Purpose
To determine whether there is a correlation between vascular endothelial growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging (MRI) and to correlate the perfusion characteristics in high- versus low-grade meningiomas.
Methods and Materials
A total of 48 (24 high-grade and 24 low-grade) meningiomas with available dynamic susceptibility–weighted MRI were retrospectively reviewed for maximum CBV and semiquantitative VEGF immunoreactivity. Correlation between normalized CBV and VEGF was made using the Spearman rank test and comparison between CBV in high- versus low-grade meningiomas was made using the Wilcoxon test.
Results
There was a significant ( P = .01) correlation between normalized maximum CBV and VEGF scores with a Spearman correlation coefficient of 0.37. In addition, there was a significant ( P < .01) difference in normalized maximum CBV ratios between high-grade meningiomas (mean 12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard deviation 5.2).
Conclusion
The data suggest that CBV accurately reflects VEGF expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially serve as a useful biomarker for meningiomas, pending prospective studies.
Introduction
Vascular endothelial growth factor (VEGF) is an endothelial cell–specific antigen and angiogenic factor that that stimulates vascular endothelial cell proliferation in meningiomas . In meningiomas, the degree of VEGF and VEGF receptor expression increases with tumor grade . In particular, VEGF expression is increased by a factor of 2 in atypical meningiomas and a factor of 10 in malignant meningiomas compared with benign meningiomas . VEGF has also been implicated in peritumoral edema formation, likely as an indirect effect of neovascularity . Furthermore, it has been suggested that VEGF expression is a predictor of tumor recurrence . Although a positive correlation between cerebral blood flow (CBV) and VEGF expression has been described in gliomas , this relationship in meningiomas has not yet been reported in the literature. The purpose of this study is to determine whether there is an association between the degree of tumor perfusion measured on dynamic susceptibility–weighted magnetic resonance imaging (MRI) and the degree of VEGF expression and whether there is a difference in CBV in low- versus high-grade meningiomas.
Methods
The pathology department database was searched for cases of surgically resected meningiomas between January 2005 and December 2010. Forty-eight intracranial meningiomas with available diagnostic quality preoperative dynamic susceptibility–weighted contrast-enhanced perfusion MRI CBV maps were included in this study. All MRIs were performed using 1.5T clinical scanners (Signa; GE Healthcare, Waukesha, WI). CBV maps were generated using the Lund University Perfusion Evaluation software, which is written in Interactive Data Language (Research Systems, Boulder, CO), by using the extended blood-brain barrier leakage correction as described by Haselhorst et al . Small (0.09 to 0.44 cm 2 ), round regions of interest (ROI) were drawn by a single blinded investigator with 3 years of experience in radiology (D.T.G.) in regions with maximum intratumoral CBV values by visual inspection ( Figs 1 and 2 ). Areas of maximum CBV were determined quantitatively in a manual fashion for each section in which the tumor was visible. Areas containing cysts, necrosis, hemorrhage, large vessels, or calcification were not included in the ROI. Large ROIs were also drawn over the contralateral hemisphere normal white matter in order to calculate normalized maximum CBV to white matter ratios. Relative cerebral blood volume was computed as a ratio between the tumor CBV and the contralateral normal-appearing cerebral white matter CBV because this measurement has been shown to yield the highest interobserver and intraobserver reproducibility .
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Results
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Discussion
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Conclusion
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References
1. Pietsch T., Valter M.M., Wolf H.K., et. al.: Expression and distribution of vascular endothelial growth factor protein in human brain tumors. Acta Neuropathol 1997; 93: pp. 109-117.
2. Barresi V.: Angiogenesis in meningiomas. Brain Tumor Pathol 2011; 28: pp. 99-106.
3. Provias J., Claffey K., delAguila L., et. al.: Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema. Neurosurgery 1997; 40: pp. 1016-1026.
4. Sakuma T., Nakagawa T., Ido K., et. al.: Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human meningiomas. J Neurooncol 2008; 88: pp. 143-155.
5. Lamszus K., Lengler U., Schmidt N.O., et. al.: Vascular endothelial growth factor, hepatocyte growth factor/scatter factor, basic fibroblast growth factor, and placenta growth factor in human meningiomas and their relation to angiogenesis and malignancy. Neurosurgery 2000; 46: pp. 938-947. discussion 947–948
6. Schmid S., Aboul-Enein F., Pfisterer W., et. al.: Vascular endothelial growth factor: the major factor for tumor neovascularization and edema formation in meningioma patients. Neurosurgery 2010; 67: pp. 1703-1708. discussion 1708
7. Yamasaki F., Yoshioka H., Hama S., et. al.: Recurrence of meningiomas. Cancer 2000; 89: pp. 1102-1110.
8. Maia A.C., Malheiros S.M., da Rocha A.J., et. al.: MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas. AJNR Am J Neuroradiol 2005; 26: pp. 777-783.
9. Haselhorst R., Kappos L., Bilecen D., et. al.: Dynamic susceptibility contrast MR imaging of plaque development in multiple sclerosis: application of an extended blood-brain barrier leakage correction. J Magn Reson Imaging 2000; 11: pp. 495-505.
10. Wetzel S.G., Cha S., Johnson G., et. al.: Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study. Radiology 2002; 224: pp. 797-803.
11. Pistolesi S., Boldrini L., Gisfredi S., et. al.: Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study. Neuropathol Appl Neurobiol 2004; 30: pp. 118-125.
12. Norden A.D., Drappatz J., Wen P.Y.: Targeted drug therapy for meningiomas. Neurosurg Focus 2007; 23: pp. E12.
13. Wen P.Y., Quant E., Drappatz J., et. al.: Medical therapies for meningiomas. J Neurooncol 2010; 99: pp. 365-378.
14. Yazaki T., Takamiya Y., Costello P.C., et. al.: Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470. J Neurooncol 1995; 23: pp. 23-29.
15. Perry A., Gutmann D.H., Reifenberger G.: Molecular pathogenesis of meningiomas. J Neurooncol 2004; 70: pp. 183-202.
16. Louis D.N.Ohgaki H.Wiestler O.D. et. al.WHO Classification of Tumours of the Central Nervous System.2007.IARC PressLyon, France:
17. Folkman J.: Angiogenesis. Annu Rev Med 2006; 57: pp. 1-18.
18. Norden A.D., Drappatz J., Wen P.Y.: Novel anti-angiogenic therapies for malignant gliomas. Lancet Neurol 2008; 7: pp. 1152-1160.
19. Ragel B.T., Jensen R.L., Gillespie D.L., et. al.: Celecoxib inhibits meningioma tumor growth in a mouse xenograft model. Cancer 2007; 109: pp. 588-597.
20. Pien H.H., Fischman A.J., Thrall J.H., et. al.: Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today 2005; 10: pp. 259-266.
21. Law M., Young R.J., Babb J.S., et. al.: Gliomas: predicting time to progression or survival with cerebral blood volume measurements at dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 2008; 247: pp. 490-498.
22. Yang S., Law M., Zagzag D., et. al.: Dynamic contrast-enhanced perfusion MR imaging measurements of endothelial permeability: differentiation between atypical and typical meningiomas. AJNR Am J Neuroradiol 2003; 24: pp. 1554-1559.
23. Ginat D.T., Mangla R., Yeaney G., et. al.: Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas. AJR Am J Roentgenol 2010; 195: pp. 1391-1395.
24. Zhang H., Rödiger L.A., Shen T., et. al.: Perfusion MR imaging for differentiation of benign and malignant meningiomas. Neuroradiology 2008; 50: pp. 525-530.
25. Maiuri F., De Caro M.B., Esposito F., et. al.: Recurrences of meningiomas: predictive value of pathological features and hormonal and growth factors. J Neurooncol 2007; 82: pp. 63-68.