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01-11-2013 | Clinical Study

MR-based hypoxia measures in human glioma

Authors: Vivien Tóth, Annette Förschler, Nuria M. Hirsch, Jürgen den Hollander, Hendrik Kooijman, Jens Gempt, Florian Ringel, Jürgen Schlegel, Claus Zimmer, Christine Preibisch

Published in: Journal of Neuro-Oncology | Issue 2/2013

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.

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Title: MR-based hypoxia measures in human glioma
Authors: Vivien Tóth
Annette Förschler
Nuria M. Hirsch
Jürgen den Hollander
Hendrik Kooijman
Jens Gempt
Florian Ringel
Jürgen Schlegel
Claus Zimmer
Christine Preibisch
Publication date: 01-11-2013
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-013-1210-7

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MR-based hypoxia measures in human glioma

Abstract

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