Skip to main content
Top
Published in: European Radiology 1/2005

01-01-2005 | Hepatobiliary-Pancreas

Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease

Authors: Bengt Norén, Peter Lundberg, Marcus Ressner, Staffan Wirell, Sven Almer, Örjan Smedby

Published in: European Radiology | Issue 1/2005

Login to get access

Abstract

Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.
Literature
1.
go back to reference Graham RA, Taylor AH, Brown TR (1994) A method for calculating the distribution of pH in tissues and a new source of pH error from the 31P-NMR spectrum. Am J Physiol 266:R638–R645PubMed Graham RA, Taylor AH, Brown TR (1994) A method for calculating the distribution of pH in tissues and a new source of pH error from the 31P-NMR spectrum. Am J Physiol 266:R638–R645PubMed
2.
go back to reference Lundberg P, Harmsen E, Ho C, Vogel HJ (1990) Nuclear magnetic resonance studies of cellular metabolism. Anal Biochem 191:193–222PubMed Lundberg P, Harmsen E, Ho C, Vogel HJ (1990) Nuclear magnetic resonance studies of cellular metabolism. Anal Biochem 191:193–222PubMed
3.
go back to reference Buchli R, Duc CO, Martin E, Boesiger P (1994) Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part I. Cerebrum, cerebellum, cerebral gray and white matter. Magn Reson Med 32:447–452PubMed Buchli R, Duc CO, Martin E, Boesiger P (1994) Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part I. Cerebrum, cerebellum, cerebral gray and white matter. Magn Reson Med 32:447–452PubMed
4.
go back to reference Meyerhoff DJ, Boska MD, Thomas AM, Weiner MW (1989) Alcoholic liver disease: quantitative image-guided P-31 MR spectroscopy. Radiology 173:393–400PubMed Meyerhoff DJ, Boska MD, Thomas AM, Weiner MW (1989) Alcoholic liver disease: quantitative image-guided P-31 MR spectroscopy. Radiology 173:393–400PubMed
5.
go back to reference Rajanayagam V, Lee RR, Ackerman Z, Bradley WG, Ross BD (1992) Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis. J Magn Reson Imaging 2:183–190PubMed Rajanayagam V, Lee RR, Ackerman Z, Bradley WG, Ross BD (1992) Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis. J Magn Reson Imaging 2:183–190PubMed
6.
go back to reference Oberhaensli R, Rajagopalan B, Galloway GJ, Taylor DJ, Radda GK (1990) Study of human liver disease with P-31 magnetic resonance spectroscopy. Gut 31:463–467PubMed Oberhaensli R, Rajagopalan B, Galloway GJ, Taylor DJ, Radda GK (1990) Study of human liver disease with P-31 magnetic resonance spectroscopy. Gut 31:463–467PubMed
7.
go back to reference Li CW, Negendank WG, Murphy-Boesch J, Padavic-Shaller K, Brown TR (1996) Molar quantitation of hepatic metabolites in vivo in proton-decoupled, nuclear Overhauser effect enhanced 31P NMR spectra localized by three-dimensional chemical shift imaging. NMR Biomed 9:141–155CrossRefPubMed Li CW, Negendank WG, Murphy-Boesch J, Padavic-Shaller K, Brown TR (1996) Molar quantitation of hepatic metabolites in vivo in proton-decoupled, nuclear Overhauser effect enhanced 31P NMR spectra localized by three-dimensional chemical shift imaging. NMR Biomed 9:141–155CrossRefPubMed
8.
go back to reference Sijens PE, Dagnelie PC, Halfwerk S, van Dijk P, Wicklow K, Oudkerk M (1998) Understanding the discrepancies between 31P MR spectroscopy assessed liver metabolite concentrations from different institutions. Magn Reson Imaging 16:205–211CrossRefPubMed Sijens PE, Dagnelie PC, Halfwerk S, van Dijk P, Wicklow K, Oudkerk M (1998) Understanding the discrepancies between 31P MR spectroscopy assessed liver metabolite concentrations from different institutions. Magn Reson Imaging 16:205–211CrossRefPubMed
9.
go back to reference Tosner Z, Dezortova M, Tintera J, Hajek M (2001) Application of two-dimensional CSI for absolute quantification of phosphorus metabolites in the human liver. Magma 13:40–46CrossRefPubMed Tosner Z, Dezortova M, Tintera J, Hajek M (2001) Application of two-dimensional CSI for absolute quantification of phosphorus metabolites in the human liver. Magma 13:40–46CrossRefPubMed
10.
go back to reference Bottomley PA, Foster TB, Darrow RD (1984) Depth-resolved surface-coil spectroscopy (DRESS) for in vivo 1H, 31P, and 13C NMR. J Magn Reson 59:338–342 Bottomley PA, Foster TB, Darrow RD (1984) Depth-resolved surface-coil spectroscopy (DRESS) for in vivo 1H, 31P, and 13C NMR. J Magn Reson 59:338–342
11.
go back to reference van den Boogaart A, Van Hecke P, Van Huffel S, Graveron-Demilly D, van Ormondt D, de Beer R (1996) MRUI: a graphical user interface for accurate routine MRS data analysis. In: Proceedings of the ESMRMB 13th Annual Meeting, Prague 318 van den Boogaart A, Van Hecke P, Van Huffel S, Graveron-Demilly D, van Ormondt D, de Beer R (1996) MRUI: a graphical user interface for accurate routine MRS data analysis. In: Proceedings of the ESMRMB 13th Annual Meeting, Prague 318
12.
go back to reference van den Boogaart (1997) A MRUI MANUAL V. 96.3. A user’s guide to the Magnetic Resonance User Interface Software Package. Delft Technical University, Delft van den Boogaart (1997) A MRUI MANUAL V. 96.3. A user’s guide to the Magnetic Resonance User Interface Software Package. Delft Technical University, Delft
13.
go back to reference van der Veen JWC, de Beer R, Luyten PR, van Ormondt D (1988) Accurate quantification of in vivo 31-P NMR signals using the variable projection method and prior knowledge. Magn Reson Med 6:92–98PubMed van der Veen JWC, de Beer R, Luyten PR, van Ormondt D (1988) Accurate quantification of in vivo 31-P NMR signals using the variable projection method and prior knowledge. Magn Reson Med 6:92–98PubMed
14.
go back to reference Robitaille P-M, Robitaille PA, Brown GG, Browns GG (1991) An analysis of the pH-dependent chemical shift behaviour of phosphorus-containing metabolites. J Magn Reson 92:73–84CrossRef Robitaille P-M, Robitaille PA, Brown GG, Browns GG (1991) An analysis of the pH-dependent chemical shift behaviour of phosphorus-containing metabolites. J Magn Reson 92:73–84CrossRef
15.
go back to reference Graham RA, Meyer RA, Szwergold BS, Brown TR (1987) Observation of myo-inositol 1,2-(cyclic) phosphate in a Morris hepatoma by 31P NMR. J Biol Chem 262:35–37PubMed Graham RA, Meyer RA, Szwergold BS, Brown TR (1987) Observation of myo-inositol 1,2-(cyclic) phosphate in a Morris hepatoma by 31P NMR. J Biol Chem 262:35–37PubMed
16.
go back to reference Bates TE, Williams SR, Gadian DG (1989) Phosphodiesters in the liver: the effect of field strength on the 31P signal. Magn Reson Med 12:145–150PubMed Bates TE, Williams SR, Gadian DG (1989) Phosphodiesters in the liver: the effect of field strength on the 31P signal. Magn Reson Med 12:145–150PubMed
17.
go back to reference de Kruijff B, van den Besselaar AMPH, Cullis PR, van den Bosch H, van Deenen LLM (1978) Evidence for isotropic motion of phospholipids in liver microsomal membranes. A 31P-NMR study. Biochim Biophys Acta 514:1–8PubMed de Kruijff B, van den Besselaar AMPH, Cullis PR, van den Bosch H, van Deenen LLM (1978) Evidence for isotropic motion of phospholipids in liver microsomal membranes. A 31P-NMR study. Biochim Biophys Acta 514:1–8PubMed
18.
go back to reference Murphy EJ, Rajagopalan B, Brindle KM, Radda GK (1989) Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med 12:282–289PubMed Murphy EJ, Rajagopalan B, Brindle KM, Radda GK (1989) Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med 12:282–289PubMed
19.
go back to reference Buchli R, Meier D, Martin E, Boesiger P (1994) Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II. Muscle, liver, kidney. Magn Reson Med 32:453–458PubMed Buchli R, Meier D, Martin E, Boesiger P (1994) Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II. Muscle, liver, kidney. Magn Reson Med 32:453–458PubMed
20.
go back to reference Hultman E, Nilsson LH, Sahlin K. (1975) Adenine nucleotide content in human liver; normal values and fructose induced deplation. Scand J Clin Lab Invest 35:245–251PubMed Hultman E, Nilsson LH, Sahlin K. (1975) Adenine nucleotide content in human liver; normal values and fructose induced deplation. Scand J Clin Lab Invest 35:245–251PubMed
21.
go back to reference Matson GB, Meyerhoff DJ, Lawry TJ et al (1993) Use of computer simulations for quantitation of 31P ISIS MRS results. NMR Biomed 6:215–224PubMed Matson GB, Meyerhoff DJ, Lawry TJ et al (1993) Use of computer simulations for quantitation of 31P ISIS MRS results. NMR Biomed 6:215–224PubMed
22.
go back to reference Ljungberg M, Starck G, Vikhoff-Baaz B, Alpsten M, Ekholm S, Forssell-Aronsson E (2002) The magnitude of signal errors introduced by ISIS in quantitative 31P MRS. Magma 14:30–38CrossRefPubMed Ljungberg M, Starck G, Vikhoff-Baaz B, Alpsten M, Ekholm S, Forssell-Aronsson E (2002) The magnitude of signal errors introduced by ISIS in quantitative 31P MRS. Magma 14:30–38CrossRefPubMed
23.
go back to reference Kuesel AC, Stoyanova R, Aiken NR et al (1996) Quantitation of resonances in biological 31P NMR spectra via principal component analysis: potential and limitations. NMR Biomed 9:93–104CrossRefPubMed Kuesel AC, Stoyanova R, Aiken NR et al (1996) Quantitation of resonances in biological 31P NMR spectra via principal component analysis: potential and limitations. NMR Biomed 9:93–104CrossRefPubMed
24.
go back to reference Menon DK, Sargentoni J, Taylor-Robinson SD et al (1995) Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances. Hepatology 21:417–427CrossRefPubMed Menon DK, Sargentoni J, Taylor-Robinson SD et al (1995) Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances. Hepatology 21:417–427CrossRefPubMed
25.
go back to reference Zakian KL, D’Angelica M, Matei C et al (2000) A quantitativce assessement of liver metabolites during jaundice using three dimensional phosphorus chemical shift imaging. Magn Reson Imaging 18:181–187CrossRefPubMed Zakian KL, D’Angelica M, Matei C et al (2000) A quantitativce assessement of liver metabolites during jaundice using three dimensional phosphorus chemical shift imaging. Magn Reson Imaging 18:181–187CrossRefPubMed
26.
go back to reference Dixon RM, Angus PW, Rajagopalan B, Radda GK (1991) Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy. Br J Cancer 63:953–958PubMed Dixon RM, Angus PW, Rajagopalan B, Radda GK (1991) Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy. Br J Cancer 63:953–958PubMed
27.
go back to reference Cox IJ, Bell JD, Peden CJ et al (1992) In vivo and in vitro 31P magnetic resonance spectroscopy of focal hepatic malignancies. NMR Biomed 5:114–120PubMed Cox IJ, Bell JD, Peden CJ et al (1992) In vivo and in vitro 31P magnetic resonance spectroscopy of focal hepatic malignancies. NMR Biomed 5:114–120PubMed
28.
go back to reference Brinkmann G, Melchert UH (1992) A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease. Magn Reson Imaging 10:949–956CrossRefPubMed Brinkmann G, Melchert UH (1992) A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease. Magn Reson Imaging 10:949–956CrossRefPubMed
29.
go back to reference Bell JD, Cox IJ, Sargentoni J et al (1993) A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver. Biochim Biophys Acta 1225:71–77CrossRefPubMed Bell JD, Cox IJ, Sargentoni J et al (1993) A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver. Biochim Biophys Acta 1225:71–77CrossRefPubMed
30.
go back to reference Yamane Y, Umeda M, O’Uchi T, Mitsushima T, Nakata K, Nagataki S (1994) Phosphorus-31 nuclear magnetic resonance in vivo spectroscopy of human liver during hepatitis A virus infection. Dig Dis Sci 39:33–38PubMed Yamane Y, Umeda M, O’Uchi T, Mitsushima T, Nakata K, Nagataki S (1994) Phosphorus-31 nuclear magnetic resonance in vivo spectroscopy of human liver during hepatitis A virus infection. Dig Dis Sci 39:33–38PubMed
31.
go back to reference Bourdel-Marchasson I, Biran M, Thiaudiere E et al (1996) 31P magnetic resonance spectroscopy of human liver in elderly patients: changes according to nutritional status and inflammatory state. Metabolism 45:1059–1061PubMed Bourdel-Marchasson I, Biran M, Thiaudiere E et al (1996) 31P magnetic resonance spectroscopy of human liver in elderly patients: changes according to nutritional status and inflammatory state. Metabolism 45:1059–1061PubMed
32.
go back to reference Cox IJ (1996) Development and applications of in vivo clinical magnetic resonance spectroscopy. Prog Biophys Mol Biol 65:45–81CrossRefPubMed Cox IJ (1996) Development and applications of in vivo clinical magnetic resonance spectroscopy. Prog Biophys Mol Biol 65:45–81CrossRefPubMed
33.
go back to reference Dagnelie PC, Sijens PE, Kraus DJ, Planting AS, van Dijk P (1999) Abnormal liver metabolism in cancer patients detected by (31)P MR spectroscopy. NMR Biomed 12:535–544CrossRefPubMed Dagnelie PC, Sijens PE, Kraus DJ, Planting AS, van Dijk P (1999) Abnormal liver metabolism in cancer patients detected by (31)P MR spectroscopy. NMR Biomed 12:535–544CrossRefPubMed
34.
go back to reference Mann DV, Lam WW, Magnus Hjelm N et al (2002) Biliary drainage for obstructive jaundice enhances hepatic energy status in humans: a 31-phosphorus magnetic resonance spectroscopy study. Gut 50:118–122CrossRefPubMed Mann DV, Lam WW, Magnus Hjelm N et al (2002) Biliary drainage for obstructive jaundice enhances hepatic energy status in humans: a 31-phosphorus magnetic resonance spectroscopy study. Gut 50:118–122CrossRefPubMed
35.
go back to reference Angus PW, Dixon RM, Rajagopalan B et al (1990) A study of patients with alcoholic liver disease by 31P nuclear magnetic resonance spectroscopy. Clin Sci (Colch) 78:33–38 Angus PW, Dixon RM, Rajagopalan B et al (1990) A study of patients with alcoholic liver disease by 31P nuclear magnetic resonance spectroscopy. Clin Sci (Colch) 78:33–38
36.
go back to reference Munakata T, Griffiths RD, Martin PA, Jenkins SA, Shields R, Edwards RH (1993) An in vivo 31P MRS study of patients with liver cirrhosis: progress towards a non-invasive assessment of disease severity. NMR Biomed 6:168–172PubMed Munakata T, Griffiths RD, Martin PA, Jenkins SA, Shields R, Edwards RH (1993) An in vivo 31P MRS study of patients with liver cirrhosis: progress towards a non-invasive assessment of disease severity. NMR Biomed 6:168–172PubMed
37.
go back to reference Taylor-Robinson SD, Thomas EL, Sargentoni J, Marcus CD, Davidson BR, Bell JD (1995) Cirrhosis of the human liver: an in vitro 31P nuclear magnetic resonance study. Biochim Biophys Acta 1272:113–118CrossRefPubMed Taylor-Robinson SD, Thomas EL, Sargentoni J, Marcus CD, Davidson BR, Bell JD (1995) Cirrhosis of the human liver: an in vitro 31P nuclear magnetic resonance study. Biochim Biophys Acta 1272:113–118CrossRefPubMed
38.
go back to reference van Wassenaer-van Hall HN, van der Grond J, van Hattum J, Kooijman C, Hoogenraad TU, Mali WP (1995) standardized serum, clinical, and histological changes in diffuse liver disease. Hepatology 21:443–449CrossRefPubMed van Wassenaer-van Hall HN, van der Grond J, van Hattum J, Kooijman C, Hoogenraad TU, Mali WP (1995) standardized serum, clinical, and histological changes in diffuse liver disease. Hepatology 21:443–449CrossRefPubMed
39.
go back to reference Menon DK, Harris M, Sargentoni J, Taylor-Robinson SD, Cox IJ, Morgan MY (1995) In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers. Gastroenterology 108:776–788PubMed Menon DK, Harris M, Sargentoni J, Taylor-Robinson SD, Cox IJ, Morgan MY (1995) In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers. Gastroenterology 108:776–788PubMed
40.
go back to reference Taylor-Robinson SD, Sargentoni J, Bell JD et al (1997) In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver. Liver 17:198–209PubMed Taylor-Robinson SD, Sargentoni J, Bell JD et al (1997) In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver. Liver 17:198–209PubMed
41.
go back to reference Jalan R, Sargentoni J, Coutts GA et al (1996) Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models. Gut 39:141–146PubMed Jalan R, Sargentoni J, Coutts GA et al (1996) Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models. Gut 39:141–146PubMed
42.
go back to reference Lim AK, Patel N, Hamilton G, Hajnal JV, Goldin RD, Taylor-Robinson SD (2003) The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C. Hepatology 37:788–794CrossRefPubMed Lim AK, Patel N, Hamilton G, Hajnal JV, Goldin RD, Taylor-Robinson SD (2003) The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C. Hepatology 37:788–794CrossRefPubMed
43.
go back to reference Kiyono K, Shibata A, Sone S et al (1998) Relationship of 31P MR spectroscopy to the histopathological grading of chronic hepatitis and response to therapy. Acta Radiol 39:309–314PubMed Kiyono K, Shibata A, Sone S et al (1998) Relationship of 31P MR spectroscopy to the histopathological grading of chronic hepatitis and response to therapy. Acta Radiol 39:309–314PubMed
44.
go back to reference Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter—interaction with feedback modifiers. Biochemistry 7:4030 Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter—interaction with feedback modifiers. Biochemistry 7:4030
45.
go back to reference Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl AM (1999) Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. J Am Med Assoc 282:1659–1664CrossRef Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl AM (1999) Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. J Am Med Assoc 282:1659–1664CrossRef
Metadata
Title
Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease
Authors
Bengt Norén
Peter Lundberg
Marcus Ressner
Staffan Wirell
Sven Almer
Örjan Smedby
Publication date
01-01-2005
Publisher
Springer-Verlag
Published in
European Radiology / Issue 1/2005
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-004-2434-x

Other articles of this Issue 1/2005

European Radiology 1/2005 Go to the issue