Dynamic contrast-enhanced (DCE) derived transfer coefficient (k trans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas

Abstract

Purpose: To correlate dynamic contrast-enhanced (DCE) MRI derived perfusion Indices with immunohistochemically obtained vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in a cellular fraction of brain tuberculomas (BT). Materials and Methods: Thirteen BT patients underwent DCE MRI. Perfusion indices (cerebral blood volume [CBV], transfer coefficient |ktrans] and leakage [ve]) maps were generated for the quantitative analysis. The CBV was corrected for the leaky blood-brain barrier (BBB). The relative CBV (rCBV), ktrans, and ve were calculated by placing 10 regions of interest (ROIs) showing the highest values in the lesion. The percentage area of VEGF and percentage area of MMP-9 and microvessel density (MVD) were quantified from 10 fields per lesion with maximal expression of the excised BT. Pearson correlation analysis between physiological indices and quantitative VEGF, MMP-9, and MVD was performed for each ROI. Results: The average value of rCBV, ktrans, ve, VEGF, MMP-9, and MVD were 3.53 ± 0.37, 2.04 ± 0.40 min -1, 0.71 ± 0.09, 12.51 ± 2.56, 18.09 ± 2.06, 10.87 ± 1.99, respectively. The ktrans (r = 0.918, P < 0.001) and ve (r = 0.899, P < 0.001) showed significant correlation with MMP-9, while rCBV correlated significantly with MVD (r = 0.962, P < 0.001) and VEGF (r = 0.868, P < 0.001). Conclusion: We conclude that the expression of MMP-9, a marker of BBB disruption and disease activity in BT correlates with DCE-derived ktrans and thus has the potential to be used as its surrogate marker. © 2008 Wiley-Liss, Inc.