Quantification of serial changes in cerebral blood volume and metabolism in patients with recurrent glioblastoma undergoing antiangiogenic therapy

Eur J Radiol. 2015 Jun;84(6):1128-36. doi: 10.1016/j.ejrad.2015.02.025. Epub 2015 Mar 6.

Abstract

Objectives: To evaluate the usefulness of quantitative advanced magnetic resonance imaging (MRI) methods for assessment of antiangiogenic therapy (AAT) response in recurrent glioblastoma multiforme (GBM).

Methods: Eighteen patients with recurrent GBM received bevacizumab and 18 patients served as control group. Baseline MRI and two follow-up examinations were acquired every 3-5 months using dynamic susceptibility-weighted contrast (DSC) perfusion MRI and (1)H-MR spectroscopic imaging ((1)H-MRSI). Maps of absolute cerebral blood volume (aCBV) were coregistered with choline (Cho) and N-acetyl-aspartate (NAA) concentrations and compared to usually used relative parameters as well as controls.

Results: Perfusion significantly decreased in responding and pseudoresponding GBMs but also in normal appearing brain after AAT onset. Cho and NAA concentrations were superior to Cr-ratios in lesion differentiation and showed a clear gap between responding and pseudoresponding lesions. Responders to AAT exceptionally frequently (6 out of 8 patients) showed remote GBM progression.

Conclusions: Quantification of CBV reveals changes in normal brain perfusion due to AAT, which were not described so far. DSC perfusion MRI seems not to be suitable for differentiation between response and pseudoresponse to AAT. However, absolute quantification of brain metabolites may allow for distinction due to a clear gap at 6-9 months after therapy onset.

Keywords: Antiangiogenic therapy; Cerebral blood volume; MR spectroscopy; Quantitative MR imaging; Recurrent glioblastoma.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / drug effects
  • Aspartic Acid / metabolism
  • Bevacizumab / therapeutic use
  • Blood Volume / drug effects*
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism
  • Brain Mapping
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Cerebrovascular Circulation / drug effects
  • Choline / metabolism
  • Contrast Media / therapeutic use
  • Female
  • Follow-Up Studies
  • Glioblastoma / blood supply
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism*
  • Humans
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood supply
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Reproducibility of Results

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Bevacizumab
  • Aspartic Acid
  • N-acetylaspartate
  • Choline