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Short-term temperature effect on the HRMAS spectra of human brain tumor biopsies and their pattern recognition analysis

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Magnetic Resonance Materials in Physics, Biology and Medicine Aims and scope Submit manuscript

Abstract

Object

To investigate the effect of temperature (0 versus 37°C) in the high-resolution magic angle spinning spectroscopy (HRMAS) pattern of human brain tumor biopsies and its influence in recognition-based tumor type prediction. This proof-of-principle study addressed the bilateral discrimination between meningioma (MM) and glioblastoma multiforme (GBM) cases.

Materials and methods

Forty-three tumor biopsy samples were collected (20 MM and 23 GBM), kept frozen and later analyzed at 0°C and 37°C by HRMAS. Post-HRMAS histopathology was used to validate the tumor type. Time-course experiments (100 min) at both temperatures were carried out to monitor HRMAS pattern changes. Principal component analysis and linear discriminant analysis were used for classifier development with a training set of 20 biopsies.

Results

Temperature-dependent, spectral pattern changes mostly affected mobile lipids and choline-containing compounds resonances and were essentially reversible. Incubation of 3 MM and 3 GBM at 37°C during 100 minutes produced irreversible pattern changes below 13% in a few resonances. Classification performance of an independent test set of 7 biopsies was 100% for the pulse-and-acquire, CPMG at echo times (TE) of 30 ms and 144 ms and Hahn Echo at TE 30 ms at 0°C and 37°C. The performance for Hahn Echo spectra at 136 ms was 83.3% at 0°C and 100% at 37°C.

Conclusion

The spectral pattern of mobile lipids changes reversibly with temperature. HRMAS demonstrated potential for automated brain tumor biopsy classification. No advantage was obtained when acquiring spectra at 37°C with respect to 0°C in most of the conditions used for the discrimination addressed.

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Abbreviations

ASCII:

American Standard Code for Information Interchange

ChCCp:

Choline-containing compounds

CPMG:

Carr-Purcell-Meiboom-Gill

GBM:

Glioblastoma multiforme

HRMAS:

High resolution magic angle spinning

LDA:

Linear discriminant analysis

LOO-CV:

Leave-one-out cross-validation

ML:

Mobile lipids

MM:

Meningothelial meningioma

PCA:

Principal component analysis

TE:

Echo time

References

  1. Martínez-Bisbal MC, Martí-Bonmatí L, Piqué J, Revert A, Ferrer P, Llácer J, Piotto M, Assemat O, Celda B (2004) 1H and 13C HRMAS spectroscopy of intact biopsy samples ex vivo and in vivo 1H MRS study of human high grade gliomas. NMR Biomed 17: 191–205

    Article  PubMed  Google Scholar 

  2. Valonen PK, Griffin JL, Lehtimäki KK, Liimatainen T, Nicholson JK, Gröhn OHJ, Kauppinen RA (2005) High-resolution magic-angle-spinning 1H NMR spectroscopy reveals different responses in choline-containing metabolites upon gene therapy-induced programmed cell death in rat brain glioma. NMR Biomed 18: 252–259

    Article  CAS  PubMed  Google Scholar 

  3. Opstad KS, Bell BA, Griffiths JR, Howe FA (2008) An investigation of human brain tumour lipids by high-resolution magic angle spinning 1H MRS and histological analysis. NMR Biomed 21: 677–685

    Article  CAS  PubMed  Google Scholar 

  4. Righi V, Mucci A, Schenetti L, Bacci A, Agati R, Leonardi M, Schiavina R, Martorana G, Liguori G, Calabrese C, Boschetti E, Bonora S, Tugnoli V (2009) Identification of mobile lipids in human cancer tissues by ex vivo diffusion edited HR-MAS MRS. Oncol Reports 22: 1493–1496

    CAS  Google Scholar 

  5. Cheng LL, Ma MJ, Becerra L, Ptak T, Tracey I, Lackner A, González RG (1997) Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc Natl Acad Sci USA 94: 6408–6413

    Article  CAS  PubMed  Google Scholar 

  6. Cheng LL, Chang IW, Louis DN, Gonzalez RG (1998) Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens. Cancer Res 58: 1825–1832

    CAS  PubMed  Google Scholar 

  7. Huhn SD, Szabo CM, Gass JH, Manzi AE (2004) Metabolic profiling of normal and hypertensive rat kidney tissues by hrMAS-NMR spectroscopy. Anal Bioanal Chem 378: 1511–1519

    Article  CAS  PubMed  Google Scholar 

  8. Mahon MM, Williams AD, Soutter WP, Cox IJ, McIndoe GA, Coutts GA, Dina R, deSouza NM (2004) 1H magnetic resonance spectroscopy of invasive cervical cancer: an in vivo study with ex vivo corroboration. NMR Biomed 17: 1–9

    Article  PubMed  Google Scholar 

  9. Barba I, Cabañas ME, Arús C (1999) The relationship between nuclear magnetic resonance-visible lipids, lipid droplets, and cell proliferation in cultured C6 cells. Cancer Res 59: 1861–1868

    CAS  PubMed  Google Scholar 

  10. Quintero MR, Cabañas ME, Arús C (2006) A possible cellular explanation for the NMR-visible mobile lipid (ML) changes in cultured C6 glioma cells with growth. Biochim Biophys Acta 1771: 31–44

    PubMed  Google Scholar 

  11. Tate AR, Foxall PJD, Holmes E, Moka D, Spraul M, Nicholson JK, Lindon JC (2000) Distinction between normal and renal cel carcinoma kidney cortical biopsy samples using pattern recognition of 1H magic angle spinning (MAS). NMR spectra NMR Biomed 13: 64–71

    Article  CAS  Google Scholar 

  12. Mahon MM, deSouza NM, Dina R, Soutter WP, McIndoe GA, Williams AD, Cox IJ (2004) Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy study. NMR Biomed 17: 144–153

    Article  PubMed  Google Scholar 

  13. Sitter B, Sonnewald U, Spraul M, Fjösne HE, Gribbestad IS (2002) High-resolution magic angle spinning MRS of breast cancer tissue. NMR Biomed 15: 327–337

    Article  CAS  PubMed  Google Scholar 

  14. Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne IS, Gribbestad HE (2006) Comparison of HR MAS MR spectroscopic profiles of breast cancer with clinical parameters. NMR Biomed 19: 30–40

    Article  CAS  PubMed  Google Scholar 

  15. Tsang TM, Griffin JL, Haselden J, Fish C, Holmes E (2005) Metabolic characterization of distinct neuroanatomical regions in rats by magic angle spinning 1H nuclear magnetic resonance spectroscopy. Magn Reson Med 53: 1018–1024

    Article  CAS  PubMed  Google Scholar 

  16. Righi V, Roda JM, Paz J, Mucci A, Tugnoli V, Rodriguez-Tarduchy G, Barrios L, Schenetti L, Cerdán S, García-Martín ML (2009) 1H HR-MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas. NMR Biomed 22(6): 629–637

    Article  CAS  PubMed  Google Scholar 

  17. Braun S, Kalinowski H, Berger S (1998) 150 and more basic NMR experiments. Wiley-VCH, Weinheim

    Google Scholar 

  18. Hahn EL (1950) Spin echoes. Phys Rev 80(4): 580

    Article  Google Scholar 

  19. Carr HY, Purcell EM (1954) Effects of diffusion on free precession in nuclear magnetic resonance experiments. Phys Rev 94(3): 630

    Article  CAS  Google Scholar 

  20. Tate AR, Griffiths JR, Martínez-Pérez I, Moreno A, Barba I, Cabañas ME, Watson D, Alonso J, Bartumeus F, Isamat F, Ferrer I, Vila F, Ferrer E, Capdevila A, Arús C (1998) Towards a method for automated classification of 1H MRS spectra from brain tumours. NMR Biomed 11: 177–191

    Article  CAS  PubMed  Google Scholar 

  21. Team RDC: (2006) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

    Google Scholar 

  22. Fukunaga K (1990) Introduction to statistical pattern recognition. Elsevier, Amsterdam

    Google Scholar 

  23. Hagberg G (1998) From magnetic resonance spectroscopy to classification of tumours. A review of pattern recognition methods. NMR Biomed 11: 148–156

    Article  CAS  PubMed  Google Scholar 

  24. Martínez-Pérez I, Moreno A, Alonso J, Aguas J, Conesa G, Capdevila A, Arús C (1997) Diagnosis of brain abcess by magnetic resonance spectroscopy. Report of two cases. J Neurosurg 86: 708–713

    Article  PubMed  Google Scholar 

  25. Moreno A, López LA, Fabra A, Arús C (1998) 1H MRS markers of tumour growth in intrasplenic tumours and liver metastasis induced by injection of HT-29 cells in nude mice spleen. NMR Biomed 11: 93–106

    Article  CAS  PubMed  Google Scholar 

  26. Valverde D, Quintero MR, Candiota AP, Badiella L, Cabañas ME, Arús C (2006) Analysis of the changes in the 1H NMR spectral pattern of percloric acid extracts of C6 cells with growth. NMR Biomed 19: 223–230

    Article  CAS  PubMed  Google Scholar 

  27. Chen JH, Enloe BM, Weybright P, Campbell N, Dorfman D, Fletcher D, Cory DG, Singer S (2002) Biochemical correlates of thiazolidinedione-induced adipocyte differentiation by high- resolution magic angle spinning. NMR spectrosc Magn Reson Med 48: 602–610

    CAS  Google Scholar 

  28. Kauppinen RA, Niskanen T, Hakumaki J, Williams SR (1993) Quantitative analysis of 1H NMR detected proteins in the rat cerebral cortex in vivo and in vitro. NMR Biomed 6: 242–247

    Article  CAS  PubMed  Google Scholar 

  29. Opstad KS, Provencher SW, Bell BA, Griffiths JR, Howe FA (2003) Detection of elevated glutathione in meningiomas by quantitative in vivo 1H MRS. Magn Reson Med 49: 632–637

    Article  CAS  PubMed  Google Scholar 

  30. Grande S, Luciani AM, Rosi A, Palma A, Giovannini C, Sapora O, Guidoni L, Viti V (2007) Metabolism of glutathione in tumour cells as evidenced by 1H MRS. FEBS Lett 581(4): 637–643

    Article  CAS  PubMed  Google Scholar 

  31. Cheng LL, Anthony DC, Comite AR, Black PM, Tzika AA, González RG (2000) Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy. Neuro Oncol 2: 87–95

    CAS  PubMed  Google Scholar 

  32. Tugnoli V, Schenetti L, Mucci A, Parenti F, Cagnoli R, Righi V, Trinchero A, Nocetti L, Toraci C, Mavilla L, Trentini G, Zunarelli E, Tosi MR (2006) Ex vivo HR-MAS MRS of human meningiomas: a comparison with in vivo 1H MR spectra. Int J Mol Med 18: 859–869

    CAS  PubMed  Google Scholar 

  33. Remy C, Fouilhe N, Barba I, Sam-Lai E, Lahrech H, Cucurella MG, Izquierdo M, Moreno A, Ziegler A, Massarelli R, Decorps M, Arús C (1997) Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic resonance correspond to lipid droplets. Cancer Res 57: 407–414

    CAS  PubMed  Google Scholar 

  34. Kuesel AC, Sutherland GR, Halliday W, Smith IC (1994) 1H MRS of high grade astrocytomas: mobile lipid accumulation in necrotic tissue. NMR Biomed 7: 149–155

    Article  CAS  PubMed  Google Scholar 

  35. Kuesel A, Donnelly S, Halliday W, Sutherland G, Smith I (1994) Mobile lipids and metabolic heterogeneity of brain tumours as detectable by ex vivo 1H MR spectroscopy. NMR Biomed 7: 172–180

    Article  CAS  PubMed  Google Scholar 

  36. Hamilton JA, Small DM, Parks JS (1983) 1H NMR studies of lymph chylomicron and very low density lipoproteins from nonhuman primates. J Biol Chem 25: 1172–1179

    Google Scholar 

  37. Parks JS, Hauser H (1996) Low density lipoprotein particle size and core cholesteryl ester physical state affect the proton NRM magnetic environment of fatty acid methylene and methyl nuclei. J Lipid Res 37: 1289–1297

    CAS  PubMed  Google Scholar 

  38. Deckelbaum RJ, Shipley GG, Small DM (1977) Structure and interactions of lipids in human plasma low density lipoproteins. J Biol Chem 25: 744–754

    Google Scholar 

  39. Arús C, Chang YC, Bárány M (1985) Proton nuclear magnetic resonance spectra of excised rat brain. Assignment of resonances. Physiol Chem Phys Med NMR 17: 23–33

    PubMed  Google Scholar 

  40. Wright A, Opstad K, Griffiths J, Howe F (2006) Quantitative total correlation spectroscopy of brain tumour tissue with high resolution magic angle spinning. NMR Magn Reson Mater Phy 19(Suppl 1): 52–53

    Google Scholar 

  41. Swanson MG, Zektzer AS, Tabatabai ZL, Simko J, Jarso S, Keshari KR, Schmitt L, Carroll PR, Shinohara K, Vigneron DB, Kurhanewicz J (2006) Quantitative analysis of prostate metabolites using 1H HR-MAS spectroscopy. Magn Reson Med 55(6): 1257–1264

    Article  CAS  PubMed  Google Scholar 

  42. Opstad KS, Bell BA, Griffiths JR, Howe FA (2008) 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 21: 1138–1147

    Article  CAS  PubMed  Google Scholar 

  43. Korshunov A, Sycheva R, Golanov A (2006) Genetically distinct and clinically relevant subtypes of glioblastoma defined by array-based comparative genomic hybridization (array-CGHI). Acta Neuropathol 111: 465–474

    Article  CAS  PubMed  Google Scholar 

  44. Liang Y, Diehn M, Watson N, Bollen AW, Aldape KD, Nicholas MK, Lamborn KR, Berger MS, Botstein D, Brown PO, Israel MA (2006) Gene expresion profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci USA 102: 5814–5819

    Article  Google Scholar 

  45. Li A, Walling J, Ahn S, Kotliarov Y, Su Q, Quezado M, Oberholtzer JC, Park J, Zenklusen JC, Fine H (2009) Unsupervised analysis of transcriptomic profiles reveals six glioma subtypes. Cancer Res 69: 2091–2099

    Article  CAS  PubMed  Google Scholar 

  46. García-Gómez JM, Tortajada S, Vidal C, Julià-Sapé M, Luts J, Moreno-Torres A, Huffel SV, Arús C, Robles M (2008) The effect of combining two echo times in automatic brain tumor classification by MRS. NMR Biomed 21(10): 1112–1125

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departament de Bioquímica i Biologia Molecular, Unitat de Biociències, Edifici C, Campus Universitat Autònoma de Barcelona, Cerdanyola del Vallès, 08193, Spain

    Daniel Valverde-Saubí, Ana Paula Candiota, Myriam Dávila & Carles Arús

  2. Servei RMN Parc Científic de Barcelona, Universitat de Barcelona, Barcelona, Spain

    Maria Antònia Molins & Miguel Feliz

  3. Servei de Neurocirurgia, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain

    Óscar Godino & Juan José Acebes

  4. Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Cerdanyola del Vallès, España

    Daniel Valverde-Saubí, Ana Paula Candiota, Óscar Godino, Myriam Dávila, Juan José Acebes & Carles Arús

Authors
  1. Daniel Valverde-Saubí
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  2. Ana Paula Candiota
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  3. Maria Antònia Molins
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  4. Miguel Feliz
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  8. Carles Arús
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Corresponding author

Correspondence to Carles Arús.

Additional information

Contract/Grant sponsor: Funding from eTUMOUR (LIFESCIHEALTH-503094), Health Agents (IST-027214), MEDIVO2 (MEC, SAF 2005-03650) and PHENOIMA (MICINN, SAF2008-03323).

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Valverde-Saubí, D., Candiota, A.P., Molins, M.A. et al. Short-term temperature effect on the HRMAS spectra of human brain tumor biopsies and their pattern recognition analysis. Magn Reson Mater Phy 23, 203–215 (2010). https://doi.org/10.1007/s10334-010-0218-7

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