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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



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-84875717479   37 Citations


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.

Author List

LaViolette PS, Cohen AD, Prah MA, Rand SD, Connelly J, Malkin MG, Mueller WM, Schmainda KM


Jennifer M. Connelly MD Professor in the Neurology department at Medical College of Wisconsin
Peter LaViolette PhD Associate Professor in the Radiology department at Medical College of Wisconsin
Wade M. Mueller MD Professor in the Neurosurgery department at Medical College of Wisconsin
Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Brain Neoplasms
Contrast Media
Follow-Up Studies
Magnetic Resonance Imaging
Neoplasm Grading
Neovascularization, Pathologic
Retrospective Studies
Survival Rate
Wavelet Analysis