Detecting isocitrate dehydrogenase gene mutations in oligodendroglial tumors using diffusion tensor imaging metrics and their correlations with proliferation and microvascular density

J Magn Reson Imaging. 2016 Jan;43(1):45-54. doi: 10.1002/jmri.24958. Epub 2015 May 27.

Abstract

Purpose: Isocitrate dehydrogenase (IDH) mutations are frequently present in oligodendroglial tumors (OTs) and have prognostic value. We assessed whether diffusion tensor imaging (DTI) metrics could aid the noninvasive detection of IDH mutations and their correlations with tumor proliferation and microvascular density (MVD) in OTs.

Materials and methods: Ninety patients with OTs who underwent conventional magnetic resonance imaging (MRI) and DTI were retrospectively reviewed (3T). IDH mutations were determined by immunohistochemical staining or direct sequencing. MVD and cell proliferation were evaluated by immunohistochemical staining with anti-CD31 and Ki-67, respectively. The Mann-Whitney U-test was applied to each of the imaging parameters. Spearman correlation analysis and receiver operating characteristic curve analysis were performed.

Results: The maximal fractional anisotropy (FA), ratio of maximal FA (rmFA), minimal ADC, and ratio of minimal (rmADC) values were demonstrated to be significantly different between the OTs with IDH1/2 mutations and those without mutations (P < 0.05). The areas under the curve (AUCs) for the maximal FA, rmFA, minimal ADC, and rmADC were 0.79, 0.82, 0.77, and 0.80, respectively. A combination rmFA and rmADC for the diagnosis of IDH1/2 mutations led to sensitivity, specificity, and AUC of 91.5%, 76.5%, and 0.86, respectively. The Ki-67 and MVD levels in the IDH-mutated samples were lower than those in the IDH wildtype cases (P < 0.05).

Conclusion: DTI metrics may provide a noninvasive method for assessing the IDH statuses of OTs. Significantly higher minimal ADC and lower maximal FA in OTs with IDH mutations may suggest that IDH mutations lead to proliferation inhibition and an angiogenesis decrease.

Keywords: cell proliferation; diffusion tensor imaging; isocitrate dehydrogenase gene; microvascular density; oligodendroglial tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Cell Proliferation
  • Diffusion Tensor Imaging / methods*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Mutation / drug effects
  • Neoplasm Invasiveness
  • Oligodendroglioma / diagnosis*
  • Oligodendroglioma / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Statistics as Topic

Substances

  • Biomarkers, Tumor
  • Isocitrate Dehydrogenase