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Research ArticleBrain

In Vivo Correlation of Tumor Blood Volume and Permeability with Histologic and Molecular Angiogenic Markers in Gliomas

R. Jain, J. Gutierrez, J. Narang, L. Scarpace, L.R. Schultz, N. Lemke, S.C. Patel, T. Mikkelsen and J.P. Rock
American Journal of Neuroradiology February 2011, 32 (2) 388-394; DOI: https://doi.org/10.3174/ajnr.A2280
R. Jain
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J. Gutierrez
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J. Narang
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L. Scarpace
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L.R. Schultz
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N. Lemke
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S.C. Patel
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T. Mikkelsen
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J.P. Rock
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Abstract

BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo correlation of perfusion imaging parameters with angiogenic markers can help in better understanding the role of perfusion imaging as an imaging biomarker. The purpose of this study was to correlate PCT parameters such as CBV and PS with histologic and molecular angiogenic markers in gliomas.

MATERIALS AND METHODS: Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression, tumor cellularity, and WHO grade of the image-guided biopsy specimens with the PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34, and VEGFR-2 and examined under a light microscope. These histologic and molecular angiogenic markers were correlated with perfusion parameters of the region of interest corresponding to the biopsy specimen. Pearson correlation coefficients and multiple regression analyses by using clustering methods were performed to assess these correlations.

RESULTS: CBV showed a significant positive correlation with MVD (r = 0.596, P < .001), whereas PS showed a significant positive correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade. VEGFR-2 positive specimens showed higher PS and CBV; however, neither was statistically significant at the .05 level.

CONCLUSIONS: CBV showed a significant positive correlation with MVD, whereas PS showed a significant positive correlation with MVCP, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels; hence, in vivo evaluation of these could be important in a better understanding of tumor angiogenesis.

Abbreviations

CBF
cerebral blood flow
CBV
cerebral blood volume
Flk-1
fetal liver kinase-1
Flk-2
fetal liver kinase-2
HIPAA
Health Insurance Portability and Accountability Act
Ktrans
volume transfer coefficient
MVCP
microvascular cellular proliferation
MVD
microvascular density
MTT
mean transit time
PCT
perfusion CT
PS
permeability surface area product
rCBV
relative CBV
SE
standard error
TVA
total microvascular area
VEGF
vascular endothelial growth factor
VEGFR-2
vascular endothelial growth factor receptor-2
WHO
World Health Organization
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American Journal of Neuroradiology: 32 (2)
American Journal of Neuroradiology
Vol. 32, Issue 2
1 Feb 2011
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Cite this article
R. Jain, J. Gutierrez, J. Narang, L. Scarpace, L.R. Schultz, N. Lemke, S.C. Patel, T. Mikkelsen, J.P. Rock
In Vivo Correlation of Tumor Blood Volume and Permeability with Histologic and Molecular Angiogenic Markers in Gliomas
American Journal of Neuroradiology Feb 2011, 32 (2) 388-394; DOI: 10.3174/ajnr.A2280

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In Vivo Correlation of Tumor Blood Volume and Permeability with Histologic and Molecular Angiogenic Markers in Gliomas
R. Jain, J. Gutierrez, J. Narang, L. Scarpace, L.R. Schultz, N. Lemke, S.C. Patel, T. Mikkelsen, J.P. Rock
American Journal of Neuroradiology Feb 2011, 32 (2) 388-394; DOI: 10.3174/ajnr.A2280
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