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Published in: European Radiology 7/2014

01-07-2014 | Magnetic Resonance

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

Authors: Ladislav Valkovič, Martin Gajdošík, Stefan Traussnigg, Peter Wolf, Marek Chmelík, Christian Kienbacher, Wolfgang Bogner, Michael Krebs, Michael Trauner, Siegfried Trattnig, Martin Krššák

Published in: European Radiology | Issue 7/2014

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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
Literature
1.
go back to reference 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):2549–2558PubMedCrossRef 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):2549–2558PubMedCrossRef
2.
go back to reference 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):368–375PubMedCrossRef 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):368–375PubMedCrossRef
3.
go back to reference Meyerhoff DJ, Karczmar GS, Weiner MW (1989) Abnormalities of the liver evaluated by P-31 MRS. Invest Radiol 24(12):980–984PubMedCrossRef Meyerhoff DJ, Karczmar GS, Weiner MW (1989) Abnormalities of the liver evaluated by P-31 MRS. Invest Radiol 24(12):980–984PubMedCrossRef
4.
go back to reference 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 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
5.
go back to reference 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):5551–5553PubMedCentralPubMedCrossRef 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):5551–5553PubMedCentralPubMedCrossRef
6.
go back to reference Szendroedi J, Chmelik M, Schmid AI et al (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 50(4):1079–1086PubMedCrossRef Szendroedi J, Chmelik M, Schmid AI et al (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 50(4):1079–1086PubMedCrossRef
7.
go back to reference 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):448–453PubMedCentralPubMedCrossRef 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):448–453PubMedCentralPubMedCrossRef
8.
go back to reference Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43(2 Suppl 1):S99–S112PubMedCrossRef Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43(2 Suppl 1):S99–S112PubMedCrossRef
9.
go back to reference Farrell GC, George J, dela Hall PM et al (2005) Fatty liver disease: NASH and Related disorders. Blackwell, Malden Farrell GC, George J, dela Hall PM et al (2005) Fatty liver disease: NASH and Related disorders. Blackwell, Malden
10.
go back to reference Sanyal AJ, Campbell-Sargent C, Mirshahi F et al (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120(5):1183–1192PubMedCrossRef Sanyal AJ, Campbell-Sargent C, Mirshahi F et al (2001) Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 120(5):1183–1192PubMedCrossRef
11.
go back to reference Trauner M, Arrese M, Wagner M (2010) Fatty liver and lipotoxicity. Biochim Biophys Acta 1801(3):299–310PubMedCrossRef Trauner M, Arrese M, Wagner M (2010) Fatty liver and lipotoxicity. Biochim Biophys Acta 1801(3):299–310PubMedCrossRef
12.
go back to reference Bacon BR, Farahvash MJ, Janney CG et al (1994) Nonalcoholic steatohepatitis - an expanded clinical entity. Gastroenterology 107(4):1103–1109PubMed Bacon BR, Farahvash MJ, Janney CG et al (1994) Nonalcoholic steatohepatitis - an expanded clinical entity. Gastroenterology 107(4):1103–1109PubMed
13.
14.
go back to reference 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):6926–6931PubMed 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):6926–6931PubMed
15.
go back to reference 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):437–443PubMedCrossRef 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):437–443PubMedCrossRef
16.
go back to reference 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):745–751PubMedCrossRef 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):745–751PubMedCrossRef
17.
go back to reference 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 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
18.
go back to reference 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):2467–2474PubMedCrossRef 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):2467–2474PubMedCrossRef
19.
go back to reference 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–E37PubMed 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–E37PubMed
20.
go back to reference 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):283–293PubMedCentralPubMedCrossRef 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):283–293PubMedCentralPubMedCrossRef
21.
go back to reference 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):120–130PubMedCrossRef 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):120–130PubMedCrossRef
22.
go back to reference 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–e66PubMedCrossRef 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–e66PubMedCrossRef
23.
go back to reference Hamilton G, Yokoo T, Bydder M et al (2011) In vivo characterization of the liver fat H-1 MR spectrum. NMR Biomed 24(7):784–790PubMedCrossRef Hamilton G, Yokoo T, Bydder M et al (2011) In vivo characterization of the liver fat H-1 MR spectrum. NMR Biomed 24(7):784–790PubMedCrossRef
24.
go back to reference 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 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.
go back to reference Thoma WJ, Ugurbil K (1987) Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver. Biochim Biophys Acta 893(2):225–231PubMedCrossRef Thoma WJ, Ugurbil K (1987) Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver. Biochim Biophys Acta 893(2):225–231PubMedCrossRef
27.
go back to reference 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):e46584PubMedCentralPubMedCrossRef 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):e46584PubMedCentralPubMedCrossRef
28.
go back to reference 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 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
29.
go back to reference 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):923–930PubMedCrossRef 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):923–930PubMedCrossRef
30.
go back to reference 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):1233–1244PubMedCrossRef 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):1233–1244PubMedCrossRef
Metadata
Title
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
Authors
Ladislav Valkovič
Martin Gajdošík
Stefan Traussnigg
Peter Wolf
Marek Chmelík
Christian Kienbacher
Wolfgang Bogner
Michael Krebs
Michael Trauner
Siegfried Trattnig
Martin Krššák
Publication date
01-07-2014
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 7/2014
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-014-3141-x

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