title: Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.
abstract: OBJECTIVE
  Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization.
  
  
  METHODS
  We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections.
  
  
  RESULTS
  In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology.
  
  
  CONCLUSIONS
  Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.
authors.affiliation: Clinic of Radiology and Neuroradiology, University Medical Center, Schleswig Holstein, Christian Albrechts University, Kiel, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Huhndorf
authors.affiliation: Clinic of Radiology and Neuroradiology, University Medical Center, Schleswig Holstein, Christian Albrechts University, Kiel, Germany.|Molecular Imaging North Competence Center, Christian Albrechts University, Kiel, Germany.|German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Moussavi
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kramann
authors.affiliation: Clinic of Radiology and Neuroradiology, University Medical Center, Schleswig Holstein, Christian Albrechts University, Kiel, Germany.|Molecular Imaging North Competence Center, Christian Albrechts University, Kiel, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Will
authors.affiliation: Institute of Anatomy, Christian Albrechts University, Kiel, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hattermann
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.affiliation: Clinic of Radiology and Neuroradiology, University Medical Center, Schleswig Holstein, Christian Albrechts University, Kiel, Germany.
authors.forename: Olav
authors.initials: O
authors.lastname: Jansen
authors.affiliation: Clinic of Radiology and Neuroradiology, University Medical Center, Schleswig Holstein, Christian Albrechts University, Kiel, Germany.|Molecular Imaging North Competence Center, Christian Albrechts University, Kiel, Germany.|German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.|Faculty for Biology and Psychology, Goettingen University, Goettingen, Germany.
authors.forename: Susann
authors.identifier: http://orcid.org/0000-0003-2792-7423
authors.initials: S
authors.lastname: Boretius
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002199:Capillary Permeability; D003287:Contrast Media / Q000378:metabolism*; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media