Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma

Neuro Oncol. 2013 Apr;15(4):442-50. doi: 10.1093/neuonc/nos323. Epub 2013 Feb 3.

Abstract

Background: Standard pre- and postcontrast (T1 + C) anatomical MR imaging is proving to be insufficient for accurately monitoring bevacizumab treatment response in recurrent glioblastoma (GBM). We present a novel imaging biomarker that detects abnormal tumor vasculature exhibiting both arterial and venous perfusion characteristics. We hypothesized that a decrease in the extent of this abnormal vasculature after bevacizumab treatment would predict treatment efficacy and overall survival.

Methods: Dynamic susceptibility contrast perfusion MRI was gathered in 43 patients with high-grade glioma. Independent component analysis separated vasculature into arterial and venous components. Voxels with perfusion characteristics of both arteries and veins (ie, arterio-venous overlap [AVOL]) were measured in patients with de novo untreated GBM and patients with recurrent high-grade glioma before and after bevacizumab treatment. Treated patients were separated on the basis of an increase or decrease in AVOL volume (+/-ΔAVOL), and overall survival following bevacizumab onset was then compared between +/-ΔAVOL groups.

Results: AVOL in untreated GBM was significantly higher than in normal vasculature (P < .001). Kaplan-Meier survival curves revealed a greater median survival (348 days) in patients with GBM with a negative ΔAVOL after bevacizumab treatment than in patients with a positive change (197 days; hazard ratio, 2.51; P < .05). Analysis of patients with combined grade III and IV glioma showed similar results, with median survivals of 399 days and 153 days, respectively (hazard ratio, 2.71; P < .01). Changes in T1+C volume and ΔrCBV after treatment were not significantly different across +/-ΔAVOL groups, and ΔAVOL was not significantly correlated with ΔT1+C or ΔrCBV.

Conclusions: The independent component analysis dynamic susceptibility contrast-derived biomarker AVOL adds additional information for determining bevacizumab treatment efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Contrast Media*
  • Follow-Up Studies
  • Glioblastoma / blood supply
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging*
  • Neoplasm Grading
  • Neovascularization, Pathologic / diagnosis*
  • Neovascularization, Pathologic / mortality
  • Neovascularization, Pathologic / prevention & control
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Wavelet Analysis*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Contrast Media
  • Bevacizumab