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Published in: Acta Neurochirurgica 8/2012

Open Access 01-08-2012 | Clinical Article

The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas

Authors: Jun Guo, Chengjun Yao, Hong Chen, Dongxiao Zhuang, Weijun Tang, Guang Ren, Yin Wang, Jinsong Wu, Fengping Huang, Liangfu Zhou

Published in: Acta Neurochirurgica | Issue 8/2012

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Abstract

Background

The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging (1H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread.

Method

Eighteen patients with different grades of glioma were examined using 1H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated.

Results

In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG.

Conclusions

HGG and LGG exhibit different spectroscopic patterns. Using 1H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.
Literature
1.
go back to reference Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J (2010) Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 34:1199–1204PubMedCrossRef Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J (2010) Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 34:1199–1204PubMedCrossRef
2.
go back to reference Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254PubMedCrossRef Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, Ackermann U, Tessmer C, Korshunov A, Zentgraf H, Hartmann C, von Deimling A (2010) Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol 20:245–254PubMedCrossRef
3.
go back to reference Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601PubMedCrossRef Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009) Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol 118:599–601PubMedCrossRef
4.
go back to reference Chen J, Huang SL, Li T, Chen XL (2006) In vivo research in astrocytoma cell proliferation with 1H-magnetic resonance spectroscopy: correlation with histopathology and immunohistochemistry. Neuroradiology 48:312–318PubMedCrossRef Chen J, Huang SL, Li T, Chen XL (2006) In vivo research in astrocytoma cell proliferation with 1H-magnetic resonance spectroscopy: correlation with histopathology and immunohistochemistry. Neuroradiology 48:312–318PubMedCrossRef
5.
go back to reference Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM (2005) Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer 103:1227–1233PubMedCrossRef Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM (2005) Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer 103:1227–1233PubMedCrossRef
6.
go back to reference Croteau D, Scarpace L, Hearshen D, Gutierrez J, Fisher JL, Rock JP, Mikkelsen T (2001) Correlation between magnetic resonance spectroscopy imaging and image-guided biopsies: semiquantitative and qualitative histopathological analyses of patients with untreated glioma. Neurosurgery 49:823–829PubMed Croteau D, Scarpace L, Hearshen D, Gutierrez J, Fisher JL, Rock JP, Mikkelsen T (2001) Correlation between magnetic resonance spectroscopy imaging and image-guided biopsies: semiquantitative and qualitative histopathological analyses of patients with untreated glioma. Neurosurgery 49:823–829PubMed
7.
go back to reference De Stefano N, Matthews PM, Arnold DL (1995) Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 34:721–727PubMedCrossRef De Stefano N, Matthews PM, Arnold DL (1995) Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 34:721–727PubMedCrossRef
8.
go back to reference Dowling C, Bollen AW, Noworolski SM, McDermott MW, Barbaro NM, Day MR, Henry RG, Chang SM, Dillon WP, Nelson SJ, Vigneron DB (2001) Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens. AJNR Am J Neuroradiol 22:604–612PubMed Dowling C, Bollen AW, Noworolski SM, McDermott MW, Barbaro NM, Day MR, Henry RG, Chang SM, Dillon WP, Nelson SJ, Vigneron DB (2001) Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens. AJNR Am J Neuroradiol 22:604–612PubMed
9.
go back to reference Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53:799–808PubMedCrossRef Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53:799–808PubMedCrossRef
10.
go back to reference Ganslandt O, Stadlbauer A, Fahlbusch R, Kamada K, Buslei R, Blumcke I, Moser E, Nimsky C (2005) Proton magnetic resonance spectroscopic imaging integrated into image-guided surgery: correlation to standard magnetic resonance imaging and tumor cell density. Neurosurgery 56(291–298):291–298PubMedCrossRef Ganslandt O, Stadlbauer A, Fahlbusch R, Kamada K, Buslei R, Blumcke I, Moser E, Nimsky C (2005) Proton magnetic resonance spectroscopic imaging integrated into image-guided surgery: correlation to standard magnetic resonance imaging and tumor cell density. Neurosurgery 56(291–298):291–298PubMedCrossRef
11.
go back to reference Kelly PJ, Daumas-Duport C, Kispert DB, Kall BA, Scheithauer BW, Illig JJ (1987) Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg 66:865–874PubMedCrossRef Kelly PJ, Daumas-Duport C, Kispert DB, Kall BA, Scheithauer BW, Illig JJ (1987) Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms. J Neurosurg 66:865–874PubMedCrossRef
12.
go back to reference Kemp GJ (2000) Non-invasive methods for studying brain energy metabolism: what they show and what it means. Dev Neurosci 22:418–428PubMedCrossRef Kemp GJ (2000) Non-invasive methods for studying brain energy metabolism: what they show and what it means. Dev Neurosci 22:418–428PubMedCrossRef
13.
go back to reference Kimura T, Sako K, Gotoh T, Tanaka K, Tanaka T (2001) In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement. NMR Biomed 14:339–349PubMedCrossRef Kimura T, Sako K, Gotoh T, Tanaka K, Tanaka T (2001) In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like enhancement. NMR Biomed 14:339–349PubMedCrossRef
14.
go back to reference Liu X, Germin BI, Zhong J, Ekholm S (2010) N-Acetyl peak in MR spectra of intracranial metastatic mucinous adenocarcinomas. Magn Reson Imaging 28:1390–1394PubMedCrossRef Liu X, Germin BI, Zhong J, Ekholm S (2010) N-Acetyl peak in MR spectra of intracranial metastatic mucinous adenocarcinomas. Magn Reson Imaging 28:1390–1394PubMedCrossRef
15.
go back to reference Matsumura A, Isobe T, Anno I, Takano S, Kawamura H (2005) Correlation between choline and MIB-1 index in human gliomas. A quantitative in proton MR spectroscopy study J Clin Neurosci 12:416–420 Matsumura A, Isobe T, Anno I, Takano S, Kawamura H (2005) Correlation between choline and MIB-1 index in human gliomas. A quantitative in proton MR spectroscopy study J Clin Neurosci 12:416–420
16.
go back to reference McKnight TR, Lamborn KR, Love TD, Berger MS, Chang S, Dillon WP, Bollen A, Nelson SJ (2007) Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas. J Neurosurg 106:660–666PubMedCrossRef McKnight TR, Lamborn KR, Love TD, Berger MS, Chang S, Dillon WP, Bollen A, Nelson SJ (2007) Correlation of magnetic resonance spectroscopic and growth characteristics within Grades II and III gliomas. J Neurosurg 106:660–666PubMedCrossRef
17.
go back to reference McKnight TR, von Dem BM, Vigneron DB, Lu Y, Berger MS, McDermott MW, Dillon WP, Graves EE, Pirzkall A, Nelson SJ (2002) Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg 97:794–802PubMedCrossRef McKnight TR, von Dem BM, Vigneron DB, Lu Y, Berger MS, McDermott MW, Dillon WP, Graves EE, Pirzkall A, Nelson SJ (2002) Histopathological validation of a three-dimensional magnetic resonance spectroscopy index as a predictor of tumor presence. J Neurosurg 97:794–802PubMedCrossRef
18.
go back to reference Miller BL (1991) A review of chemical issues in 1 H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 4:47–52PubMedCrossRef Miller BL (1991) A review of chemical issues in 1 H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 4:47–52PubMedCrossRef
19.
go back to reference Mirbahai L, Wilson M, Shaw CS, McConville C, Malcomson RD, Griffin JL, Kauppinen RA, Peet AC (2011) 1 H magnetic resonance spectroscopy metabolites as biomarkers for cell cycle arrest and cell death in rat glioma cells. Int J Biochem Cell Biol 43:990–1001PubMedCrossRef Mirbahai L, Wilson M, Shaw CS, McConville C, Malcomson RD, Griffin JL, Kauppinen RA, Peet AC (2011) 1 H magnetic resonance spectroscopy metabolites as biomarkers for cell cycle arrest and cell death in rat glioma cells. Int J Biochem Cell Biol 43:990–1001PubMedCrossRef
20.
go back to reference Momota H, Narita Y, Matsushita Y, Miyakita Y, Shibui S (2010) p53 abnormality and tumor invasion in patients with malignant astrocytoma. Brain Tumor Pathol 27:95–101PubMedCrossRef Momota H, Narita Y, Matsushita Y, Miyakita Y, Shibui S (2010) p53 abnormality and tumor invasion in patients with malignant astrocytoma. Brain Tumor Pathol 27:95–101PubMedCrossRef
21.
go back to reference Narayana A, Chang J, Thakur S, Huang W, Karimi S, Hou B, Kowalski A, Perera G, Holodny A, Gutin PH (2007) Use of MR spectroscopy and functional imaging in the treatment planning of gliomas. Br J Radiol 80:347–354PubMedCrossRef Narayana A, Chang J, Thakur S, Huang W, Karimi S, Hou B, Kowalski A, Perera G, Holodny A, Gutin PH (2007) Use of MR spectroscopy and functional imaging in the treatment planning of gliomas. Br J Radiol 80:347–354PubMedCrossRef
22.
go back to reference Park I, Bok R, Ozawa T, Phillips JJ, James CD, Vigneron DB, Ronen SM, Nelson SJ (2011) Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13 C MR metabolic imaging. J Magn Reson Imaging 33:1284–1290PubMedCrossRef Park I, Bok R, Ozawa T, Phillips JJ, James CD, Vigneron DB, Ronen SM, Nelson SJ (2011) Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13 C MR metabolic imaging. J Magn Reson Imaging 33:1284–1290PubMedCrossRef
23.
go back to reference Pirzkall A, Li X, Oh J, Chang S, Berger MS, Larson DA, Verhey LJ, Dillon WP, Nelson SJ (2004) 3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI. Int J Radiat Oncol Biol Phys 59:126–137PubMedCrossRef Pirzkall A, Li X, Oh J, Chang S, Berger MS, Larson DA, Verhey LJ, Dillon WP, Nelson SJ (2004) 3D MRSI for resected high-grade gliomas before RT: tumor extent according to metabolic activity in relation to MRI. Int J Radiat Oncol Biol Phys 59:126–137PubMedCrossRef
24.
go back to reference Quinones-Hinojosa A, Sanai N, Smith JS, McDermott MW (2005) Techniques to assess the proliferative potential of brain tumors. J Neurooncol 74:19–30PubMedCrossRef Quinones-Hinojosa A, Sanai N, Smith JS, McDermott MW (2005) Techniques to assess the proliferative potential of brain tumors. J Neurooncol 74:19–30PubMedCrossRef
25.
go back to reference Rock JP, Hearshen D, Scarpace L, Croteau D, Gutierrez J, Fisher JL, Rosenblum ML, Mikkelsen T (2002) Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery 51:919–920 Rock JP, Hearshen D, Scarpace L, Croteau D, Gutierrez J, Fisher JL, Rosenblum ML, Mikkelsen T (2002) Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery 51:919–920
26.
go back to reference Sabatier J, Gilard V, Malet-Martino M, Ranjeva JP, Terral C, Breil S, Delisle MB, Manelfe C, Tremoulet M, Berry I (1999) Characterization of choline compounds with in vitro 1 H magnetic resonance spectroscopy for the discrimination of primary brain tumors. Invest Radiol 34:230–235PubMedCrossRef Sabatier J, Gilard V, Malet-Martino M, Ranjeva JP, Terral C, Breil S, Delisle MB, Manelfe C, Tremoulet M, Berry I (1999) Characterization of choline compounds with in vitro 1 H magnetic resonance spectroscopy for the discrimination of primary brain tumors. Invest Radiol 34:230–235PubMedCrossRef
27.
go back to reference Sankar T, Caramanos Z, Assina R, Villemure JG, Leblanc R, Langleben A, Arnold DL, Preul MC (2008) Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. J Neurooncol 90:63–76PubMedCrossRef Sankar T, Caramanos Z, Assina R, Villemure JG, Leblanc R, Langleben A, Arnold DL, Preul MC (2008) Prospective serial proton MR spectroscopic assessment of response to tamoxifen for recurrent malignant glioma. J Neurooncol 90:63–76PubMedCrossRef
28.
go back to reference Schluter M, Stieltjes B, Hahn HK, Rexilius J, Konrad-verse O, Peitgen HO (2005) Detection of tumour infiltration in axonal fibre bundles using diffusion tensor imaging. Int J Med Robot 1:80–86PubMed Schluter M, Stieltjes B, Hahn HK, Rexilius J, Konrad-verse O, Peitgen HO (2005) Detection of tumour infiltration in axonal fibre bundles using diffusion tensor imaging. Int J Med Robot 1:80–86PubMed
29.
go back to reference Shaw EG, Wisoff JH (2003) Prospective clinical trials of intracranial low-grade glioma in adults and children. Neuro Oncol 5:153–160PubMedCrossRef Shaw EG, Wisoff JH (2003) Prospective clinical trials of intracranial low-grade glioma in adults and children. Neuro Oncol 5:153–160PubMedCrossRef
30.
go back to reference Shimizu H, Kumabe T, Shirane R, Yoshimoto T (2000) Correlation between choline level measured by proton MR spectroscopy and Ki-67 labeling index in gliomas. AJNR Am J Neuroradiol 21:659–665PubMed Shimizu H, Kumabe T, Shirane R, Yoshimoto T (2000) Correlation between choline level measured by proton MR spectroscopy and Ki-67 labeling index in gliomas. AJNR Am J Neuroradiol 21:659–665PubMed
31.
go back to reference Stadlbauer A, Buchfelder M, Doelken MT, Hammen T, Ganslandt O (2011) Magnetic resonance spectroscopic imaging for visualization of the infiltration zone of glioma. Cen Eur Neurosurg 72:63–69CrossRef Stadlbauer A, Buchfelder M, Doelken MT, Hammen T, Ganslandt O (2011) Magnetic resonance spectroscopic imaging for visualization of the infiltration zone of glioma. Cen Eur Neurosurg 72:63–69CrossRef
32.
go back to reference Stadlbauer A, Moser E, Gruber S, Buslei R, Nimsky C, Fahlbusch R, Ganslandt O (2004) Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1 H-MRSI metabolites in gliomas. Neuroimage 23:454–461PubMedCrossRef Stadlbauer A, Moser E, Gruber S, Buslei R, Nimsky C, Fahlbusch R, Ganslandt O (2004) Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1 H-MRSI metabolites in gliomas. Neuroimage 23:454–461PubMedCrossRef
33.
go back to reference Stadlbauer A, Nimsky C, Buslei R, Pinker K, Gruber S, Hammen T, Buchfelder M, Ganslandt O (2007) Proton magnetic resonance spectroscopic imaging in the border zone of gliomas: correlation of metabolic and histological changes at low tumor infiltration—initial results. Invest Radiol 42:218–223PubMedCrossRef Stadlbauer A, Nimsky C, Buslei R, Pinker K, Gruber S, Hammen T, Buchfelder M, Ganslandt O (2007) Proton magnetic resonance spectroscopic imaging in the border zone of gliomas: correlation of metabolic and histological changes at low tumor infiltration—initial results. Invest Radiol 42:218–223PubMedCrossRef
34.
go back to reference Udani V, Santarelli J, Yung Y, Cheshier S, Andrews A, Kasad Z, Tse V (2005) Differential expression of angiopoietin-1 and angiopoietin-2 may enhance recruitment of bone-marrow-derived endothelial precursor cells into brain tumors. Neurol Res 27:801–806PubMedCrossRef Udani V, Santarelli J, Yung Y, Cheshier S, Andrews A, Kasad Z, Tse V (2005) Differential expression of angiopoietin-1 and angiopoietin-2 may enhance recruitment of bone-marrow-derived endothelial precursor cells into brain tumors. Neurol Res 27:801–806PubMedCrossRef
35.
go back to reference Wang S, Fang J, Zhang T, Wang B, Chen J, Li X, Zhang S, Zhang W (2011) Magnetic resonance imaging targeting of intracranial glioma xenografts by Resovist-labeled endothelial progenitor cells. J Neurooncol 105:67-75 Wang S, Fang J, Zhang T, Wang B, Chen J, Li X, Zhang S, Zhang W (2011) Magnetic resonance imaging targeting of intracranial glioma xenografts by Resovist-labeled endothelial progenitor cells. J Neurooncol 105:67-75
36.
go back to reference Widhalm G, Krssak M, Minchev G, Wohrer A, Traub-Weidinger T, Czech T, Asenbaum S, Marosi C, Knosp E, Hainfellner JA, Prayer D, Wolfsberger S (2011) Value of 1H-magnetic resonance spectroscopy chemical shift imaging for detection of anaplastic foci in diffusely infiltrating gliomas with non-significant contrast-enhancement. J Neurol Neurosurg Psychiatry 82:512–520PubMedCrossRef Widhalm G, Krssak M, Minchev G, Wohrer A, Traub-Weidinger T, Czech T, Asenbaum S, Marosi C, Knosp E, Hainfellner JA, Prayer D, Wolfsberger S (2011) Value of 1H-magnetic resonance spectroscopy chemical shift imaging for detection of anaplastic foci in diffusely infiltrating gliomas with non-significant contrast-enhancement. J Neurol Neurosurg Psychiatry 82:512–520PubMedCrossRef
37.
go back to reference Yamahara T, Numa Y, Oishi T, Kawaguchi T, Seno T, Asai A, Kawamoto K (2010) Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging. Brain Tumor Pathol 27:81–87PubMedCrossRef Yamahara T, Numa Y, Oishi T, Kawaguchi T, Seno T, Asai A, Kawamoto K (2010) Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging. Brain Tumor Pathol 27:81–87PubMedCrossRef
Metadata
Title
The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas
Authors
Jun Guo
Chengjun Yao
Hong Chen
Dongxiao Zhuang
Weijun Tang
Guang Ren
Yin Wang
Jinsong Wu
Fengping Huang
Liangfu Zhou
Publication date
01-08-2012
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 8/2012
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-012-1418-x

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