title: Blood oxygenation level dependent, blood volume, and blood flow responses to carbogen and hypoxic hypoxia in 9L rat gliomas as measured by MRI.
abstract: OBJECTIVE
  To study vascular responsiveness to hypoxia and hypercarbia together with vessel size index (VSI) in a 9L rat glioma (n = 11) using multimodal MRI.
  
  
  METHODS
  VSI was determined using T2 and T2* MRI following AMI-227 contrast agent. Blood oxygenation level dependent (BOLD) signal response was determined using T2 EPI MRI, blood volume changes using AMI-227 and blood flow by means of continuous arterial spin labeling.
  
  
  RESULTS
  VSI in the cortex, tumor rim, and core of 2.2 ± 1.0, 18.2 ± 5.4, and 23.9 ± 14.7 μm, respectively, showing a larger average vessel size in glioma than in the brain parenchyma. BOLD and blood volume signal changes to hypoxia and hypercapnia were much more profound in the tumor rim than the core. Hypoxia led to rim BOLD signal change that was larger in amplitude and it attained the low value much faster than either core or brain cortex. The vasculature in the rim appears more responsive to respiratory challenges in terms of volume adaptation than the core. Blood flow values within the gliomas were much lower than in the contralateral brain. Neither hypercarbia nor hypoxia had an effect on the tumor blood flow.
  
  
  CONCLUSIONS
  Vascular responses of 9L gliomas to respiratory challenge, in particular hypoxia, are heterogeneous between the core and rim zones, potentially offering a means to classify and separate intratumor tissues with differing hemodynamic characteristics.
authors.affiliation: Biomedical NMR Research Center, Department of Radiology, Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Jerome
authors.forename: S Khan
authors.initials: SK
authors.lastname: Hekmatyar
authors.forename: Risto A
authors.initials: RA
authors.lastname: Kauppinen
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D002245:Carbon Dioxide / Q000737:chemistry*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D004058:Diffusion; D005910:Glioma / Q000473:pathology*; D006439:Hemodynamics; D006935:Hypercapnia / Q000097:blood; D000860:Hypoxia / Q000097:blood / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D010100:Oxygen / Q000097:blood* / Q000737:chemistry; D011446:Prospective Studies; D051381:Rats; D011916:Rats, Inbred F344; D013113:Spin Labels
chemical_list: D003287:Contrast Media; D013113:Spin Labels; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen
keywords: 9L glioma; MRI; blood flow; blood oxygenation level dependent signal; blood volume; hypercarbia; hypoxia; vessel size