Investigation of hypoxia conditions using oxygen-enhanced magnetic resonance imaging measurements in glioma models
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Qi Fan1,*, Cheuk Ying Tang2,*, Di Gu3, Jinyu Zhu1, Guojun Li4, Yingwei Wu1, Xiaofeng Tao1
1Radiology Department, Shanghai People’s Ninth Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
2Radiology Department, Mount Sinai School of Medicine, New York, USA
3Department of Urology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
4Departments of Head and Neck Surgery, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
*These authors have contributed equally to this work
Yingwei Wu, email: firstname.lastname@example.org
Xiaofeng Tao, email: Taoxiaofeng0808@126.com
Keywords: hypoxia, glioma, oxygen-enhanced magnetic resonance imaging, GLUT-1, pO2
Received: December 06, 2016 Accepted: February 20, 2017 Published: March 16, 2017
The objective of this study was to determine whether using oxygen-enhanced magnetic resonance imaging (OE-MRI) to assess hypoxia is feasible and whether historical measurements, pO2 changes, and percentage of signal intensity changes (PSIC) are correlated in an animal model of glioma. A total of 25 Sprague-Dawley rats were used to establish C6 brain or subcutaneous glioma model. Nine rats with brain gliomas underwent OE-MRI followed by histopathologic analysis to assess microvessel density and hypoxia. Another 11 rats were underwent OE-MRI and were followed for a survival analysis. Time–T1-weighted MR signal intensity (SI) curves and PSIC maps were derived from the OE-MRI data. High–regions of interests (ROI-h; PSIC > 10%) and low-ROIs (ROI-l; PSIC < 10%) were defined on the PSIC maps. To validate the PSIC map for identifying tumor hypoxia, we subjected an additional 5 rats with subcutaneous glioma to OE-MRI and pO2 measurements. All tumors showed regional heterogeneity on the PSIC maps. For the brain tumors, the time-SI curves for the ROIs-h showed a greater increase in SI than those for the ROIs-l did. The percentage of tumor area with a low PSIC was significantly correlated with the percentage of hypoxia staining and necrosis (r =0.71; P<0.05). ROIs with a higher PSIC typically had more vessels (r=0.88; P<0.05). A significant difference in survival was shown (log-rank P = 0.035). The time-pO2 curves of the subcutaneous tumors were similar to the time-SI curves. PSIC was significantly correlated with pO2 changes (r =0.82; P<0.05). These findings suggest that OE-MRI measurements can be used to assess hypoxia in C6 glioma models. In these models, the PSIC value was correlated with survival, indicating that PSIC could serve as a prognostic marker for glioma.
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