Abstract

Abstract 1p/19q co-deleted gliomas are known to have slower growth rates and are more sensitive to chemotherapy and radiotherapy. This may be partially explained by the lower tumor acidosis compared to non-co-deleted gliomas, as extracellular acidosis is one of the driving forces toward tumor invasion and resistance to treatments. Amine CEST-EPI is a fast chemical exchange saturation transfer (CEST) imaging technique sensitive to decreased extracellular pH, transverse relaxation rate, and amino acid concentration. In the current study, we demonstrated that 1p/19q co-deleted gliomas are less acidic than non-co-deleted gliomas, using a combination of pH-sensitive amineCEST-EPI, T2 relaxometry, and 18F-FDOPA (18[F] fluorodopa) amino acid PET. 70 histologically-confirmed glioma patients (World Health Organization WHO grade II, N=35; grade III, N=35) received amine CEST-EPI scans. Among them, 16 patients received 18F-FDOPA PET scan and 45 patients received T2 relaxometry quantification. Mann-Whitney u-test is performed to evaluate the differences. Median MTRasym at 3ppm (magnetization transfer ratio asymmetry at amine proton resonance frequency) within T2 hyperintense lesions was significantly lower in 1p/19q co-deleted gliomas compared to non-co-deleted ones (co-deleted 1.19±0.31%; non-co-deleted 1.66±0.45%; p< 0.0001). The significantly lower MTRasym persists when comparing within grade II (p=0.003), grade III (p=0.031), IDH1 mutated gliomas (p=0.002), and gliomas exhibiting classical oligodendroglial histology (p=0.0007). The ROC analysis shows that the prediction of 1p/19q status using MTRasym has area under the curve (AUC) of 0.80 (sensitivity 75.6%. specificity 72.7%). Median FDOPA and T2 in T2-hyperintense lesions were not different between 1p/19q co-deleted and non-co-deleted tumors (FDOPA p=0.84; T2 p=0.63). Results suggest 1p/19q co-deleted gliomas have notably lower acidity compared with non-co-deleted gliomas, as indicated by lower MTRasym and no differences in amino acid concentration or transverse relaxation rate. Further, data indicate the 1p/19q co-deleted gliomas may have distinct metabolic characteristics and tumor microenvironment that can be measured using pH-sensitive amineCEST-MRI at 3T.

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