Relative oxygen extraction fraction (rOEF) MR imaging reveals higher hypoxia in human epidermal growth factor receptor (
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DIAGNOSTIC NEURORADIOLOGY
Relative oxygen extraction fraction (rOEF) MR imaging reveals higher hypoxia in human epidermal growth factor receptor (EGFR) amplified compared with non-amplified gliomas Talia C. Oughourlian 1,2 & Jingwen Yao 1,3 & Akifumi Hagiwara 1,4 & David A. Nathanson 5 & Catalina Raymond 1,4 & Whitney B. Pope 4 & Noriko Salamon 4 & Albert Lai 6,7 & Matthew Ji 6,7 & Phioanh L. Nghiemphu 6,7 & Linda M. Liau 8 & Timothy F. Cloughesy 6,7 & Benjamin M. Ellingson 1,4 Received: 22 July 2020 / Accepted: 13 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Epidermal growth factor receptor (EGFR) amplification promotes gliomagenesis and is linked to lack of oxygen within the tumor microenvironment. Using hypoxia-sensitive spin-and-gradient echo echo-planar imaging and perfusion MRI, we investigated the influence of EGFR amplification on tissue oxygen availability and utilization in human gliomas. Methods This study included 72 histologically confirmed EGFR-amplified and non-amplified glioma patients. Reversible transverse relaxation rate (R2′), relative cerebral blood volume (rCBV), and relative oxygen extraction fraction (rOEF) were calculated for the contrast-enhancing and non-enhancing tumor regions. Using Student t test or Wilcoxon rank-sum test, median R2′, rCBV, and rOEF were compared between EGFR-amplified and non-amplified gliomas. ROC analysis was performed to assess the ability of imaging characteristics to discriminate EGFR amplification status. Overall survival (OS) was determined using univariate and multivariate cox models. Kaplan-Meier survival curves were plotted and compared using the log-rank test. Results EGFR amplified gliomas exhibited significantly higher median R2′ and rOEF than non-amplified gliomas. ROC analysis suggested that R2′ (AUC = 0.7190; P = 0.0048) and rOEF (AUC = 0.6959; P = 0.0156) could separate EGFR status. Patients with EGFR-amplified gliomas had a significantly shorter OS than non-amplified patients. Univariate cox regression analysis determined both R2′ and rOEF significantly influence OS. No significant difference was observed in rCBV between patient cohorts nor was rCBV found to be an effective differentiator of EGFR status. Conclusion Imaging of tumor oxygen characteristics revealed EGFR-amplified gliomas to be more hypoxic and contribute to shorter patient survival than EGFR non-amplified gliomas. Keywords Epidermal growth factor receptor . Glioma . Hypoxia . Relative oxygen extraction fraction . Reversible transverse relaxation rate . Spin-and-gradient echo echo-planar imaging Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00234-020-02585-8) contains supplementary material, which is available to authorized users. * Benjamin M. Ellingson [email protected]
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Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA 90024, USA
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Department of Molecular and Medical P
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