Dynamic contrast-enhanced (DCE) derived transfer coefficient (ktrans) is a surrogate marker of matrix
Mohammad Haris1, Nuzhat Husain, Anup Singh
1Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
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.
Insights
Dynamic contrast-enhanced MRI perfusion indices correlate with key markers in brain tuberculomas. Matrix metalloproteinase-9 (MMP-9) expression in brain tuberculomas (BT) correlates with DCE-MRI ktrans, suggesting MMP-9 as a potential surrogate marker.
Area of Science:
- Neuroimaging and Radiology
- Oncology
- Immunohistochemistry
Background:
- Brain tuberculomas (BT) are a significant cause of morbidity.
- Accurate assessment of BT vascularity and disease activity is crucial for effective treatment.
- Dynamic contrast-enhanced (DCE) MRI offers quantitative insights into tissue perfusion.
Purpose of the Study:
- To correlate dynamic contrast-enhanced (DCE) MRI perfusion indices with immunohistochemically determined vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in brain tuberculomas (BT).
- To investigate the potential of MMP-9 as a surrogate marker for DCE-MRI derived ktrans in BT.
Main Methods:
- Thirteen BT patients underwent DCE MRI scans.
- Perfusion indices including relative cerebral blood volume (rCBV), transfer coefficient (ktrans), and leakage (ve) were calculated.
- Immunohistochemical analysis quantified VEGF, MMP-9 expression, and microvessel density (MVD) in BT tissue.
Main Results:
- Significant correlations were found between ktrans and MMP-9 (r=0.918, P<0.001), and ve and MMP-9 (r=0.899, P<0.001).
- rCBV showed significant correlation with MVD (r=0.962, P<0.001) and VEGF (r=0.868, P<0.001).
- These findings highlight the relationship between vascular markers and DCE-MRI parameters in BT.
Conclusions:
- Matrix metalloproteinase-9 (MMP-9) expression in BT correlates with DCE-MRI derived ktrans.
- MMP-9 shows potential as a non-invasive surrogate marker for BBB disruption and disease activity in BT.
- DCE-MRI derived indices provide valuable information on the pathophysiology of brain tuberculomas.


