Journal of Hepatology
Volume 51, Issue 3 , Pages 433-445 , September 2009

Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance

  • Nina F. Schwenzer

      Affiliations

    • Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
  • ,
  • Fabian Springer

      Affiliations

    • Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
  • ,
  • Christina Schraml

      Affiliations

    • Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
  • ,
  • Norbert Stefan

      Affiliations

    • Department of Endocrinology and Metabolism, Eberhard-Karls University, Tübingen, Germany
  • ,
  • Jürgen Machann

      Affiliations

    • Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
  • ,
  • Fritz Schick

      Affiliations

    • Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology, Eberhard-Karls University, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 7071 2980543; fax: +49 7071 295392.

References 

  1. Angulo P. Obesity and nonalcoholic fatty liver disease. Nutr Rev. 2007;65:S57–S63
  2. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–1393
  3. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999;29:664–669
  4. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–121
  5. Stefan N, Kantartzis K, Haring HU. Causes and metabolic consequences of fatty liver. Endocr Rev. 2008;29:939–960
  6. Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007;24:1–6
  7. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008;168:1609–1616
  8. Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab. 2007;92:3490–3497
  9. Roden M. Mechanisms of disease: hepatic steatosis in type 2 diabetes – pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab. 2006;2:335–348
  10. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Krober SM, et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care. 2006;29:853–857
  11. Reinehr T, Roth CL. Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese children before and after weight loss. J Clin Endocrinol Metab. 2008;93:4479–4485
  12. Auberger P, Falquerho L, Contreres JO, Pages G, Le Cam G, Rossi B, et al. Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell. 1989;58:631–640
  13. Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Haring HU, et al. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS ONE. 2008;3:e1765
  14. Stefan N, Fritsche A, Weikert C, Boeing H, Joost HG, Haring HU, et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes. 2008;57:2762–2767
  15. Ix JH, Wassel CL, Kanaya AM, Vittinghoff E, Johnson KC, Koster A, et al. Fetuin-A and incident diabetes mellitus in older persons. JAMA. 2008;300:182–188
  16. Stefan N, Haring HU, Schulze MB. Association of fetuin-A level and diabetes risk. JAMA. 2008;300:2247;author reply 2247–2248
  17. Weikert C, Stefan N, Schulze MB, Pischon T, Berger K, Joost HG, et al. Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke. Circulation. 2008;118:2555–2562
  18. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321
  19. Wanless IR, Shiota K. The pathogenesis of nonalcoholic steatohepatitis and other fatty liver diseases: a four-step model including the role of lipid release and hepatic venular obstruction in the progression to cirrhosis. Semin Liver Dis. 2004;24:99–106
  20. Reuben A. Alcohol and the liver. Curr Opin Gastroenterol. 2007;23:283–291
  21. Reuben A. Alcohol and the liver. Curr Opin Gastroenterol. 2008;24:328–338
  22. Lefkowitch JH. Morphology of alcoholic liver disease. Clin Liver Dis. 2005;9:37–53
  23. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:S99–S112
  24. Harrison SA, Day CP. Benefits of lifestyle modification in NAFLD. Gut. 2007;56:1760–1769
  25. Tilg H, Kaser A. Treatment strategies in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol. 2005;2:148–155
  26. Stefan N, Machicao F, Staiger H, Machann J, Schick F, Tschritter O, et al. Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat. Diabetologia. 2005;48:2282–2291
  27. Kantartzis K, Thamer C, Peter A, Machann J, Schick F, Schraml C, et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2008 [Epub ahead of print].
  28. Kantartzis K, Machicao F, Machann J, Schick F, Fritsche A, Haring HU, et al. The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans. Clin Sci (Lond). 2009;116:531–537
  29. Bellentani S, Dalle Grave R, Suppini A, Marchesini G. Behavior therapy for nonalcoholic fatty liver disease: the need for a multidisciplinary approach. Hepatology. 2008;47:746–754
  30. Comar KM, Sterling RK. Review article: drug therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2006;23:207–215
  31. Joseph AE, Saverymuttu SH, al-Sam S, Cook MG, Maxwell JD. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol. 1991;43:26–31
  32. Valls C, Iannacconne R, Alba E, Murakami T, Hori M, Passariello R, et al. Fat in the liver: diagnosis and characterization. Eur Radiol. 2006;16:2292–2308
  33. Oleszczuk A, Spannbauer M, Tannapfel A, Bluher M, Hengstler J, Pietsch UC, et al. Regenerative capacity differs between micro- and macrovesicular hepatic steatosis. Exp Toxicol Pathol. 2007;59:205–213
  34. Mansouri A, Fromenty B, Berson A, Robin MA, Grimbert S, Beaugrand M, et al. Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients. J Hepatol. 1997;27:96–102
  35. Burt AD, Mutton A, Day CP. Diagnosis and interpretation of steatosis and steatohepatitis. Semin Diagn Pathol. 1998;15:246–258
  36. Jolly RA, Ciurlionis R, Morfitt D, Helgren M, Patterson R, Ulrich RG, et al. Microvesicular steatosis induced by a short chain fatty acid: effects on mitochondrial function and correlation with gene expression. Toxicol Pathol. 2004;32(Suppl 2):S19–S25
  37. Hamer OW, Aguirre DA, Casola G, Lavine JE, Woenckhaus M, Sirlin CB. Fatty liver: imaging patterns and pitfalls. Radiographics. 2006;26:1637–1653
  38. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–2474
  39. Fishbein M, Castro F, Cheruku S, Jain S, Webb B, Gleason T, et al. Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J Clin Gastroenterol. 2005;39:619–625
  40. Chalasani N, Wilson L, Kleiner DE, Cummings OW, Brunt EM, Unalp A. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J Hepatol. 2008;48:829–834
  41. Scheuer P, Lefkowitch J. Fatty liver and lesions in the alcoholic. In: Liver biopsy interpretation. 6th ed.. Philadelphia: Saunders; 2000;p. 111–129
  42. Brunt EM. Pathology of nonalcoholic steatohepatitis. Hepatol Res. 2005;33:68–71
  43. Garcia-Compean D, Cortes C. Transjugular liver biopsy. An update. Ann Hepatol. 2004;3:100–103
  44. Strassburg CP, Manns MP. Approaches to liver biopsy techniques – revisited. Semin Liver Dis. 2006;26:318–327
  45. Minervini MI, Ruppert K, Fontes P, Volpes R, Vizzini G, de Vera ME, et al. Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests. J Hepatol. 2009;50:501–510
  46. Nagai S, Fujimoto Y, Kamei H, Nakamura T, Kiuchi T. Mild hepatic macrovesicular steatosis may be a risk factor for hyperbilirubinaemia in living liver donors following right hepatectomy. Br J Surg. 2009;96:437–444
  47. Limanond P, Raman SS, Lassman C, Sayre J, Ghobrial RM, Busuttil RW, et al. Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology. 2004;230:276–280
  48. Selzner M, Clavien PA. Fatty liver in liver transplantation and surgery. Semin Liver Dis. 2001;21:105–113
  49. Vetelainen R, van Vliet A, Gouma DJ, van Gulik TM. Steatosis as a risk factor in liver surgery. Ann Surg. 2007;245:20–30
  50. Cowin GJ, Jonsson JR, Bauer JD, Ash S, Ali A, Osland EJ, et al. Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging. 2008;28:937–945
  51. Wieckowska A, McCullough AJ, Feldstein AE. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007;46:582–589
  52. Palmentieri B, de Sio I, La Mura V, Masarone M, Vecchione R, Bruno S, et al. The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis. 2006;38:485–489
  53. Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, et al. Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol. 1997;27:108–113
  54. Roldan-Valadez E, Favila R, Martinez-Lopez M, Uribe M, Mendez-Sanchez N. Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease. Ann Hepatol. 2008;7:212–220
  55. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed). 1986;292:13–15
  56. Debongnie JC, Pauls C, Fievez M, Wibin E. Prospective evaluation of the diagnostic accuracy of liver ultrasonography. Gut. 1981;22:130–135
  57. Foster KJ, Dewbury KC, Griffith AH, Wright R. The accuracy of ultrasound in the detection of fatty infiltration of the liver. Br J Radiol. 1980;53:440–442
  58. Graif M, Yanuka M, Baraz M, Blank A, Moshkovitz M, Kessler A, et al. Quantitative estimation of attenuation in ultrasound video images: correlation with histology in diffuse liver disease. Invest Radiol. 2000;35:319–324
  59. Steinmaurer HJ, Jirak P, Walchshofer J, Clodi PH. Accuracy of sonography in the diagnosis of diffuse liver parenchymal diseases – comparison of sonography and liver histology. Ultraschall Med. 1984;5:98–103
  60. Hamaguchi M, Kojima T, Itoh Y, Harano Y, Fujii K, Nakajima T, et al. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am J Gastroenterol. 2007;102:2708–2715
  61. Taylor KJ, Gorelick FS, Rosenfield AT, Riely CA. Ultrasonography of alcoholic liver disease with histological correlation. Radiology. 1981;141:157–161
  62. Meek DR, Mills PR, Gray HW, Duncan JG, Russell RI, McKillop JH. A comparison of computed tomography, ultrasound and scintigraphy in the diagnosis of alcoholic liver disease. Br J Radiol. 1984;57:23–27
  63. Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. Am J Roentgenol. 2007;189:W320–W323
  64. Ducommun JC, Goldberg HI, Korobkin M, Moss AA, Kressel HY. The relation of liver fat to computed tomography numbers: a preliminary experimental study in rabbits. Radiology. 1979;130:511–513
  65. Pamilo M, Sotaniemi EA, Suramo I, Lahde S, Arranto AJ. Evaluation of liver steatotic and fibrous content by computerized tomography and ultrasound. Scand J Gastroenterol. 1983;18:743–747
  66. Kawata R, Sakata K, Kunieda T, Saji S, Doi H, Nozawa Y. Quantitative evaluation of fatty liver by computed tomography in rabbits. Am J Roentgenol. 1984;142:741–746
  67. Karcaaltincaba M, Akhan O. Imaging of hepatic steatosis and fatty sparing. Eur J Radiol. 2007;61:33–43
  68. Mehta SR, Thomas EL, Bell JD, Johnston DG, Taylor-Robinson SD. Non-invasive means of measuring hepatic fat content. World J Gastroenterol. 2008;14:3476–3483
  69. Piekarski J, Goldberg HI, Royal SA, Axel L, Moss AA. Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. Radiology. 1980;137:727–729
  70. Hamer OW, Aguirre DA, Casola G, Sirlin CB. Imaging features of perivascular fatty infiltration of the liver: initial observations. Radiology. 2005;237:159–169
  71. Park SH, Kim PN, Kim KW, Lee SW, Yoon SE, Park SW, et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology. 2006;239:105–112
  72. Iwasaki M, Takada Y, Hayashi M, Minamiguchi S, Haga H, Maetani Y, et al. Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation. 2004;78:1501–1505
  73. Johnston RJ, Stamm ER, Lewin JM, Hendrick RE, Archer PG. Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements. Abdom Imaging. 1998;23:409–415
  74. Kodama Y, Ng CS, Wu TT, Ayers GD, Curley SA, Abdalla EK, et al. Comparison of CT methods for determining the fat content of the liver. Am J Roentgenol. 2007;188:1307–1312
  75. Jacobs JE, Birnbaum BA, Shapiro MA, Langlotz CP, Slosman F, Rubesin SE, et al. Diagnostic criteria for fatty infiltration of the liver on contrast-enhanced helical CT. Am J Roentgenol. 1998;171:659–664
  76. Panicek DM, Giess CS, Schwartz LH. Qualitative assessment of liver for fatty infiltration on contrast-enhanced CT: is muscle a better standard of reference than spleen?. J Comput Assist Tomogr. 1997;21:699–705
  77. Mendler MH, Bouillet P, Le Sidaner A, Lavoine E, Labrousse F, Sautereau D, et al. Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload. J Hepatol. 1998;28:785–794
  78. Raptopoulos V, Karellas A, Bernstein J, Reale FR, Constantinou C, Zawacki JK. Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. Am J Roentgenol. 1991;157:721–725
  79. Flohr TG, McCollough CH, Bruder H, Petersilka M, Gruber K, Suss C, et al. First performance evaluation of a dual-source CT (DSCT) system. Eur Radiol. 2006;16:256–268
  80. Wang B, Gao Z, Zou Q, Li L. Quantitative diagnosis of fatty liver with dual-energy CT. An experimental study in rabbits. Acta Radiol. 2003;44:92–97
  81. Birnbaum BA, Hindman N, Lee J, Babb JS. Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom. Radiology. 2007;242:109–119
  82. Li CW, Kuo YC, Chen CY, Kuo YT, Chiu YY, She FO, et al. Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3T. Magn Reson Med. 2005;53:770–776
  83. Bell JD, Cox IJ, Sargentoni J, Peden CJ, Menon DK, Foster CS, et al. A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver. Biochim Biophys Acta. 1993;1225:71–77
  84. Longo R, Pollesello P, Ricci C, Masutti F, Kvam BJ, Bercich L, et al. Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J Magn Reson Imaging. 1995;5:281–285
  85. Longo R, Ricci C, Masutti F, Vidimari R, Croce LS, Bercich L, et al. Fatty infiltration of the liver. Quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography. Invest Radiol. 1993;28:297–302
  86. Szczepaniak LS, Babcock EE, Schick F, Dobbins RL, Garg A, Burns DK, et al. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol. 1999;276:E977–E989
  87. Thomsen C, Becker U, Winkler K, Christoffersen P, Jensen M, Henriksen O. Quantification of liver fat using magnetic resonance spectroscopy. Magn Reson Imaging. 1994;12:487–495
  88. Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann NY Acad Sci. 1987;508:333–348
  89. Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hanicke W, Sauter R. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med. 1989;9:79–93
  90. Pykett IL, Rosen BR. Nuclear magnetic resonance: in vivo proton chemical shift imaging. Work in progress. Radiology. 1983;149:197–201
  91. Skoch A, Jiru F, Bunke J. Spectroscopic imaging: basic principles. Eur J Radiol. 2008;67:230–239
  92. Irwan R, Edens MA, Sijens PE. Assessment of the variations in fat content in normal liver using a fast MR imaging method in comparison with results obtained by spectroscopic imaging. Eur Radiol. 2008;18:806–813
  93. Sijens PE, Smit GP, Borgdorff MA, Kappert P, Oudkerk M. Multiple voxel 1H MR spectroscopy of phosphorylase-b kinase deficient patients (GSD IXa) showing an accumulation of fat in the liver that resolves with aging. J Hepatol. 2006;45:851–855
  94. Machann J, Stefan N, Schick F. 1H MR spectroscopy of skeletal muscle, liver and bone marrow. Eur J Radiol. 2008;67:275–284
  95. Machann J, Thamer C, Schnoedt B, Stefan N, Haring HU, Claussen CD, et al. Hepatic lipid accumulation in healthy subjects: a comparative study using spectral fat-selective MRI and volume-localized 1H-MR spectroscopy. Magn Reson Med. 2006;55:913–917
  96. Thomas EL, Hamilton G, Patel N, O’Dwyer R, Dore CJ, Goldin RD, et al. Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study. Gut. 2005;54:122–127
  97. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:E462–E468
  98. Marsman H, Matsushita T, Dierkhising R, Kremers W, Rosen C, Burgart L, et al. Assessment of donor liver steatosis: pathologist or automated software?. Hum Pathol. 2004;35:430–435
  99. Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355:2297–2307
  100. Thamer C, Machann J, Stefan N, Schafer SA, Machicao F, Staiger H, et al. Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. J Clin Endocrinol Metab. 2008;93:1497–1500
  101. Thomas EL, Brynes AE, Hamilton G, Patel N, Spong A, Goldin RD, et al. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. World J Gastroenterol. 2006;12:5813–5819
  102. Thomas EL, Potter E, Tosi I, Fitzpatrick J, Hamilton G, Amber V, et al. Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content. Atherosclerosis. 2007;195:e181–e190
  103. Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004;53:2169–2176
  104. Westerbacka J, Lammi K, Hakkinen AM, Rissanen A, Salminen I, Aro A, et al. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab. 2005;90:2804–2809
  105. Stumvoll M. Control of glycaemia: from molecules to men. Minkowski Lecture 2003. Diabetologia. 2004;47:770–781
  106. Stefan N, Schafer S, Machicao F, Machann J, Schick F, Claussen CD, et al. Liver fat and insulin resistance are independently associated with the −514C>T polymorphism of the hepatic lipase gene. J Clin Endocrinol Metab. 2005;90:4238–4243
  107. Kantartzis K, Rittig K, Balletshofer B, Machann J, Schick F, Porubska K, et al. The relationships of plasma adiponectin with a favorable lipid profile, decreased inflammation, and less ectopic fat accumulation depend on adiposity. Clin Chem. 2006;52:1934–1942
  108. Kantartzis K, Fritsche A, Machicao F, Stumvoll M, Machann J, Schick F, et al. Upstream transcription factor 1 gene polymorphisms are associated with high antilipolytic insulin sensitivity and show gene–gene interactions. J Mol Med. 2007;85:55–61
  109. Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care. 2007;30:1173–1178
  110. Perseghin G, Lattuada G, De Cobelli F, Esposito A, Belloni E, Canu T, et al. Serum retinol-binding protein-4, leptin, and adiponectin concentrations are related to ectopic fat accumulation. J Clin Endocrinol Metab. 2007;92:4883–4888
  111. Weyrich P, Machicao F, Staiger H, Simon P, Thamer C, Machann J, et al. Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites. Diabetologia. 2007;50:2097–2106
  112. Stefan N, Peter A, Cegan A, Staiger H, Machann J, Schick F, et al. Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans. Diabetologia. 2008;51:648–656
  113. Haupt A, Thamer C, Machann J, Kirchhoff K, Stefan N, Tschritter O, et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring). 2008;16:1969–1972
  114. Silbernagel G, Stefan N, Hoffmann MM, Machicao-Arano F, Machann J, Schick F, et al. The L162V polymorphism of the peroxisome proliferator activated receptor alpha gene (PPARA) is not associated with type 2 diabetes, BMI or body fat composition. Exp Clin Endocrinol Diabetes. 2009;117:113–118
  115. Dixon WT. Simple proton spectroscopic imaging. Radiology. 1984;153:189–194
  116. Fishbein MH, Gardner KG, Potter CJ, Schmalbrock P, Smith MA. Introduction of fast MR imaging in the assessment of hepatic steatosis. Magn Reson Imaging. 1997;15:287–293
  117. Machann J, Bachmann OP, Brechtel K, Dahl DB, Wietek B, Klumpp B, et al. Lipid content in the musculature of the lower leg assessed by fat selective MRI: intra- and interindividual differences and correlation with anthropometric and metabolic data. J Magn Reson Imaging. 2003;17:350–357
  118. Fishbein MH, Stevens WR. Rapid MRI using a modified Dixon technique: a non-invasive and effective method for detection and monitoring of fatty metamorphosis of the liver. Pediatr Radiol. 2001;31:806–809
  119. Namimoto T, Yamashita Y, Mitsuzaki K, Nakayama Y, Makita O, Kadota M, et al. Adrenal masses: quantification of fat content with double-echo chemical shift in-phase and opposed-phase FLASH MR images for differentiation of adrenal adenomas. Radiology. 2001;218:642–646
  120. Park HW, Kim YH, Cho ZH. Fast gradient-echo chemical-shift imaging. Magn Reson Med. 1988;7:340–345
  121. Chen Q, Stock KW, Prasad PV, Hatabu H. Fast magnetic resonance imaging techniques. Eur J Radiol. 1999;29:90–100
  122. Hussain HK, Chenevert TL, Londy FJ, Gulani V, Swanson SD, McKenna BJ, et al. Hepatic fat fraction: MR imaging for quantitative measurement and display – early experience. Radiology. 2005;237:1048–1055
  123. Alustiza JM, Castiella A. Liver fat and iron at in-phase and opposed-phase MR imaging. Radiology. 2008;246:641
  124. Kim HJ, Byun JH, Park SH, Shin YM, Kim PN, Ha HK, et al. Focal fatty replacement of the pancreas: usefulness of chemical shift MRI. Am J Roentgenol. 2007;188:429–432
  125. Westphalen AC, Qayyum A, Yeh BM, Merriman RB, Lee JA, Lamba A, et al. Liver fat: effect of hepatic iron deposition on evaluation with opposed-phase MR imaging. Radiology. 2007;242:450–455
  126. Zhang X, Tengowski M, Fasulo L, Botts S, Suddarth SA, Johnson GA. Measurement of fat/water ratios in rat liver using 3D three-point dixon MRI. Magn Reson Med. 2004;51:697–702
  127. Levenson H, Greensite F, Hoefs J, Friloux L, Applegate G, Silva E, et al. Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5T vs biopsy. Am J Roentgenol. 1991;156:307–312
  128. Glover GH, Schneider E. Three-point Dixon technique for true water/fat decomposition with B0 inhomogeneity correction. Magn Reson Med. 1991;18:371–383
  129. Glover GH. Multipoint Dixon technique for water and fat proton and susceptibility imaging. J Magn Reson Imaging. 1991;1:521–530
  130. Borrello JA, Chenevert TL, Meyer CR, Aisen AM, Glazer GM. Chemical shift-based true water and fat images: regional phase correction of modified spin-echo MR images. Radiology. 1987;164:531–537
  131. Lodes CC, Felmlee JP, Ehman RL, Sehgal CM, Greenleaf JF, Glover GH, et al. Proton MR chemical shift imaging using double and triple phase contrast acquisition methods. J Comput Assist Tomogr. 1989;13:855–861
  132. Szumowski J, Coshow WR, Li F, Quinn SF. Phase unwrapping in the three-point Dixon method for fat suppression MR imaging. Radiology. 1994;192:555–561
  133. Szumowski J, Coshow W, Li F, Coombs B, Quinn SF. Double-echo three-point-Dixon method for fat suppression MRI. Magn Reson Med. 1995;34:120–124
  134. Yeung HN, Kormos DW. Separation of true fat and water images by correcting magnetic field inhomogeneity in situ. Radiology. 1986;159:783–786
  135. Coombs BD, Szumowski J, Coshow W. Two-point Dixon technique for water–fat signal decomposition with B0 inhomogeneity correction. Magn Reson Med. 1997;38:884–889
  136. Rybicki FJ, Chung T, Reid J, Jaramillo D, Mulkern RV, Ma J. Fast three-point dixon MR imaging using low-resolution images for phase correction: a comparison with chemical shift selective fat suppression for pediatric musculoskeletal imaging. Am J Roentgenol. 2001;177:1019–1023
  137. Mehta SR, Thomas EL, Bell JD, Johnston DG, Taylor-Robinson SD. Non-invasive means of measuring hepatic fat content. World J Gastroenterol. 2008;14:3476–3483
  138. Guiu B, Petit JM, Loffroy R, Ben Salem D, Aho S, Masson D, et al. Quantification of liver fat content: comparison of triple-echo chemical shift gradient-echo imaging and in vivo proton MR spectroscopy. Radiology. 2009;250:95–102
  139. Reeder SB, Pineda AR, Wen Z, Shimakawa A, Yu H, Brittain JH, et al. Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): application with fast spin-echo imaging. Magn Reson Med. 2005;54:636–644
  140. Reeder SB, McKenzie CA, Pineda AR, Yu H, Shimakawa A, Brau AC, et al. Water–fat separation with IDEAL gradient-echo imaging. J Magn Reson Imaging. 2007;25:644–652
  141. Liu CY, McKenzie CA, Yu H, Brittain JH, Reeder SB. Fat quantification with IDEAL gradient echo imaging: correction of bias from T(1) and noise. Magn Reson Med. 2007;58:354–364
  142. Schick F, Machann J, Brechtel K, Strempfer A, Klumpp B, Stein DT, et al. MRI of muscular fat. Magn Reson Med. 2002;47:720–727
  143. Schwenzer NF, Machann J, Martirosian P, Stefan N, Schraml C, Fritsche A, et al. Quantification of pancreatic lipomatosis and liver steatosis by MRI: comparison of in/opposed-phase and spectral–spatial excitation techniques. Invest Radiol. 2008;43:330–337
  144. O’Regan DP, Callaghan MF, Wylezinska-Arridge M, Fitzpatrick J, Naoumova RP, Hajnal JV, et al. Liver fat content and T2: simultaneous measurement by using breath-hold multiecho MR imaging at 3.0T-feasibility. Radiology. 2008;247:550–557
  145. Lewin M, Poujol-Robert A, Boelle PY, Wendum D, Lasnier E, Viallon M, et al. Diffusion-weighted magnetic resonance imaging for the assessment of fibrosis in chronic hepatitis C. Hepatology. 2007;46:658–665
  146. Annet L, Peeters F, Abarca-Quinones J, Leclercq I, Moulin P, Van Beers BE. Assessment of diffusion-weighted MR imaging in liver fibrosis. J Magn Reson Imaging. 2007;25:122–128
  147. Huwart L, Sempoux C, Salameh N, Jamart J, Annet L, Sinkus R, et al. Liver fibrosis: noninvasive assessment with MR elastography versus aspartate aminotransferase-to-platelet ratio index. Radiology. 2007;245:458–466
  148. Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009;7:234–238
  149. Yoneda M, Yoneda M, Mawatari H, Fujita K, Endo H, Iida H, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis. 2008;40:371–378
  150. Wells RG. The role of matrix stiffness in hepatic stellate cell activation and liver fibrosis. J Clin Gastroenterol. 2005;39:S158–S161
  151. Roulot D, Czernichow S, Le Clesiau H, Costes JL, Vergnaud AC, Beaugrand M. Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol. 2008;48:606–613
  152. Georges PC, Hui JJ, Gombos Z, McCormick ME, Wang AY, Uemura M, et al. Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007;293:G1147–G1154
  153. Huwart L, Sempoux C, Vicaut E, Salameh N, Annet L, Danse E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135:32–40

 The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00390-0

doi: 10.1016/j.jhep.2009.05.023

Journal of Hepatology
Volume 51, Issue 3 , Pages 433-445 , September 2009