Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma.

Background Altered metabolism is a characteristic of cancer. Because of a shift in glucose metabolism from oxidative phosphorylation to lactate production for energy generation, malignant tumors are characterized by increased glycolysis followed by lactic acid fermentation, even in the presence of abundant oxygen (the Warburg effect). Purpose To quantitatively investigate dynamic oxygen 17 (17O) MRI in healthy participants and participants with untreated glioma to understand altered cerebral oxygen metabolism in glioma. Materials and Methods In this prospective study conducted from September 2016 to June 2018, individuals with newly diagnosed previously untreated glioma (World Health Organization grade II-IV) and healthy volunteers were included. Dynamic 17O MRI was performed with a 7.0-T whole-body system. 17O2 gas inhalation enabled dynamic measurement of the cerebral metabolic rate of oxygen (CMRO2) consumption. In healthy volunteers and participants with glioma, CMRO2 values in gray matter and white matter volumes were compared by using Wilcoxon signed rank tests. In participants with glioma, the tumor volume and tumor subcompartments were compared with normal-appearing gray matter and white matter by using Friedman test followed by Holm-Sidak post hoc tests. Results Ten participants (mean age, 42 years ± 18 [standard deviation]; nine men) with glioma and three healthy volunteers (mean age, 44 years ± 21; all men) were evaluated. CMRO2 was higher in normal-appearing gray matter compared with white matter in both participants with glioma (2.36 µmol/g/min ± 0.22 vs 0.75 µmol/g/min ± 0.10, respectively) and healthy volunteers (2.38 µmol/g/min ± 0.15 vs 0.63 µmol/g/min ± 0.05, respectively) (P < .001 and P = .03, respectively). In the tumor region, CMRO2 was reduced (high-grade tumor CMRO2, 0.23 µmol/g/min ± 0.07; low-grade tumor CMRO2, 0.39 µmol/g/min ± 0.16; overall CMRO2, 0.34 µmol/g/min ± 0.16) compared with normal-appearing gray matter (P < .001) and normal-appearing white matter (P < .001) in accordance with the Warburg theorem. Conclusion Dynamic oxygen 17 MRI method at 7.0 T as a direct metabolic imaging technique in glioma enabled quantitative visualization of the Warburg effect. A general reduction in oxidative glycolysis was observed in accordance with the Warburg theorem. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Rapalino in this issue.

Relaxation-compensated amide proton transfer (APT) MRI signal intensity is associated with survival and progression in high-grade glioma patients.

OBJECTIVES: The purpose of this study was to investigate the association of relaxation-compensated chemical exchange saturation transfer (CEST) MRI with overall survival (OS) and progression-free survival (PFS) in newly diagnosed high-grade glioma (HGG) patients. METHODS: Twenty-six patients with newly diagnosed high-grade glioma (WHO grades III-IV) were included in this prospective IRB-approved study. CEST MRI was performed on a 7.0-T whole-body scanner. Association of patient OS/PFS with relaxation-compensated CEST MRI (amide proton transfer (APT), relayed nuclear Overhauser effect (rNOE)/NOE, downfield-rNOE-suppressed APT (dns-APT)) and diffusion-weighted imaging (apparent diffusion coefficient) were assessed using the univariate Cox proportional hazards regression model. Hazard ratios (HRs) and corresponding 95% confidence intervals were calculated. Furthermore, OS/PFS association with clinical parameters (age, gender, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status, and therapy: biopsy + radio-chemotherapy vs. debulking surgery + radio-chemotherapy) were tested accordingly. RESULTS: Relaxation-compensated APT MRI was significantly correlated with patient OS (HR = 3.15, p = 0.02) and PFS (HR = 1.83, p = 0.009). The strongest association with PFS was found for the dns-APT metric (HR = 2.61, p = 0.002). These results still stand for the relaxation-compensated APT contrasts in a homogenous subcohort of n = 22 glioblastoma patients with isocitrate dehydrogenase (IDH) wild-type status. Among the tested clinical parameters, patient age (HR = 1.1, p = 0.001) and therapy (HR = 3.68, p = 0.026) were significant for OS; age additionally for PFS (HR = 1.04, p = 0.048). CONCLUSION: Relaxation-compensated APT MRI signal intensity is associated with overall survival and progression-free survival in newly diagnosed, previously untreated glioma patients and may, therefore, help to customize treatment and response monitoring in the future. KEY POINTS: • Amide proton transfer (APT) MRI signal intensity is associated with overall survival and progression in glioma patients. • Relaxation compensation enhances the information value of APT MRI in tumors. • Chemical exchange saturation transfer (CEST) MRI may serve as a non-invasive biomarker to predict prognosis and customize treatment.