Faculty Collaboration Database

Multimodality imaging of abnormal vascular perfusion and morphology in preclinical 9L gliosarcoma model. PLoS One 2011 Jan 31;6(1):e16621

Date

02/10/2011

Pubmed ID

21305001

Pubmed Central ID

PMC3031600

DOI

10.1371/journal.pone.0016621

Scopus ID

2-s2.0-79551648296 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

BACKGROUND: This study demonstrates that a dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) perfusion parameter may indicate vascular abnormality in a brain tumor model and reflects an effect of dexamethasone treatment. In addition, X-ray computed tomography (CT) measurements of vascular tortuosity and tissue markers of vascular morphology were performed to investigate the underpinnings of tumor response to dexamethasone.

METHODOLOGY/PRINCIPAL FINDINGS: One cohort of Fisher 344 rats (N = 13), inoculated intracerebrally with 9L gliosarcoma cells, was treated with dexamethasone (i.p. 3 mg/kg/day) for five consecutive days, and another cohort (N = 11) was treated with equal volume of saline. Longitudinal DSC-MRI studies were performed at the first (baseline), third and fifth day of treatments. Relative cerebral blood volume (rCBV) was significantly reduced on the third day of dexamethasone treatment (0.65 ± .13) as compared to the fifth day during treatment (1.26 ±.19, p < 0.05). In saline treated rats, relative CBV gradually increased during treatment (0.89 ±.13, 1.00 ± .21, 1.13 ± .23) with no significant difference on the third day of treatment (p>0.05). In separate serial studies, microfocal X-ray CT of ex vivo brain specimens (N = 9) and immunohistochemistry for endothelial cell marker anti-CD31 (N = 8) were performed. Vascular morphology of ex vivo rat brains from micro-CT analysis showed hypervascular characteristics in tumors, and both vessel density (41.32 ± 2.34 branches/mm(3), p<0.001) and vessel tortuosity (p<0.05) were significantly reduced in tumors of rats treated with dexamethasone compared to saline (74.29 ± 3.51 branches/mm(3)). The vascular architecture of rat brain tissue was examined with anti-CD31 antibody, and dexamethasone treated tumor regions showed reduced vessel area (16.45 ± 1.36 µm(2)) as compared to saline treated tumor regions (30.83 ± 4.31 µm(2), p<0.001) and non-tumor regions (22.80 ± 1.11 µm(2), p<0.01).

CONCLUSIONS/SIGNIFICANCE: Increased vascular density and tortuosity are culprit to abnormal perfusion, which is transiently reduced during dexamethasone treatment.

Author List

Darpolor MM, Molthen RC, Schmainda KM

Author

Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Vessels
Cerebrovascular Circulation
Dexamethasone
Disease Models, Animal
Gliosarcoma
Magnetic Resonance Imaging
Perfusion
Platelet Endothelial Cell Adhesion Molecule-1
Rats
Rats, Inbred F344
Tomography, X-Ray Computed