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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

Authors: Alan J. Wright, Greg A. Fellows, John R. Griffiths, M. Wilson, B. Anthony Bell, Franklyn A. Howe

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies.

Results

1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis.

Conclusions

A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.
Appendix
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Literature
1.
Howe FA, Opstad KS: 1H MR spectroscopy of brain tumours and masses. NMR Biomed. 2003, 16: 123-131. 10.1002/nbm.822CrossRefPubMed
2.
Tate AR, Underwood J, Acosta DM, Julia-Sape M, Majos C, Moreno-Torres A, Howe FA, Graaf van der M, Lefournier V, Murphy MM: Development of a decision support system for diagnosis and grading of brain tumours using in vivo magnetic resonance single voxel spectra. NMR Biomed. 2006, 19: 411-434. 10.1002/nbm.1016CrossRefPubMed
3.
Calli C, Kitis O, Yunten N, Yurtseven T, Islekel S, Akalin T: Perfusion and diffusion MR imaging in enhancing malignant cerebral tumors. Eur J Radiol. 2006, 58: 394-403. 10.1016/j.ejrad.2005.12.032CrossRefPubMed
4.
Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, Gonzalez RG: Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA. 1997, 94: 6408-6413. 10.1073/pnas.94.12.6408PubMedCentralCrossRefPubMed
5.
Cheng LL, Anthony DC, Comite AR, Black PM, Tzika AA, Gonzalez RG: Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy. Neuro Oncol. 2000, 2: 87-95. 10.1215/15228517-2-2-87PubMedCentralPubMed
6.
Cheng LL, Chang IW, Louis DN, Gonzalez RG: Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens. Cancer Res. 1998, 58: 1825-1832.PubMed
7.
Martinez-Bisbal MC, Marti-Bonmati L, Piquer J, Revert A, Ferrer P, Llacer JL, Piotto M, Assemat O, Celda B: 1H and 13C HR-MAS spectroscopy of intact biopsy samples ex vivo and in vivo 1H MRS study of human high grade gliomas. NMR Biomed. 2004, 17: 191-205. 10.1002/nbm.888CrossRefPubMed
8.
Opstad KS, Bell BA, Griffiths JR, Howe FA: Toward accurate quantification of metabolites, lipids, and macromolecules in HRMAS spectra of human brain tumor biopsies using LCModel. Magn Reson Med. 2008, 60: 1237-1242. 10.1002/mrm.21496CrossRefPubMed
9.
Tugnoli V, Schenetti L, Mucci A, Parenti F, Cagnoli R, Righi V, Trinchero A, Nocetti L, Toraci C, Mavilla L: Ex vivo HR-MAS MRS of human meningiomas: a comparison with in vivo 1H MR spectra. Int J Mol Med. 2006, 18: 859-869.PubMed
10.
Tzika AA, Cheng LL, Goumnerova L, Madsen JR, Zurakowski D, Astrakas LG, Zarifi MK, Scott RM, Anthony DC, Gonzalez RG, Black PM: Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy. J Neurosurg. 2002, 96: 1023-1031. 10.3171/jns.2002.96.6.1023CrossRefPubMed
11.
Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC: High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours. Mol Cancer. 2009, 8: 6- 10.1186/1476-4598-8-6PubMedCentralCrossRefPubMed
12.
Opstad KS, Bell BA, Griffiths JR, Howe FA: Correlation Between in vivo 1H MRS and ex vivo 1H HRMAS Metabolite Concentrations in Human Astrocytomas. ESMRMB. 2008, Valencia, Spain.
13.
Wilson M, Davies NP, Grundy RG, Peet AC: A quantitative comparison of metabolite signals as detected by in vivo MRS with ex vivo 1H HR-MAS for childhood brain tumours. NMR Biomed. 2009, 22: 213-219. 10.1002/nbm.1306CrossRefPubMed
14.
Opstad KS, Wright AJ, Bell BA, Griffiths JR, Howe FA: Correlations between in vivo (1)H MRS and ex vivo (1)H HRMAS metabolite measurements in adult human gliomas. J Magn Reson Imaging. 31: 289-297.
15.
Liu H, Fang F, Zhu H, Xia SA, Han D, Hu L, Lei H, Liu M: Metabolic changes in temporal lobe structures measured by HR-MAS NMR at early stage of electrogenic rat epilepsy. Exp Neurol. 2008, 212: 377-385. 10.1016/j.expneurol.2008.04.013CrossRefPubMed
16.
Rabeson H, Fauvelle F, Testylier G, Foquin A, Carpentier P, Dorandeu F, van Ormondt D, Graveron-Demilly D: Quantitation with QUEST of brain HRMAS-NMR signals: application to metabolic disorders in experimental epileptic seizures. Magn Reson Med. 2008, 59: 1266-1273. 10.1002/mrm.21610CrossRefPubMed
17.
Ranjan T, Abrey LE: Current management of metastatic brain disease. Neurotherapeutics. 2009, 6: 598-603. 10.1016/j.nurt.2009.04.012CrossRefPubMed
18.
19.
Govindaraju V, Young K, Maudsley AA: Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000, 13: 129-153. 10.1002/1099-1492(200005)13:3<129::AID-NBM619>3.0.CO;2-VCrossRefPubMed
20.
Provencher SW: Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993, 30: 672-679. 10.1002/mrm.1910300604CrossRefPubMed
21.
Reynolds G, Wilson M, Peet A, Arvanitis TN: An algorithm for the automated quantitation of metabolites in in vitro NMR signals. Magn Reson Med. 2006, 56: 1211-1219. 10.1002/mrm.21081CrossRefPubMed
22.
Florian CL, Preece NE, Bhakoo KK, Williams SR, Noble M: Characteristic metabolic profiles revealed by 1H NMR spectroscopy for three types of human brain and nervous system tumours. NMR Biomed. 1995, 8: 253-264. 10.1002/nbm.1940080605CrossRefPubMed
23.
Lehnhardt FG, Bock C, Rohn G, Ernestus RI, Hoehn M: Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation. NMR Biomed. 2005, 18: 371-382. 10.1002/nbm.968CrossRefPubMed
24.
Nadal L, Leray G, Desbarats C, Darcel F, Bansard JY, Bondon A, de Certaines JD: Proton and phosphorus nuclear magnetic resonance spectroscopy of human brain tumor extracts with automatic data classification: a preliminary study. Cell Mol Biol (Noisy-le-grand). 1997, 43: 659-673.
25.
Peeling J, Sutherland G: High-resolution 1H NMR spectroscopy studies of extracts of human cerebral neoplasms. Magn Reson Med. 1992, 24: 123-136. 10.1002/mrm.1910240113CrossRefPubMed
26.
Sitter B, Sonnewald U, Spraul M, Fjosne HE, Gribbestad IS: High-resolution magic angle spinning MRS of breast cancer tissue. NMR Biomed. 2002, 15: 327-337. 10.1002/nbm.775CrossRefPubMed
27.
Griffin JL, Bollard M, Nicholson JK, Bhakoo K: Spectral profiles of cultured neuronal and glial cells derived from HRMAS (1)H NMR spectroscopy. NMR Biomed. 2002, 15: 375-384. 10.1002/nbm.792CrossRefPubMed
28.
Morvan D, Demidem A, Papon J, De Latour M, Madelmont JC: Melanoma tumors acquire a new phospholipid metabolism phenotype under cystemustine as revealed by high-resolution magic angle spinning proton nuclear magnetic resonance spectroscopy of intact tumor samples. Cancer Res. 2002, 62: 1890-1897.PubMed
29.
Zektzer AS, Swanson MG, Jarso S, Nelson SJ, Vigneron DB, Kurhanewicz J: Improved signal to noise in high-resolution magic angle spinning total correlation spectroscopy studies of prostate tissues using rotor-synchronized adiabatic pulses. Magn Reson Med. 2005, 53: 41-48. 10.1002/mrm.20335CrossRefPubMed
30.
Brand A, Leibfritz D, Hamprecht B, Dringen R: Metabolism of cysteine in astroglial cells: synthesis of hypotaurine and taurine. J Neurochem. 1998, 71: 827-832.CrossRefPubMed
31.
Lehtimaki KK, Valonen PK, Griffin JL, Vaisanen TH, Grohn OH, Kettunen MI, Vepsalainen J, Yla-Herttuala S, Nicholson J, Kauppinen RA: Metabolite changes in BT4C rat gliomas undergoing ganciclovir-thymidine kinase gene therapy-induced programmed cell death as studied by 1H NMR spectroscopy in vivo, ex vivo, and in vitro. J Biol Chem. 2003, 278: 45915-45923. 10.1074/jbc.M306209200CrossRefPubMed
32.
Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2009, 37: D603-610. 10.1093/nar/gkn810PubMedCentralCrossRefPubMed
33.
Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S: HMDB: the Human Metabolome Database. Nucleic Acids Res. 2007, 35: D521-526. 10.1093/nar/gkl923PubMedCentralCrossRefPubMed
34.
Ulrich EL, Akutsu H, Doreleijers JF, Harano Y, Ioannidis YE, Lin J, Livny M, Mading S, Maziuk D, Miller Z: BioMagResBank. Nucleic Acids Res. 2008, 36: D402-408. 10.1093/nar/gkm957PubMedCentralCrossRefPubMed
35.
Tosi MR, Fini G, Tinti A, Reggiani A, Tugnoli V: Molecular characterization of human healthy and neoplastic cerebral and renal tissues by in vitro (1)H NMR spectroscopy (review). Int J Mol Med. 2002, 9: 299-310.PubMed
36.
Opstad KS, Bell BA, Griffiths JR, Howe FA: An investigation of human brain tumour lipids by high-resolution magic angle spinning 1H MRS and histological analysis. NMR Biomed. 2008, 21: 677-685. 10.1002/nbm.1239CrossRefPubMed
37.
Pfeuffer J, Tkac I, Provencher SW, Gruetter R: Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J Magn Reson. 1999, 141: 104-120. 10.1006/jmre.1999.1895CrossRefPubMed
38.
Opstad KS, Bell BA, Griffiths JR, Howe FA: An assessment of the effects of sample ischaemia and spinning time on the metabolic profile of brain tumour biopsy specimens as determined by high-resolution magic angle spinning (1)H NMR. NMR Biomed. 2008, 21: 1138-1147. 10.1002/nbm.1296CrossRefPubMed
39.
Cho YD, Choi GH, Lee SP, Kim JK: (1)H-MRS metabolic patterns for distinguishing between meningiomas and other brain tumors. Magn Reson Imaging. 2003, 21: 663-672. 10.1016/S0730-725X(03)00097-3CrossRefPubMed
40.
Yue Q, Isobe T, Shibata Y, Anno I, Kawamura H, Yamamoto Y, Takano S, Matsumura A: New observations concerning the interpretation of magnetic resonance spectroscopy of meningioma. Eur Radiol. 2008, 18: 2901-2911. 10.1007/s00330-008-1079-6CrossRefPubMed
41.
Opstad KS, Provencher SW, Bell BA, Griffiths JR, Howe FA: Detection of elevated glutathione in meningiomas by quantitative in vivo 1H MRS. Magn Reson Med. 2003, 49: 632-637. 10.1002/mrm.10416CrossRefPubMed
42.
Opstad KS, Murphy MM, Wilkins PR, Bell BA, Griffiths JR, Howe FA: Differentiation of metastases from high-grade gliomas using short echo time 1H spectroscopy. J Magn Reson Imaging. 2004, 20: 187-192. 10.1002/jmri.20093CrossRefPubMed
43.
Castillo M, Smith JK, Kwock L: Correlation of myo-inositol levels and grading of cerebral astrocytomas. AJNR Am J Neuroradiol. 2000, 21: 1645-1649.PubMed
44.
Kinoshita Y, Kajiwara H, Yokota A, Koga Y: Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study. Neurol Med Chir (Tokyo). 1993, 33: 350-359. 10.2176/nmc.33.350CrossRef
45.
Kinoshita Y, Yokota A: Absolute concentrations of metabolites in human brain tumors using in vitro proton magnetic resonance spectroscopy. NMR Biomed. 1997, 10: 2-12. 10.1002/(SICI)1099-1492(199701)10:1<2::AID-NBM442>3.0.CO;2-NCrossRefPubMed
46.
Coulon A, Lafitte F, Hoang-Xuan K, Martin-Duverneuil N, Mokhtari K, Blustajn J, Chiras J: Radiographic findings in 37 cases of primary CNS lymphoma in immunocompetent patients. Eur Radiol. 2002, 12: 329-340. 10.1007/s003300101037CrossRefPubMed
47.
Liao W, Liu Y, Wang X, Jiang X, Tang B, Fang J, Chen C, Hu Z: Differentiation of primary central nervous system lymphoma and high-grade glioma with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Acta Radiol. 2009, 50: 217-225. 10.1080/02841850802616752CrossRefPubMed
48.
Makino Y, Sakagami H, Takeda M: Induction of cell death by ascorbic acid derivatives in human renal carcinoma and glioblastoma cell lines. Anticancer Res. 1999, 19: 3125-3132.PubMed
49.
Terpstra M, Gruetter R: 1H NMR detection of vitamin C in human brain in vivo. Magn Reson Med. 2004, 51: 225-229. 10.1002/mrm.10715CrossRefPubMed
50.
Righi V, Roda JM, Paz J, Mucci A, Tugnoli V, Rodriguez-Tarduchy G, Barrios L, Schenetti L, Cerdan S, Garcia-Martin ML: 1H HR-MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas. NMR Biomed. 2009, 22: 629-637. 10.1002/nbm.1377CrossRefPubMed
51.
Usenius JP, Vainio P, Hernesniemi J, Kauppinen RA: Choline-containing compounds in human astrocytomas studied by 1H NMR spectroscopy in vivo and in vitro. J Neurochem. 1994, 63: 1538-1543.CrossRefPubMed
52.
53.
Metadata
Title
Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers
Authors
Alan J. Wright
Greg A. Fellows
John R. Griffiths
M. Wilson
B. Anthony Bell
Franklyn A. Howe
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-66

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