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

Mohammad Haris, Nuzhat Husain, Anup Singh, Rishi Awasthi, Ram Kishore Singh Rathore, Mazhar Husain, Rakesh K. Gupta

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)588-597
Number of pages10
JournalJournal of Magnetic Resonance Imaging
Volume28
Issue number3
DOIs
Publication statusPublished - Sep 2008
Externally publishedYes

Fingerprint

Tuberculoma
Matrix Metalloproteinase 9
Vascular Endothelial Growth Factor A
Biomarkers
Microvessels
Brain
Blood-Brain Barrier
Perfusion
Cerebral Blood Volume

Keywords

  • Blood brain barrier
  • Brain tuberculoma
  • DCE-MRI
  • Matrix metalloproteinase
  • Permeability

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Dynamic contrast-enhanced (DCE) derived transfer coefficient (k trans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas. / Haris, Mohammad; Husain, Nuzhat; Singh, Anup; Awasthi, Rishi; Rathore, Ram Kishore Singh; Husain, Mazhar; Gupta, Rakesh K.

In: Journal of Magnetic Resonance Imaging, Vol. 28, No. 3, 09.2008, p. 588-597.

Research output: Contribution to journalArticle

Haris, Mohammad ; Husain, Nuzhat ; Singh, Anup ; Awasthi, Rishi ; Rathore, Ram Kishore Singh ; Husain, Mazhar ; Gupta, Rakesh K. / Dynamic contrast-enhanced (DCE) derived transfer coefficient (k trans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas. In: Journal of Magnetic Resonance Imaging. 2008 ; Vol. 28, No. 3. pp. 588-597.
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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.",
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T1 - Dynamic contrast-enhanced (DCE) derived transfer coefficient (k trans) is a surrogate marker of matrix metalloproteinase 9 (MMP-9) expression in brain tuberculomas

AU - Haris, Mohammad

AU - Husain, Nuzhat

AU - Singh, Anup

AU - Awasthi, Rishi

AU - Rathore, Ram Kishore Singh

AU - Husain, Mazhar

AU - Gupta, Rakesh K.

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - Blood brain barrier

KW - Brain tuberculoma

KW - DCE-MRI

KW - Matrix metalloproteinase

KW - Permeability

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