Rationale and Objectives
The purpose of this study was to correlate the status of magnetic resonance contrast enhancement with immunohistologic vascular parameters such as microvascular cellular proliferation (MVCP), microvascular density (MVD), vascular endothelial growth factor receptor-2 (VEGFR-2) expression, and World Health Organization (WHO) grade obtained from image-guided biopsy specimens. We also compared perfusion computed tomography (PCT) parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and permeability surface area-product (PS) with the presence or absence of contrast enhancement.
Materials and Methods
A total of 26 image-guided biopsy specimens in 16 patients with treatment naive gliomas were obtained from contrast-enhancing (CE) and nonenhancing (NE) regions of the glioma. Contrast enhancement status was correlated with MVD, MVCP, VEGFR-2 expression, and WHO grade obtained from the biopsy specimen as well as with the PCT parameters.
Results
Contrast enhancement showed statistically significant correlation with MVCP ( P = .003) and PS ( P = .007) when compared with various immunohistologic and perfusion vascular parameters. WHO grade of the biopsy specimen showed statistically significant correlation with contrast enhancement ( P = .002), MVCP ( P < .001), and PS values ( P = .028).
Conclusion
Contrast enhancement in gliomas is primarily from a break in blood-brain barrier as evidenced by its correlation with PS and MVCP, whereas it was not statistically correlated with CBV and MVD even though it showed a positive trend. Contrast enhancement also showed significant correlation with WHO grade suggesting a biopsy from CE region in a heterogeneous glioma probably will still yield the most aggressive part of the glioma is also shown by its association with MVCP and PS estimates.
Gliomas are usually quite heterogeneous and presence or absence of contrast enhancement may not always indicate the most aggressive part of the tumor. Previous studies have shown that approximately one-third of nonenhancing (NE) gliomas are malignant , whereas 26%–46% of the low-grade tumors may show contrast enhancement . However, despite this predicament, resection or biopsy from the contrast-enhancing (CE) part in enhancing tumors is still the norm, which leads to sampling errors. Recent literature has stressed the role of functional imaging techniques to guide the biopsy to obtain the highest grade of the tumor based on metabolic, physiologic, or hemodynamic status of the tumor ; however, use of the advanced functional imaging techniques is still limited to very few centers.
Tumor angiogenesis is the biologic process by which new capillaries are formed from preexisting vessels and is a critical process for adequate tumor tissue oxygenation and nutritional supply and also tumor invasion and metastasis . Histologic methods to evaluate angiogenesis include both quantitative and qualitative assessment of the tumor vessels, mostly based on microvascular density (MVD), total microvascular area, and microvascular cellular proliferation (MVCP) as well as vascular endothelial growth factor (VEGF) expression. MVD has been used in quantifying tumor angiogenesis and also has been found to be an important independent prognostic indicator for survival in several human cancers . Similarly, MVCP , and VEGF expression have been shown to correlate with tumor grade, aggressiveness, metastatic potential, and hence patient prognosis. These immunohistologic parameters have been shown to correlate with morphologic imaging features such as presence or absence of contrast enhancement as well as with various physiologic measures especially perfusion parameters .
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Materials and methods
Study Population
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Image-guided Biopsy
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Neuropathologic Analysis
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Perfusion CT Technique
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PCT Map Analysis
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Statistical Analysis
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Results
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CE versus VEGFR-2 Immunoreactivity
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CE versus MVCP
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CE versus MVD
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Contrast Enhancement versus PCT Parameters
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Table 1
Associations with Contrast Enhancement
Parameter CE ( n = 16) NE ( n = 10)P Value VEGFR-2, n (%) 12/16 (75%) 5/9 (55%) ∗ .164 MVCP, n (%) 9 (56%) 0 (0%) .003 MVD (vessel number) mean (SE) 138.1 (40.1) 87.7 (10.4) .550 CBV (mL/100 g) mean (SE) 2.53 (0.94) 1.25 (0.14) .157 CBF (mL/100 g/min) mean (SE) 69.8 (35.7) 33.0 (5.7) .497 MTT (seconds) mean (SE) 4.49 (0.79) 3.46 (0.68) .388 PS (mL/100 g/min) mean (SE) 3.13 (1.17) 0.44 (0.07) .007
CBF, cerebral blood flow; CBV, cerebral blood volume; CE, contrast enhancing; MTT, mean transit time; MVD, microvascular density; NE, nonenhancing; PS, permeability surface area-product; VEGFR-2, vascular endothelial growth factor receptor-2.
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Associations with Biopsy Grade
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Table 2
Associations with Biopsy Grade
Parameter Low Grade ( n = 15) High Grade ( n = 10)P Value Contrast enhancement, n (%) 6 (40%) 10 (100%) .002 VEGFR-2, n (%) 8 (53%) 8 (80%) .217 MVCP, n (%) 1 (7%) 8 (80%) <.001 MVD (vessel number) mean (SE) 77.9 (8.8) 183.9 (56.2) .171 CBV (mL/100 g) mean (SE) 1.34 (0.14) 3.20 (1.37) .131 CBF (mL/100 g/min) mean (SE) 29.0 (4.8) 98.5 (51.0) .208 MTT (seconds) mean (SE) 4.39 (0.72) 3.81 (1.08) .509 PS (mL/100 g/min) mean (SE) 0.72 (0.18) 4.31 (1.57) .028
CBF, cerebral blood flow; CBV, cerebral blood volume; CE, contrast enhancing; MTT, mean transit time; MVD, microvascular density; NE, non-enhancing; PS, permeability surface area-product; VEGFR-2, vascular endothelial growth factor receptor-2.
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WHO Grading of the Biopsy Specimen and Comparison with the Final Grade of the Tumor
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Discussion
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Limitations of the Study
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Conclusions
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