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

Magn Reson Med. 2014 May;71(5):1854-62. doi: 10.1002/mrm.24826. Epub 2013 Jun 24.


Purpose: There 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.

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 R1 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 (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.

Conclusion: These 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.

Keywords: hypoxia; magnetic resonance imaging; oxygen-enhanced MRI; oxygenation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Hypoxia
  • Cell Line, Tumor
  • Female
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Nude
  • Oximetry / methods*
  • Oxygen / metabolism*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution


  • Biomarkers, Tumor
  • Oxygen