title: Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma.
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.
authors: Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. plaviole@mcw.edu
authors: Peter S
authors: PS
authors: LaViolette
authors: Alex D
authors: AD
authors: Cohen
authors: Melissa A
authors: MA
authors: Prah
authors: Scott D
authors: SD
authors: Rand
authors: Jennifer
authors: J
authors: Connelly
authors: Mark G
authors: MG
authors: Malkin
authors: Wade M
authors: WM
authors: Mueller
authors: Kathleen M
authors: KM
authors: Schmainda
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003287:Contrast Media; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D058067:Wavelet Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab
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