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


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).


CONCLUSIONS
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.
Haris
Mohammad
M
Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Husain
Nuzhat
N
Singh
Anup
A
Awasthi
Rishi
R
Singh Rathore
Ram Kishore
RK
Husain
Mazhar
M
Gupta
Rakesh K
RK
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003287:Contrast Media; D004660:Encephalitis / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016862:Tuberculoma, Intracranial / Q000175:diagnosis* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D055815:Young Adult
D015415:Biomarkers; D003287:Contrast Media; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9; D019786:Gadolinium DTPA