Skip to main content
Top
Published in: Neuroradiology 3/2012

01-03-2012 | Diagnostic Neuroradiology

Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers

Authors: Rishi Awasthi, Ram K. S. Rathore, Priyanka Soni, Prativa Sahoo, Ashish Awasthi, Nuzhat Husain, Sanjay Behari, Rohit K. Singh, Chandra M. Pandey, Rakesh K. Gupta

Published in: Neuroradiology | Issue 3/2012

Login to get access

Abstract

Introduction

The purpose of the present study was to look for the possible predictors which might discriminate between high- and low-grade gliomas by pooling dynamic contrast-enhanced (DCE)-perfusion derived indices and immunohistochemical markers.

Methods

DCE-MRI was performed in 76 patients with different grades of gliomas. Perfusion indices, i.e., relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), permeability (k trans and k ep), and leakage (v e) were quantified. MMP-9-, PRL-3-, HIF-1α-, and VEGF-expressing cells were quantified from the excised tumor tissues. Discriminant function analysis using these markers was used to identify discriminatory variables using a stepwise procedure. To look for correlations between immunohistochemical parameters and DCE metrics, Pearson's correlation coefficient was also used.

Results

A discriminant function for differentiating between high- and low-grade tumors was constructed using DCE-MRI-derived rCBV, k ep, and v e. The form of the functions estimated are “D 1 = 0.642 × rCBV + 0.591 × k ep − 1.501 × v e − 1.550” and “D 2 = 1.608 × rCBV + 3.033 × k ep + 5.508 × v e − 8.784” for low- and high-grade tumors, respectively. This function classified overall 92.1% of the cases correctly (89.1% high-grade tumors and 100% low-grade tumors). In addition, VEGF expression correlated with rCBV and rCBF, whereas MMP-9 expression correlated with k ep. A significant positive correlation of HIF-1α with rCBV and VEGF expression was also found.

Conclusion

DCE-MRI may be used to differentiate between high-grade and low-grade brain tumors non-invasively, which may be helpful in appropriate treatment planning and management of these patients. The correlation of its indices with immunohistochemical markers suggests that this imaging technique is useful in tissue characterization of gliomas.
Literature
1.
go back to reference Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCrossRef Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCrossRef
2.
go back to reference Daumas-Duport C, Scheithauer B, O'Fallon J, Kelly P (1998) Grading of astrocytomas. A simple and reproducible method. Cancer 62(10):2152–2165CrossRef Daumas-Duport C, Scheithauer B, O'Fallon J, Kelly P (1998) Grading of astrocytomas. A simple and reproducible method. Cancer 62(10):2152–2165CrossRef
3.
go back to reference Kondziolka D, Lunsford LD, Martinez AJ (1993) Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low grade) astrocytoma. J Neurosurg 79(4):533–536PubMedCrossRef Kondziolka D, Lunsford LD, Martinez AJ (1993) Unreliability of contemporary neurodiagnostic imaging in evaluating suspected adult supratentorial (low grade) astrocytoma. J Neurosurg 79(4):533–536PubMedCrossRef
4.
go back to reference Petrella JR, Provenzale JM (2000) MR perfusion imaging of the brain: techniques and applications. Am J Roentgenol 175(1):207–219 Petrella JR, Provenzale JM (2000) MR perfusion imaging of the brain: techniques and applications. Am J Roentgenol 175(1):207–219
5.
go back to reference Aronen HJ, Gazit IE, Louis DN et al (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191(1):41–51PubMed Aronen HJ, Gazit IE, Louis DN et al (1994) Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 191(1):41–51PubMed
6.
go back to reference Cha S, Knopp EA, Johnson G et al (2002) Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echoplanar perfusion MR imaging. Radiology 223(1):11–29PubMedCrossRef Cha S, Knopp EA, Johnson G et al (2002) Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echoplanar perfusion MR imaging. Radiology 223(1):11–29PubMedCrossRef
7.
go back to reference Pauliah M, Saxena V, Haris M, Husain N, Rathore RK, Gupta RK (2007) Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma. Magn Reson Imaging 25(9):1292–1299PubMedCrossRef Pauliah M, Saxena V, Haris M, Husain N, Rathore RK, Gupta RK (2007) Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma. Magn Reson Imaging 25(9):1292–1299PubMedCrossRef
8.
go back to reference Singh A, Haris M, Rathore D, Purwar A et al (2007) Quantification of physiological and hemodynamic indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions. J Magn Reson Imaging 26(4):871–880PubMedCrossRef Singh A, Haris M, Rathore D, Purwar A et al (2007) Quantification of physiological and hemodynamic indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions. J Magn Reson Imaging 26(4):871–880PubMedCrossRef
9.
go back to reference Haris M, Gupta RK, Singh A et al (2008) Differentiation of infective from neoplastic brain lesions by dynamic contrast-enhanced MRI. Neuroradiology 50(6):531–540PubMedCrossRef Haris M, Gupta RK, Singh A et al (2008) Differentiation of infective from neoplastic brain lesions by dynamic contrast-enhanced MRI. Neuroradiology 50(6):531–540PubMedCrossRef
10.
go back to reference Haris M, Kumar S, Raj MK et al (2008) Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas. Radiat Med 26(3):140–150PubMedCrossRef Haris M, Kumar S, Raj MK et al (2008) Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas. Radiat Med 26(3):140–150PubMedCrossRef
11.
go back to reference Awasthi R, Verma SK, Haris M, Singh A, Behari S, Jaiswal AK (2010) Comparative evaluation of dynamic contrast-enhanced perfusion with diffusion tensor imaging metrics in assessment of corticospinal tract infiltration in malignant glioma. J Comput Assist Tomogr 34(1):82–88PubMedCrossRef Awasthi R, Verma SK, Haris M, Singh A, Behari S, Jaiswal AK (2010) Comparative evaluation of dynamic contrast-enhanced perfusion with diffusion tensor imaging metrics in assessment of corticospinal tract infiltration in malignant glioma. J Comput Assist Tomogr 34(1):82–88PubMedCrossRef
12.
go back to reference Ferrara N, Devis-Smith T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25PubMedCrossRef Ferrara N, Devis-Smith T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25PubMedCrossRef
13.
14.
go back to reference An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM (1998) Stabilization of wild-type p53 by hypoxia-inducible factor-1 alpha. Nature 392(6674):405–408PubMedCrossRef An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM (1998) Stabilization of wild-type p53 by hypoxia-inducible factor-1 alpha. Nature 392(6674):405–408PubMedCrossRef
15.
go back to reference Blagosklonny MV, An WG, Romanova LY, Trepel J, Fojo T, Neckers L (1998) p53 inhibits hypoxia-inducible factor-stimulated transcription. J Biol Chem 273(20):11995–11998PubMedCrossRef Blagosklonny MV, An WG, Romanova LY, Trepel J, Fojo T, Neckers L (1998) p53 inhibits hypoxia-inducible factor-stimulated transcription. J Biol Chem 273(20):11995–11998PubMedCrossRef
16.
go back to reference VanMeter TE, Rooprai HK, Kibble MM et al (2001) The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol 53(2):213–235PubMedCrossRef VanMeter TE, Rooprai HK, Kibble MM et al (2001) The role of matrix metalloproteinase genes in glioma invasion: co-dependent and interactive proteolysis. J Neurooncol 53(2):213–235PubMedCrossRef
17.
go back to reference Levicar N, Nuttall RK, Lah TT (2003) Proteases in brain tumour progression. Acta Neurochir Wien 145(9):825–838PubMedCrossRef Levicar N, Nuttall RK, Lah TT (2003) Proteases in brain tumour progression. Acta Neurochir Wien 145(9):825–838PubMedCrossRef
18.
go back to reference Rao JS (2003) Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 3(7):489–01PubMedCrossRef Rao JS (2003) Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 3(7):489–01PubMedCrossRef
19.
go back to reference Yong VW (2005) Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 6(12):931–944PubMedCrossRef Yong VW (2005) Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 6(12):931–944PubMedCrossRef
20.
go back to reference Forsyth PA, Wong H, Laing TD et al (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79(11–12):1828–1835PubMedCrossRef Forsyth PA, Wong H, Laing TD et al (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79(11–12):1828–1835PubMedCrossRef
21.
go back to reference Jadhav U, Chigurupati S, Lakka SS, Mohanam S (2004) Inhibition of matrix metalloproteinase-9 reduces in vitro invasion and angiogenesis in human microvascular endothelial cells. Int J Oncol 25(5):1407–1414PubMed Jadhav U, Chigurupati S, Lakka SS, Mohanam S (2004) Inhibition of matrix metalloproteinase-9 reduces in vitro invasion and angiogenesis in human microvascular endothelial cells. Int J Oncol 25(5):1407–1414PubMed
22.
go back to reference Liang F, Luo Y, Dong Y et al (2008) Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase. J Biol Chem 283(16):10339–10346PubMedCrossRef Liang F, Luo Y, Dong Y et al (2008) Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase. J Biol Chem 283(16):10339–10346PubMedCrossRef
23.
go back to reference Saha S, Bardelli A, Buckhaults P et al (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294(5545):1343–1346PubMedCrossRef Saha S, Bardelli A, Buckhaults P et al (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294(5545):1343–1346PubMedCrossRef
24.
go back to reference Wu X, Zeng H, Zhang X et al (2004) Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol 164(6):2039–2054PubMedCrossRef Wu X, Zeng H, Zhang X et al (2004) Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol 164(6):2039–2054PubMedCrossRef
25.
go back to reference Parker BS, Argani P, Cook BP et al (2004) Alterations in vascular gene expression in invasive breast carcinoma. Cancer Res 64(21):7857–7866PubMedCrossRef Parker BS, Argani P, Cook BP et al (2004) Alterations in vascular gene expression in invasive breast carcinoma. Cancer Res 64(21):7857–7866PubMedCrossRef
26.
go back to reference Kong L, Li Q, Wang L, Liu Z, Sun T (2007) The value and correlation between PRL-3 expression and matrix metalloproteinase activity and expression in human gliomas. Neuropathology 27(6):516–521PubMedCrossRef Kong L, Li Q, Wang L, Liu Z, Sun T (2007) The value and correlation between PRL-3 expression and matrix metalloproteinase activity and expression in human gliomas. Neuropathology 27(6):516–521PubMedCrossRef
27.
go back to reference Singh A, Haris M, Rathore D et al (2007) Quantification of physiological and hemodynamic indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions. J Magn Reson Imaging 26(4):871–880PubMedCrossRef Singh A, Haris M, Rathore D et al (2007) Quantification of physiological and hemodynamic indices using T(1) dynamic contrast-enhanced MRI in intracranial mass lesions. J Magn Reson Imaging 26(4):871–880PubMedCrossRef
28.
29.
go back to reference Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967PubMedCrossRef Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967PubMedCrossRef
30.
go back to reference Kassner A, Thornhill R (2011) Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Meth Mol Biol 686:229–245CrossRef Kassner A, Thornhill R (2011) Measuring the integrity of the human blood-brain barrier using magnetic resonance imaging. Meth Mol Biol 686:229–245CrossRef
31.
go back to reference Vidarsson L, Thornhill RE, Liu F, Mikulis DJ, Kassner A (2009) Quantitative permeability magnetic resonance imaging in acute ischemic stroke: how long do we need to scan? Magn Reson Imaging 27(9):1216–1222PubMedCrossRef Vidarsson L, Thornhill RE, Liu F, Mikulis DJ, Kassner A (2009) Quantitative permeability magnetic resonance imaging in acute ischemic stroke: how long do we need to scan? Magn Reson Imaging 27(9):1216–1222PubMedCrossRef
32.
go back to reference Haris M, Husain N, Singh A et al (2008) Dynamic contrast-enhanced derived cerebral blood volume correlates better with leak correction than with no correction for vascular endothelial growth factor, microvascular density, and grading of astrocytoma. J Comput Assist Tomogr 32(6):955–965PubMedCrossRef Haris M, Husain N, Singh A et al (2008) Dynamic contrast-enhanced derived cerebral blood volume correlates better with leak correction than with no correction for vascular endothelial growth factor, microvascular density, and grading of astrocytoma. J Comput Assist Tomogr 32(6):955–965PubMedCrossRef
33.
go back to reference Cher LM, Murone C, Lawrentschuk N et al (2006) Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 47(3):410–418PubMed Cher LM, Murone C, Lawrentschuk N et al (2006) Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 47(3):410–418PubMed
34.
go back to reference Alvarez JI, Teale JM (2007) Evidence for differential changes of junctional complex proteins in murine neurocysticerosis dependent upon CNS vasculature. Brain Res 1169:98–111PubMedCrossRef Alvarez JI, Teale JM (2007) Evidence for differential changes of junctional complex proteins in murine neurocysticerosis dependent upon CNS vasculature. Brain Res 1169:98–111PubMedCrossRef
35.
go back to reference Zhao Y, Xiao A, diPierro CG et al (2010) An extensive invasive intracranial human glioblastoma xenograft model: role of high level matrix metalloproteinase 9. Am J Pathol 176(6):3032–3049PubMedCrossRef Zhao Y, Xiao A, diPierro CG et al (2010) An extensive invasive intracranial human glioblastoma xenograft model: role of high level matrix metalloproteinase 9. Am J Pathol 176(6):3032–3049PubMedCrossRef
Metadata
Title
Discriminant analysis to classify glioma grading using dynamic contrast-enhanced MRI and immunohistochemical markers
Authors
Rishi Awasthi
Ram K. S. Rathore
Priyanka Soni
Prativa Sahoo
Ashish Awasthi
Nuzhat Husain
Sanjay Behari
Rohit K. Singh
Chandra M. Pandey
Rakesh K. Gupta
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Neuroradiology / Issue 3/2012
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-011-0874-y

Other articles of this Issue 3/2012

Neuroradiology 3/2012 Go to the issue