DCE-MRI in Human Gliomas: A Surrogate for Assessment of Invasive Hypoxia Marker HIF-1Α Based on MRI-Neuronavigation Stereotactic Biopsies

Abstract

The purpose of this study was to correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with data from a specific marker of hypoxia, hypoxia-inducible factor 1α (HIF-1α), in human gliomas on a point-to-point basis by using coregistered magnetic resonance imaging and frameless stereotactic biopsies. Thirty-four patients with treatment-naive gliomas underwent DCE, axial T1-weighted, T2-weighted, T2-weighted fluid acquisition of inversion recovery, and three-dimensional T1-weighted brain volume with gadolinium contrast enhancement sequences on a 3.0-T magnetic resonance scanner before stereotactic surgery. Quantitative perfusion indices such as endothelial transfer constant, fractional extravascular extracellular space volume, fractional plasma volume, and reflux rate were measured at corresponding stereotactic biopsy sites. Each sample was considered an independent measurement, and its histology grade was diagnosed. HIF-1α expression was quantified from the point-to-point biopsy tissues. Analyses of receiver operating characteristic curves were done for HIF-1α to discriminate different grades of glioma. To look for correlations between immunohistochemical parameters and DCE indices, Spearman's correlation coefficient was used. Seventy biopsy samples from 34 subjects were included in the analysis. Mean immunoreactivity scores of HIF-1α were 2.75 ± 1.11 for grade II (n = 24), 6.20 ± 2.33 for grade III (n = 20), and 10.46 ± 2.42 for grade IV (n = 26). HIF-1α showed very good-to-excellent accuracy in discriminating grade II from III, III from IV, and II from IV (area under the curve = 0.838, 0.862, and 0.994, respectively). Endothelial transfer constant and fractional extravascular extracellular space volume showed a significantly positive correlation with HIF-1α expression (r = 0.686, P < .001; r = 0.549, P < .001, respectively). Our study demonstrated HIF-1α to be a significant predictor of different grades of gliomas with high sensitivity and specificity. DCE-MRI is a useful, noninvasive imaging tool for quantitative evaluation of HIF-1α, and its parameters may be used as a surrogate for HIF-1α expression.