Skip to main content
Log in

Application of localized 31P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease

  • Magnetic Resonance
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Saturation transfer (ST) phosphorus MR spectroscopy (31P MRS) enables in vivo insight into energy metabolism and thus could identify liver conditions currently diagnosed only by biopsy. This study assesses the reproducibility of the localized 31P MRS ST in liver at 7 T and tests its potential for noninvasive differentiation of non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH).

Methods

After the ethics committee approval, reproducibility of the localized 31P MRS ST at 7 T and the biological variation of acquired hepato-metabolic parameters were assessed in healthy volunteers. Subsequently, 16 suspected NAFL/NASH patients underwent MRS measurements and diagnostic liver biopsy. The Pi-to-ATP exchange parameters were compared between the groups by a Mann–Whitney U test and related to the liver fat content estimated by a single-voxel proton (1H) MRS, measured at 3 T.

Results

The mean exchange rate constant (k) in healthy volunteers was 0.31 ± 0.03 s−1 with a coefficient of variation of 9.0 %. Significantly lower exchange rates (p < 0.01) were found in NASH patients (k = 0.17 ± 0.04 s−1) when compared to healthy volunteers, and NAFL patients (k = 0.30 ± 0.05 s−1). Significant correlation was found between the k value and the liver fat content (r = 0.824, p < 0.01).

Conclusions

Our data suggest that the 31P MRS ST technique provides a tool for gaining insight into hepatic ATP metabolism and could contribute to the differentiation of NAFL and NASH.

Key Points

1D localized 31 P MRS saturation transfer in the liver is reproducible at 7 T

• NASH patients have decreased hepatic Pi-to-ATP exchange rate

• In this study, hepatic metabolic activity correlates with liver fat content

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Fischbach F, Schirmer T, Thormann M et al (2008) Quantitative proton magnetic resonance spectroscopy of the normal liver and malignant hepatic lesions at 3.0 Tesla. Eur Radiol 18(11):2549–2558

    Article  CAS  PubMed  Google Scholar 

  2. Kang BK, Yu ES, Lee SS et al (2012) Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard. Invest Radiol 47(6):368–375

    Article  CAS  PubMed  Google Scholar 

  3. Meyerhoff DJ, Karczmar GS, Weiner MW (1989) Abnormalities of the liver evaluated by P-31 MRS. Invest Radiol 24(12):980–984

    Article  CAS  PubMed  Google Scholar 

  4. Chmelik M, Povazan M, Krssak M et al (2014) In vivo 31P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience. NMR Biomed. doi:10.1002/nbm.3084

    PubMed  Google Scholar 

  5. Brown TR, Ugurbil K, Shulman RG (1977) 31P nuclear magnetic resonance measurements of ATPase kinetics in aerobic Escherichia coli cells. Proc Natl Acad Sci USA 74(12):5551–5553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Szendroedi J, Chmelik M, Schmid AI et al (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 50(4):1079–1086

    Article  CAS  PubMed  Google Scholar 

  7. Schmid AI, Szendroedi J, Chmelik M et al (2011) Liver ATP synthesis is lower and relates to insulin sensitivity in patients with type 2 diabetes. Diabetes Care 34(2):448–453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43(2 Suppl 1):S99–S112

    Article  CAS  PubMed  Google Scholar 

  9. Farrell GC, George J, dela Hall PM et al (2005) Fatty liver disease: NASH and Related disorders. Blackwell, Malden

    Google Scholar 

  10. Sanyal AJ, Campbell-Sargent C, Mirshahi F et al (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120(5):1183–1192

    Article  CAS  PubMed  Google Scholar 

  11. Trauner M, Arrese M, Wagner M (2010) Fatty liver and lipotoxicity. Biochim Biophys Acta 1801(3):299–310

    Article  CAS  PubMed  Google Scholar 

  12. Bacon BR, Farahvash MJ, Janney CG et al (1994) Nonalcoholic steatohepatitis - an expanded clinical entity. Gastroenterology 107(4):1103–1109

    CAS  PubMed  Google Scholar 

  13. Sheth SG, Gordon FD, Chopra S (1997) Nonalcoholic steatohepatitis. Ann Intern Med 126(2):137–145

    Article  CAS  PubMed  Google Scholar 

  14. Dezortova M, Taimr P, Skoch A et al (2005) Etiology and functional status of liver cirrhosis by 31P MR spectroscopy. World J Gastroenterol 11(44):6926–6931

    CAS  PubMed  Google Scholar 

  15. Schmid AI, Chmelik M, Szendroedi J et al (2008) Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experiment. NMR Biomed 21(5):437–443

    Article  CAS  PubMed  Google Scholar 

  16. Valkovič L, Chmelík M, Just Kukurová I et al (2013) Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T and 7 T: a feasibility study. Eur J Radiol 82(5):745–751

    Article  PubMed  Google Scholar 

  17. Valkovič L, Bogner W, Gajdošík M et al (2014) One-dimensional image-selected in vivo spectroscopy localized phosphorus saturation transfer at 7 T. Magn Reson Med. doi:10.1002/mrm.25058

    PubMed  Google Scholar 

  18. Brunt EM, Janney CG, Di Bisceglie AM et al (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94(9):2467–2474

    Article  CAS  PubMed  Google Scholar 

  19. Ercan-Fang N, Gannon MC, Rath VL et al (2002) Integrated effects of multiple modulators on human liver glycogen phosphorylase a. Am J Physiol Endocrinol Metab 283(1):E29–E37

    CAS  PubMed  Google Scholar 

  20. Andronesi OC, Ramadan S, Ratai EM et al (2010) Spectroscopic imaging with improved gradient modulated constant adiabaticity pulses on high-field clinical scanners. J Magn Reson 203(2):283–293

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Vanhamme L, Van Huffel S, Van Hecke P et al (1999) Time-domain quantification of series of biomedical magnetic resonance spectroscopy signals. J Magn Reson 140(1):120–130

    Article  CAS  PubMed  Google Scholar 

  22. Krssak M, Hofer H, Wrba F et al (2010) Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by 1H magnetic resonance spectroscopy. Eur J Radiol 74(3):e60–e66

    Article  PubMed  Google Scholar 

  23. Hamilton G, Yokoo T, Bydder M et al (2011) In vivo characterization of the liver fat H-1 MR spectrum. NMR Biomed 24(7):784–790

    Article  PubMed  Google Scholar 

  24. Boss A, Dokumaci AS, Buehler T et al (2013) Comprehensive spectroscopic investigation of liver metabolism – a feasibility study. In: Abstracts of the ISMRM 21st annual meeting & exhibition, Salt Lake City, 20–26 April 2013, p 4031

  25. Thoma WJ, Ugurbil K (1987) Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver. Biochim Biophys Acta 893(2):225–231

    Article  CAS  PubMed  Google Scholar 

  26. Pessayre D, Fromenty B (2005) NASH: a mitochondrial disease. J Hepatol 42(6):928–940

    Article  CAS  PubMed  Google Scholar 

  27. Starmann J, Falth M, Spindelbock W et al (2012) Gene expression profiling unravels cancer-related hepatic molecular signatures in steatohepatitis but not in steatosis. Plos One 7(10):e46584

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Ibrahim M, Singh C, Ashraf Ganie M et al (2009) NASH: the hepatic injury of metabolic syndrome: a brief update. Int J Health Sci (Qassim) 3(2):265–270

    Google Scholar 

  29. Bogner W, Chmelik M, Andronesi OC et al (2011) In vivo (31)P spectroscopy by fully Adiabatic extended image selected in vivo spectroscopy: a comparison between 3 T and 7 T. Magn Reson Med 66(4):923–930

    Article  CAS  PubMed  Google Scholar 

  30. Chmelík M, Just Kukurová I, Gruber S et al (2013) Fully adiabatic 31P 2D-CSI with reduced chemical shift displacement error at 7 T–GOIA-1D-ISIS/2D-CSI. Magn Reson Med 69(5):1233–1244

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The scientific guarantor of this publication is Assistant Professor Martin Krššák, Ph.D. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study has received funding by the Vienna Spots of Excellence des Wiener Wissenschafts-und Technologie-Fonds (WWTF) - Vienna Advanced Imaging Center (VIACLIC #FA102A0017) and the OeNB Jubilaeumsfond (grant #13629, #13834, #15455) and the Slovak Grant Agency (VEGA grant #2/0013/14 and APVV grant #0513-10). No complex statistical methods were necessary for this paper. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, experimental, performed at one institution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin Krššák.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valkovič, L., Gajdošík, M., Traussnigg, S. et al. Application of localized 31P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease. Eur Radiol 24, 1602–1609 (2014). https://doi.org/10.1007/s00330-014-3141-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-014-3141-x

Keywords

Navigation