title: Simultaneous assessment of vessel size index, relative blood volume, and vessel permeability in a mouse brain tumor model using a combined spin echo gradient echo echo-planar imaging sequence and viable tumor analysis.
abstract: OBJECTIVE
  Combining multiple imaging biomarkers in one magnetic resonance imaging (MRI) session would be beneficial to gain more data pertaining to tumor vasculature under therapy. Therefore, simultaneous measurement of perfusion, permeability, and vessel size imaging (VSI) using a gradient echo spin echo (GE-SE) sequence with injection of a clinically approved gadolinium (Gd)-based contrast agent was assessed in an orthotopic glioma model.
  
  
  METHODS
  A combined spin echo gradient echo echo-planar imaging sequence was implemented using a single contrast agent Gd diethylenetriaminepentaacetic acid (Gd-DTPA). This sequence was tested in a mouse brain tumor model (U87_MG), also under treatment with an antiangiogenic agent (bevacizumab). T2 maps and the apparent diffusion coefficient (ADC) were used to differentiate regions of cell death and viable tumor tissue.
  
  
  RESULTS
  In viable tumor tissue regional blood volume was 5.7 ± 0.6% in controls and 5.2 ± 0.3% in treated mice. Vessel size was 18.1 ± 2.4 μm in controls and 12.8 ± 2.0 μm in treated mice, which correlated with results from immunohistochemistry. Permeability (K(trans) ) was close to zero in treated viable tumor tissue and 0.062 ± 0.024 min(-1) in controls.
  
  
  CONCLUSIONS
  Our MRI method allows simultaneous assessment of several physiological and morphological parameters and extraction of MRI biomarkers for vasculature. These could be used for treatment monitoring of novel therapeutic agents such as antiangiogenic drugs.
authors.affiliation: Department of Radiology Medical Physics, University Medical Center, Freiburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kording
authors.forename: Claudia
authors.initials: C
authors.lastname: Weidensteiner
authors.forename: Stefan
authors.initials: S
authors.lastname: Zwick
authors.forename: Nadja
authors.initials: N
authors.lastname: Osterberg
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
authors.forename: Ori
authors.initials: O
authors.lastname: Staszewski
authors.forename: Dominik
authors.initials: D
authors.lastname: von Elverfeldt
authors.forename: Wilfried
authors.initials: W
authors.lastname: Reichardt
mesh_terms: D000818:Animals; D001810:Blood Volume; D001811:Blood Volume Determination / Q000379:methods; D001932:Brain Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D017352:Echo-Planar Imaging; D005260:Female; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D018810:Magnetic Resonance Angiography; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
keywords: DCE-MRI; antiangiogenic therapy; glioma; vessel size imaging