Faculty Collaboration Database

Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps. Neuro Oncol 2003 Oct;5(4):235-43

Date

10/21/2003

Pubmed ID

14565159

Pubmed Central ID

PMC1920679

DOI

10.1215/S1152851703000073

Scopus ID

2-s2.0-0142061088 (requires institutional sign-in at Scopus site)   61 Citations

Abstract

Depending on dose, dexamethasone has been shown to inhibit or stimulate growth of rat 9L gliosarcoma and decrease the expression of vascular endothelial growth factor (VEGF), an important mediator of tumor-associated angiogenesis. We demonstrate, by constructing relative cerebral blood volume (rCBV) maps with MRI, that dexamethasone also decreases total blood volume while increasing microvascular blood volume in Fischer rats bearing intracranial 9L gliosarcoma. Animals were inoculated with 1 x 10(5) 9L gliosarcoma tumor cells. On days 10-14 after tumor cell inoculation, animals were intra-peritoneally injected with dexamethasone (3 mg/kg) over 5 days. MRI-derived gradient echo (GE) and spin-echo (SE) rCBV maps were created to demonstrate total vasculature (GE) and microvasculature (SE). After MRI studies were performed, the rat's vasculature was perfused with a latex compound. Total vessel volume and diameters were assessed by microscopy. Dexamethasone decreased the tumor-enhancing area of postcontrast T1-weighted images (P < 0.0001) and total tumor volume(P = 0.0085). In addition, there was a greater than 50% decrease in GE rCBV (total vasculature) (P = 0.007) as well as a significant decrease in total fractional blood volume, as validated by histology (P = 0.0007). Conversely, there was an increase in SE rCBV signal (microvasculature) in animals treated with dexamethasone (P = 0.05), which was consistent with microscopy (P < 0.0001). These data demonstrate that (1) dexamethasone selectively treats tumor vasculature, suggesting a vessel-size selective effect and (2) MRI-derived rCBV is a noninvasive technique that can be used to evaluate changes in blood volume and vascular morphology.

Author List

Badruddoja MA, Krouwer HG, Rand SD, Rebro KJ, Pathak AP, 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

Angiogenesis Inhibitors
Animals
Blood Volume
Brain Neoplasms
Cell Line, Tumor
Cerebrovascular Circulation
Dexamethasone
Gliosarcoma
Magnetic Resonance Angiography
Male
Neovascularization, Pathologic
Rats
Rats, Inbred F344