConnell simulation result, we observed that MTRasym, as a measure of chemical exchange saturation transfer (CEST) contrast, demonstrated sensitivity to pH, amine concentration, and tissue T 2. MTRasym at 3.0 ppm increased with decreasing pH, peaking around pH 5.5–6.0 (Fig. 1)
Results confirmed that CEST contrast measured as MTRasym at 3.0 ppm has similar dependence pattern for two different α-amino acids, glycine and phenylalanine, indicating that 18F-FDOPA can serve as a surrogate marker of tissue amine concentration
Summary
The role of molecular markers in stratifying brain tumors has gained increasing awareness in the past decade. In 2016, the World Health Organization (WHO) has revised the classification criteria of gliomas to incorporate molecular markers into diagnosis, instead of relying solely on histological p henotypes[1]. In this updated guideline, the definition of oligodendroglioma is defined by two genotypic features: the mutation in isocitrate dehydrogenase (IDH), as well as the co-deletion of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q). The histopathological diagnosis of oligoastrocytoma, which suffered from high interobserver discordance, has been largely abandoned with the adoption of the more robust molecular classification. In addition to its diagnostic value, 1p/19q co-deletion is associated with better response to radiotherapy and alkylating agent chemotherapy, and longer progression-free and overall survival[4]
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