CT perfusion with acetazolamide challenge in C6 gliomas and angiogenesis

PLoS One. 2015 Mar 17;10(3):e0121631. doi: 10.1371/journal.pone.0121631. eCollection 2015.

Abstract

Background: This study was performed to investigate the correlation between CT perfusion with acetazolamide challenge and angiogenesis in C6 gliomas.

Methods: Thirty-two male Sprague-Dawley rats were evaluated. The rats were divided randomly to four groups: eight rats with orthotopically implanted C6 gliomas at 10-days old (Group A), eight rats with gliomas at 14-days old (Group B), eight rats with gliomas at 18-days old (Group C), eight rats with orthotopically injected normal saline served as controls. CT perfusion was performed before and after administration of acetazolamide. Changes in perfusion parameters due to acetazolamide administration were calculated and analyzed.

Results: Elevated carbon dioxide partial pressure and decreased pH were found in all 32 rats post acetazolamide challenge (P<0.01). Cerebral blood flow(pre-challenge) was increased in group C (95.0±2.5 ml/100 g/min), as compared to group B (80.1±11.3 ml/100 g/min) and group A (63.1±2.1 ml/100 g/min). Cerebral blood flow percentage changes were detected with a reduction in group C (54.2±4.8%) as compared to controls (111.3±22.2%). Cerebral blood volume(pre-challenge) was increased in group C (50.8±1.7 ml/100 g), as compared to group B (45.7±1.9 ml/100 g) and group A (38.2±0.8 ml/100 g). Cerebral blood volume percentage changes were decreased in group C (23.5±4.6%) as compared to controls (113.5±30.4%). Angiogenesis ratio = [(CD105-MVD) / (FVIII-MVD)] ×100%. Positive correlations were observed between CD105-microvessel density, angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flow(pre-challenge), cerebral blood volume(pre-challenge). Negative correlations were observed between CD105-microvessel density and cerebral blood flow percentage changes (P<0.01, correlation coefficient r=-0.788), cerebral blood volume percentage changes (P<0.01, r=-0.703). Negative correlations were observed between angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flow percentage changes, cerebral blood volume percentage changes.

Conclusion: Our findings suggest that CT perfusion with challenge can provide new insight into non-invasive assessment of rat C6 glioma angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / pharmacology*
  • Animals
  • Blood Flow Velocity / drug effects
  • Cell Line, Tumor
  • Cerebral Angiography
  • Cerebrovascular Circulation / drug effects*
  • Glioma / blood supply*
  • Glioma / diagnostic imaging*
  • Male
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / diagnostic imaging*
  • Neovascularization, Pathologic / diagnostic imaging*
  • Rats
  • Rats, Sprague-Dawley
  • Tomography, X-Ray Computed

Substances

  • Acetazolamide

Grants and funding

This work was supported by National Natural Science Foundations of China (Grant No. 30970805, 81400428), a grant from Science and Technology Commission of Shanghai Municipality (Grant No. 09JC1403100), Shanghai Municipality Commission of Health and Family Planning Projects (Grant No. 2011-187), a grant from Shanghai Jinshan Municipality Health Bureau Youth Foundation (Grant No. JWKJ-KTYQ-201202, JWKJ-RCYQ-201202.) The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.