Skip to main content
SpringerLink
Log in

Quantification of diagnostic biomarkers to detect multiple sclerosis lesions employing 1H-MRSI at 3T

  • Scientific Paper
  • Published:
Australasian Physical & Engineering Sciences in Medicine Aims and scope Submit manuscript

Abstract

Proton magnetic resonance spectroscopic imaging (1H-MRSI) enables the quantification of metabolite concentration ratios in the brain. The major purpose of the current work is to characterize NAA/Cho, NAA/Cr and Myo/Cr in multiple sclerosis (MS) patients, and to estimate their reproducibility in healthy controls. Twelve MS patients and five healthy volunteers were imaged using 1H-MRSI at 3T. Eddy current correction was performed using a single-voxel non-water suppressed acquisition on an external water phantom. Time-domain quantification was carried out using subtract-QUEST technique, and based on an optimal simulated metabolite database. Reproducibility was evaluated on the same quantified ratios in five normal subjects. An optimal database was created for the quantification of the MRSI data, consisting of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), lactate (Lac), lipids, myo-inositol (Myo) and glutamine + glutamate (Glx). Decreasing of NAA/Cr and NAA/Cho ratios, as well as an increase in Myo/Cr ratio were observed for MS patients in comparison with control group. Reproducibility of NAA/Cr, NAA/Cho and Myo/Cr in control group was 0.98, 0.87 and 0.64, respectively, expressed as the squared correlation coefficient R 2 between duplicate experiments. We showed that MRSI alongside the time-domain quantification of spectral ratios offers a sensitive and reproducible framework to differentiate MS patients from normals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

MRS:

Magnetic resonance spectroscopy

MRSI:

Magnetic resonance spectroscopic imaging

NAA/Cr:

N-Acetyl aspartate to creatine ratio

NAA/Cho:

N-Acetyl aspartate to choline

Myo/Cr:

Myo-inositol to creatine ratio

1H-MRSI:

Proton magnetic resonance spectroscopic imaging

QUEST:

Quantitation based on quantum estimation

ECC:

Eddy current compensation

SNR:

Signal-to-noise ratio

References

  1. Simone I, Tortorella C, Federico F, Liguori M, Lucivero V, Giannini P, Carrara D, Bellacosa A, Livrea P (2001) Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and H-magnetic resonance spectroscopy study. J Neurol Sci 182(2):143–150

    Article  PubMed  CAS  Google Scholar 

  2. Aboul-Enein F, Krššák M, Höftberger R, Prayer D, Kristoferitsch W (2010) Reduced NAA-levels in the NAWM of patients with MS is a feature of progression. A study with quantitative magnetic resonance spectroscopy at 3 Tesla. PLoS One 5(7):e11625

    Article  PubMed  PubMed Central  Google Scholar 

  3. Suhy J, Rooney W, Goodkin D, Capizzano A, Soher B, Maudsley A, Waubant E, Andersson P, Weiner M (2000) 1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS. Mult Scler 6(3):148–155

    PubMed  CAS  PubMed Central  Google Scholar 

  4. Chard D, Griffin C, McLean M, Kapeller P, Kapoor R, Thompson A, Miller D (2002) Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing–remitting multiple sclerosis. Brain 125(10):2342–2352

    Article  PubMed  CAS  Google Scholar 

  5. Duarte J, Lei H, Mlynárik V, Gruetter R (2012) The neurochemical profile quantified by in vivo 1H NMR spectroscopy. Neuroimage 61(2):342–362

    Article  PubMed  CAS  Google Scholar 

  6. Rahimian N, Rad HS, Firouznia K, Ebrahimzadeh SA, Meysamie A, Vafaiean H, Harirchian MH (2013) Magnetic resonance spectroscopic findings of chronic lesions in two subtypes of multiple sclerosis: primary progressive versus relapsing remitting. Iran J Radiol 10(3):128

    Article  PubMed  PubMed Central  Google Scholar 

  7. Poullet J-B, Sima DM, Van Huffel S (2008) MRS signal quantitation: a review of time-and frequency-domain methods. J Magn Reson 195(2):134–144

    Article  PubMed  CAS  Google Scholar 

  8. Helms G, Stawiarz L, Kivisäkk P, Link H (2000) Regression analysis of metabolite concentrations estimated from localized proton MR spectra of active and chronic multiple sclerosis lesions. Magn Reson Med 43(1):102–110

    Article  PubMed  CAS  Google Scholar 

  9. Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: absolute quantification of metabolites1. Radiology 240(2):318–332

    Article  PubMed  Google Scholar 

  10. Mandal PK (2012) In vivo proton magnetic resonance spectroscopic signal processing for the absolute quantitation of brain metabolites. Eur J Radiol 81(4):e653–e664

    Article  PubMed  Google Scholar 

  11. Ratiney H, Sdika M, Coenradie Y, Cavassila S, Dv Ormondt, Graveron-Demilly D (2005) Time-domain semi-parametric estimation based on a metabolite basis set. NMR Biomed 18(1):1–13

    Article  PubMed  CAS  Google Scholar 

  12. Barker PB (2009) Clinical MR spectroscopy CB2 8RU. Cambridge University Press, UK

    Book  Google Scholar 

  13. Helms G (2008) The principles of quantification applied to in vivo proton MR spectroscopy. Eur J Radiol 67(2):218–229

    Article  PubMed  Google Scholar 

  14. Jiru F (2008) Introduction to post-processing techniques. Eur J Radiol 67(2):202–217

    Article  PubMed  Google Scholar 

  15. Wishart DS (2008) Quantitative metabolomics using NMR. TrAC Trends Anal Chem 27(3):228–237

    Article  CAS  Google Scholar 

  16. Osorio-Garcia MI, Sava ARC, Sima DM, Nielsen FU, Himmelreich U, Van Huffel S (2011) Quantification improvements of 1H MRS signals. http://cdn.intechopen.com

  17. Vafaeyan H, Rahimian N, Madadi A, Harirchian MH, Saligheh Rad H (2013) Accurate quantification of in-vivo 1H-MRSI for multiple sclerosis at 3T; reproducibility study. In: Proceedings of the 30th scientific meeting, European Society for Magnetic Resonance in Medicine and Biology, Toulouse, p 645

  18. Howe F, Barton S, Cudlip S, Stubbs M, Saunders D, Murphy M, Wilkins P, Opstad K, Doyle V, McLean M (2003) Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 49(2):223–232

    Article  PubMed  CAS  Google Scholar 

  19. Opstad KS, Griffiths JR, Bell BA, Howe FA (2008) Apparent T2 relaxation times of lipid and macromolecules: a study of high-grade tumor spectra. J Magn Reson Imaging 27:178–184

    Article  PubMed  Google Scholar 

  20. Bagory M, Durand-Dubief F, Ibarrola D, Confavreux C, Sappey-Marinier (2007) Absolute quantification in magnetic resonance spectroscopy: validation of a clinical protocol in multiple sclerosis. In: Proceedings of 29th annual international conference of the IEEE EMBS, Lyon, FrP2B3.7

  21. Bonneville F, Moriarty DM, Li BS, Babb JS, Grossman RI, Gonen O (2002) Whole-brain N-acetylaspartate concentration: correlation with T2-weighted lesion volume and expanded disability status scale score in cases of relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 23(3):371–375

    PubMed  Google Scholar 

  22. Tartaglia M, Narayanan S, De Stefano N, Arnaoutelis R, Antel S, Francis S, Santos A, Lapierre Y, Arnold D (2002) Choline is increased in pre-lesional normal appearing white matter in multiple sclerosis. J Neurol 249(10):1382–1390

    Article  PubMed  CAS  Google Scholar 

  23. Hossam M. Abd EI-Rahman, Doaa I. Hasan, Heba A. Selim, Sbah M. Lotfi, Wael M. Elsayed (2012) Clinical use of 1H MR spectroscopy in assessment of relapsing remitting and secondary progressive multiple sclerosis. Egypt Soc Radiol Nucl 43:257–264

  24. Keevil S, Barbiroli B, Brooks J, Cady E, Canese R, Carlier P, Collins D, Gilligan P, Gobbi G, Hennig J (1998) Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain. Magn Reson Imaging 16(9):1093–1106

    Article  PubMed  CAS  Google Scholar 

  25. Madadi A, Mohseni M, Fathi Kazeroni A, Karimi Alavijeh S, Saligheh Rad H (2013) Acurate quantification of metabolites ratios in glial brain tumors employing 1H-MRSI at 3T. In: Proceedings of the 30th scientific meeting, European Society for Magnetic Resonance in Medicine and Biology, Toulouse, p 644

  26. Kreis R (2015) The trouble with quality filtering based on relative Cramér-Rao lower bounds. Magn Reson Med. doi:10.1002/mrm.25568

    Google Scholar 

  27. Mandal PK, Tripathi M, Sugunan S (2012) Brain oxidative stress: detection and mapping of anti-oxidant marker ‘Glutathione’in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy. Biochem Biophys Res Commun 417(1):43–48

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This is a joint work between Quantitative MR Imaging and Spectroscopy group and Iranian Center of Neurological Research.

Author information

Authors and Affiliations

  1. Quantitative MR Imaging and Spectroscopy Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    H. Vafaeyan, S. Karimi Alavijeh, A. Madadi & H. Saligheh Rad

  2. School of Para-Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran

    H. Vafaeyan & F. Faeghi

  3. Department of Radiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    S. A. Ebrahimzadeh

  4. Iranian Center of Neurological Research, TUMS, Tehran, Iran

    N. Rahimian & M. H. Harirchian

  5. Medical Physics and Biomedical Engineering Department, TUMS, Keshavarz Boulevard, Tehran, Iran

    S. Karimi Alavijeh & H. Saligheh Rad

Authors
  1. H. Vafaeyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. A. Ebrahimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Rahimian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Karimi Alavijeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Madadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Faeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. H. Harirchian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Saligheh Rad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Saligheh Rad.

Ethics declarations

Patient Consent

Study approval was obtained from the Medical Ethics Committee of Tehran University of Medical Sciences, and patients were included if they provided written informed consent. For the data from normal subjects, all the volunteers filled out their informed consent regarding the image acquisition.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vafaeyan, H., Ebrahimzadeh, S.A., Rahimian, N. et al. Quantification of diagnostic biomarkers to detect multiple sclerosis lesions employing 1H-MRSI at 3T. Australas Phys Eng Sci Med 38, 611–618 (2015). https://doi.org/10.1007/s13246-015-0390-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13246-015-0390-1

Keywords

Search

Navigation