Diagnostic and Prognostic Value of pH- and Oxygen-Sensitive Magnetic Resonance Imaging in Glioma: A Retrospective Study

SIMPLE SUMMARY: Gliomas are known to present with an altered metabolic phenotype that contributes to the abnormal tumor microenvironment detectable on MRI. The aim of this study was to quantify metabolic statuses of glioma using pH- and oxygen-sensitive MRI and associate the measurements with genetic mutation and prognosis. Using the data of 159 adult glioma patients, we revealed that isocitrate dehydrogenase mutation, 1p/19q co-deletion, and epidermal growth factor receptor amplification statuses were associated with the MRI measurements revealing tissue acidosis and hypoxia, and these measurements were also associated with progression-free survival and overall survival, independent of patient age, treatment status, and isocitrate dehydrogenase mutation status. In conclusion, the pH- and oxygen-sensitive MRI is clinically feasible and potentially valuable for distinguishing glioma genotypes and provides additional prognostic value to clinical practice. ABSTRACT: Characterization of hypoxia and tissue acidosis could advance the understanding of glioma biology and improve patient management. In this study, we evaluated the ability of a pH- and oxygen-sensitive magnetic resonance imaging (MRI) technique to differentiate glioma genotypes, including isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, and epidermal growth factor receptor (EGFR) amplification, and investigated its prognostic value. A total of 159 adult glioma patients were scanned with pH- and oxygen-sensitive MRI at 3T. We quantified the pH-sensitive measure of magnetization transfer ratio asymmetry (MTR(asym)) and oxygen-sensitive measure of R(2)’ within the tumor region-of-interest. IDH mutant gliomas showed significantly lower MTR(asym) × R(2)’ (p < 0.001), which differentiated IDH mutation status with sensitivity and specificity of 90.0% and 71.9%. Within IDH mutants, 1p/19q codeletion was associated with lower tumor acidity (p < 0.0001, sensitivity 76.9%, specificity 91.3%), while IDH wild-type, EGFR-amplified gliomas were more hypoxic (R(2)’ p = 0.024, sensitivity 66.7%, specificity 76.9%). Both R(2)’ and MTR(asym) × R(2)’ were significantly associated with patient overall survival (R(2)’: p = 0.045; MTR(asym) × R(2)’: p = 0.002) and progression-free survival (R(2)’: p = 0.010; MTR(asym) × R(2)’: p < 0.0001), independent of patient age, treatment status, and IDH status. The pH- and oxygen-sensitive MRI is a clinically feasible and potentially valuable imaging technique for distinguishing glioma subtypes and providing additional prognostic value to clinical practice.