Abstract #0398

Differentiation of IDH1 mutant and wild-type gliomas based on metabolic signatures obtained from pH- and oxygen-sensitive molecular MRI

Jingwen Yao^1,2,3, Ararat Chakhoyan^1,3, Catalina Raymond^1,3, Noriko Salamon³, Linda Liau^4,5, William Yong^6,7, Phioanh Nghiemphu⁸, Albert Lai^5,8, Whitney Pope³, Timothy Cloughesy⁸, and Benjamin Ellingson^1,2,3,5,9,10

¹Brain Tumor Imaging Laboratory (BTIL), Center of Computer Vision and Imaging Biomarker, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ²Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California, Los Angeles, Los Angeles, CA, United States, ³Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁴Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁵UCLA Brain Research Institute (BRI), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁶Brain Tissue Translational Resource (BTTR), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁷Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁸Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁹Physics and Biology in Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ¹⁰Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States

In the current study, we have demonstrated that pH- and oxygen-sensitive amine CEST-SAGE-EPI (chemical exchange saturation transfer spin-and-gradient-echo echoplanar imaging) is a clinically feasible, powerful imaging technique for distinguishing between IDH1-mutant and wild-type gliomas. Results suggest that IDH1 mutation is associated with lower MTR_asym at 3.0ppm and lower R₂’, implying lower acidity and vascular hypoxia. We hypothesize that 2-HG produced by IDH1-mutant activates PHD and the degradation of HIF1α, subsequently preventing a metabolic shift from oxidative phosphorylation to glycolysis. This is supported by our histological findings of loss of correlation between levels of hypoxia and HIF1α tissue expression in IDH1 mutants.

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