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Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma
Author(s) -
Linnik Inna V.,
Scott Marietta L. J.,
Holliday Katherine F.,
Woodhouse Neil,
Waterton John C.,
O'Connor James P. B.,
Barjat Hervé,
Liess Carsten,
Ulloa Jose,
Young Helen,
Dive Caroline,
Hodgkinson Cassandra L.,
Ward Tim,
Roberts Darren,
Mills Samantha J.,
Thompson Gerard,
Buonaccorsi Giovanni A.,
Cheung Susan,
Jackson Alan,
Naish Josephine H.,
Parker Geoff J.M.
Publication year - 2014
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.24826
Subject(s) - magnetic resonance imaging , glioma , hypoxia (environmental) , tumor hypoxia , imaging biomarker , medicine , pathology , gadolinium , cd31 , glioblastoma , perfusion , brain tumor , nuclear medicine , immunohistochemistry , chemistry , radiology , cancer research , oxygen , radiation therapy , organic chemistry
Purpose There is a clinical need for noninvasive, nonionizing imaging biomarkers of tumor hypoxia and oxygenation. We evaluated the relationship of T 1 ‐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. Methods Preclinical 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 R 1 curve for OE‐MRI and the gadolinium concentration curve for DCE‐MRI. Clinical evaluation in five patients used analogous imaging protocols and analyses. Results Changes in AUC of OE‐MRI (AUC OE ) signal were regionally heterogeneous across all U87MG tumors. Tumor regions with negative AUC OE 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. Conclusion These data support further investigation of T 1 ‐weighted OE‐MRI to identify regional tumor hypoxia. The quantification of AUC OE has translational potential as a clinical biomarker of hypoxia. Magn Reson Med 71:1854–1862, 2014. © 2013 Wiley Periodicals, Inc.