MR-based hypoxia measures in human glioma

J Neurooncol. 2013 Nov;115(2):197-207. doi: 10.1007/s11060-013-1210-7. Epub 2013 Aug 7.

Abstract

Hypoxia plays a central role in tumor stem cell genesis and is related to a more malignant tumor phenotype, therapy resistance (e.g. in anti-angiogenic therapies) and radio-insensitivity. Reliable hypoxia imaging would provide crucial metabolic information in the diagnostic work-up of brain tumors. In this study, we applied a novel BOLD-based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients and investigated potential benefits and drawbacks. Forty-five glioma patients were examined preoperatively in a pilot study on a 3T MR scanner. rOEF was calculated from quantitative transverse relaxation rates (T2, T2*) and cerebral blood volume (CBV) using a quantitative BOLD approach. rOEF maps were assessed visually and by means of a volume of interest (VOI) analysis. In six cases, MRI-targeted biopsy samples were analyzed using HIF-1α-immunohistochemistry. rOEF maps could be obtained with a diagnostic quality. Focal spots with high rOEF values were observed in the majority of high-grade tumors but in none of the low-grade tumors. VOI analysis revealed potentially hypoxic tumor regions with high rOEF in contrast-enhancing tumor regions as well as in the non-enhancing infiltration zone. Systematic bias was found as a result of non-BOLD susceptibility effects (T2*) and contrast agent leakage affecting CBV. Histological samples demonstrated reasonable correspondence between MRI characteristics and HIF-1α-staining. The presented method of rOEF imaging is a promising tool for the metabolic characterization of human glioma. For the interpretation of rOEF maps, confounding factors must be considered, with a special focus on CBV measurements in the presence of contrast agent leakage. Further validation involving a bigger cohort and extended immuno-histochemical correlation is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / metabolism
  • Cell Hypoxia*
  • Cerebrovascular Circulation*
  • Contrast Media
  • Follow-Up Studies
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • Magnetic Resonance Imaging*
  • Oxygen / analysis*
  • Pilot Projects
  • Radiopharmaceuticals

Substances

  • Contrast Media
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Radiopharmaceuticals
  • Oxygen