title: Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.
abstract: OBJECTIVE
  Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown.
  
  
  METHODS
  Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose.
  
  
  RESULTS
  DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P < 0.005). Both CEST and relaxation effects contribute to the signal change.
  
  
  CONCLUSIONS
  DGE MRI is a feasible technique for studying brain tumor enhancement reflecting differences in tumor blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Kannie W Y
authors.initials: KW
authors.lastname: Chan
authors.affiliation: Department of Medical Radiation Physics, Lund University, Lund, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Knutsson
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Division of Cancer Imaging Research and JHU In Vivo Cellular Molecular Imaging Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Xu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Guanshu
authors.initials: G
authors.lastname: Liu
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Division of Cancer Imaging Research and JHU In Vivo Cellular Molecular Imaging Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Life Science Tokyo Advanced Research Center, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Neurology, Oncology, and Neuroscience, The Johns Hopkins Medicine, and The Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA.
authors.forename: Bachchu
authors.initials: B
authors.lastname: Lal
authors.affiliation: Department of Neurology, Oncology, and Neuroscience, The Johns Hopkins Medicine, and The Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Laterra
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001810:Blood Volume; D001811:Blood Volume Determination / Q000379:methods*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D018810:Magnetic Resonance Angiography / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D005947:Glucose
keywords: D-glucose; brain cancer; chemical exchange saturation transfer (CEST); dynamic glucose enhanced MRI