• Magn Reson Med · May 2014

    Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.

    • Inna V Linnik, Marietta L J Scott, Katherine F Holliday, Neil Woodhouse, John C Waterton, James P B O'Connor, Hervé Barjat, Carsten Liess, Jose Ulloa, Helen Young, Caroline Dive, Cassandra L Hodgkinson, Tim Ward, Darren Roberts, Samantha J Mills, Gerard Thompson, Giovanni A Buonaccorsi, Susan Cheung, Alan Jackson, Josephine H Naish, and Geoff J M Parker.
    • Centre for Imaging Sciences, The University of Manchester, Manchester, UK; University of Manchester Biomedical Imaging Institute, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.
    • Magn Reson Med. 2014 May 1;71(5):1854-62.

    PurposeThere is a clinical need for noninvasive, nonionizing imaging biomarkers of tumor hypoxia and oxygenation. We evaluated the relationship of T1 -weighted oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements to histopathology measurements of tumor hypoxia in a murine glioma xenograft and demonstrated technique translation in human glioblastoma multiforme.MethodsPreclinical evaluation was performed in a subcutaneous murine human glioma xenograft (U87MG). Animals underwent OE-MRI followed by dynamic contrast-enhanced MRI (DCE-MRI) and histological measurement including reduced pimonidazole adducts and CD31 staining. Area under the curve (AUC) was measured for the R1 curve for OE-MRI and the gadolinium concentration curve for DCE-MRI. Clinical evaluation in five patients used analogous imaging protocols and analyses.ResultsChanges in AUC of OE-MRI (AUCOE ) signal were regionally heterogeneous across all U87MG tumors. Tumor regions with negative AUCOE typically had low DCE-MRI perfusion, had positive correlation with hypoxic area (P = 0.029), and had negative correlation with vessel density (P = 0.004). DCE-MRI measurements did not relate to either hypoxia or vessel density in U87MG tumors. Clinical data confirmed comparable signal changes in patients with glioblastoma.ConclusionThese data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.Copyright © 2013 Wiley Periodicals, Inc.

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