Fatty Liver Disease

  • Scott C. Beeman
  • Joel R. GarbowEmail author


Fatty liver disease is a debilitating, expensive, and potentially fatal pathology of rapidly increasing incidence. Currently, detection, characterization, and diagnosis of fatty liver disease rely heavily on blood serum biomarkers and biopsy—methods which are either nonspecific to fatty liver disease (serum biomarkers) or invasive and highly focal (biopsy). In this chapter, we detail state-of-the-art imaging techniques for detecting and quantifying fatty liver disease, its precursors, and its downstream complications. Methods for detecting fatty liver with ultrasound (US) and computed tomography (CT) are discussed first. Special emphasis is then placed on magnetic resonance (MR)-based techniques, which are inherently sensitive to the molecular composition of tissue and can quantify the so-called proton density fat fraction of the liver with extremely high accuracy and precision. Finally, preclinical and investigational techniques, including novel US, CT, and MR methods, as well as positron emission tomography and optical imaging techniques, are discussed.


Hepatorenal contrast Liver-spleen ratio Magnetic resonance spectroscopy Dixon method Signal fat fraction Proton density fat fraction 


  1. 1.
    NIDDK. Nonalcoholic Steatohepatitis. In: NIH, editor. U.S. Department of Health and Human Services; 2006.
  2. 2.
    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114(4):842–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60(1):110–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Poynard T, Ratziu V, Naveau S, Thabut D, Charlotte F, Messous D, et al. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol. 2005;4:10.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006;6:6.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Taylor KJ, McCready VR. A clinical evaluation of grey-scale ultrasonography. Br J Radiol. 1976;49(579):244–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Yilmaz Y, Dolar E, Ulukaya E, Akgoz S, Keskin M, Kiyici M, et al. Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis. World J Gastroenterol. 2007;13(6):837–44.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Wieckowska A, Feldstein AE. Nonalcoholic fatty liver disease in the pediatric population: a review. Curr Opin Pediatr. 2005;17(5):636–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Tarantino G, Conca P, Coppola A, Vecchione R, Di Minno G. Serum concentrations of the tissue polypeptide specific antigen in patients suffering from non-alcoholic steatohepatitis. Eur J Clin Investig. 2007;37(1):48–53.CrossRefGoogle Scholar
  10. 10.
    Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123(3):745–50.PubMedCrossRefGoogle Scholar
  11. 11.
    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(7):485–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Mottin CC, Moretto M, Padoin AV, Swarowsky AM, Toneto MG, Glock L, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg. 2004;14(5):635–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol. 2007;189(6):W320–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci. 2010;55(3):560–78.PubMedCrossRefGoogle Scholar
  15. 15.
    Schwenzer NF, Springer F, Schraml C, Stefan N, Machann J, Schick F. Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol. 2009;51(3):433–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound. 1996;24(1):25–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Webb M, Yeshua H, Zelber-Sagi S, Santo E, Brazowski E, Halpern Z, et al. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol. 2009;192(4):909–14.PubMedCrossRefGoogle Scholar
  18. 18.
    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(12):2708–15.PubMedCrossRefGoogle Scholar
  19. 19.
    Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29(12):1705–13.PubMedCrossRefGoogle Scholar
  20. 20.
    Castera L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010;51(3):828–35.PubMedGoogle Scholar
  21. 21.
    de Ledinghen V, Vergniol J, Foucher J, El-Hajbi F, Merrouche W, Rigalleau V. Feasibility of liver transient elastography with FibroScan using a new probe for obese patients. Liver Int. 2010;30(7):1043–8.PubMedCrossRefGoogle Scholar
  22. 22.
    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(2):511–3.PubMedCrossRefGoogle Scholar
  23. 23.
    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(3):727–9.PubMedCrossRefGoogle Scholar
  24. 24.
    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(1):105–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Hamer OW, Aguirre DA, Casola G, Sirlin CB. Imaging features of perivascular fatty infiltration of the liver: initial observations. Radiology. 2005;237(1):159–69.PubMedCrossRefGoogle Scholar
  26. 26.
    Boyce CJ, Pickhardt PJ, Kim DH, Taylor AJ, Winter TC, Bruce RJ, et al. Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR Am J Roentgenol. 2010;194(3):623–8.PubMedCrossRefGoogle Scholar
  27. 27.
    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(10):1501–5.PubMedCrossRefGoogle Scholar
  28. 28.
    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(4):409–15.PubMedCrossRefGoogle Scholar
  29. 29.
    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. AJR Am J Roentgenol. 1998;171(3):659–64.PubMedCrossRefGoogle Scholar
  30. 30.
    Varenika V, Fu Y, Maher JJ, Gao D, Kakar S, Cabarrus MC, et al. Hepatic fibrosis: evaluation with semiquantitative contrast-enhanced CT. Radiology. 2013;266(1):151–8.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Haacke EM. Magnetic resonance imaging: physical principles and sequence design. New York: John Wiley & Sons; 1999. p. 914.Google Scholar
  32. 32.
    Levitt MH. Spin dynamics : basics of nuclear magnetic resonance. Chichester. New York: John Wiley & Sons; 2001. p. 686.Google Scholar
  33. 33.
    Kim H, Taksali SE, Dufour S, Befroy D, Goodman TR, Petersen KF, et al. Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL. Magn Reson Med. 2008;59(3):521–7.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Meisamy S, Hines CD, Hamilton G, Sirlin CB, McKenzie CA, Yu H, et al. Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy. Radiology. 2011;258(3):767–75.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Yokoo T, Bydder M, Hamilton G, Middleton MS, Gamst AC, Wolfson T, et al. Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T. Radiology. 2009;251(1):67–76.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Yokoo T, Shiehmorteza M, Hamilton G, Wolfson T, Schroeder ME, Middleton MS, et al. Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. Radiology. 2011;258(3):749–59.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Pineda N, Sharma P, Xu Q, Hu X, Vos M, Martin DR. Measurement of hepatic lipid: high-speed T2-corrected multiecho acquisition at 1H MR spectroscopy—a rapid and accurate technique. Radiology. 2009;252(2):568–76.PubMedCrossRefGoogle Scholar
  38. 38.
    Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging. 2011;34(4):729–49.PubMedCrossRefGoogle Scholar
  39. 39.
    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(4):937–45.PubMedCrossRefGoogle Scholar
  40. 40.
    d'Assignies G, Ruel M, Khiat A, Lepanto L, Chagnon M, Kauffmann C, et al. Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods. Eur Radiol. 2009;19(8):2033–40.PubMedCrossRefGoogle Scholar
  41. 41.
    Hamilton G, Middleton MS, Bydder M, Yokoo T, Schwimmer JB, Kono Y, et al. Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification. J Magn Reson Imaging. 2009;30(1):145–52.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Hamilton G, Yokoo T, Bydder M, Cruite I, Schroeder ME, Sirlin CB, et al. In vivo characterization of the liver fat (1)H MR spectrum. NMR Biomed. 2011;24(7):784–90.PubMedCrossRefGoogle Scholar
  43. 43.
    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(3):281–5.PubMedCrossRefGoogle Scholar
  44. 44.
    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. Investig Radiol. 1993;28(4):297–302.CrossRefGoogle Scholar
  45. 45.
    McPherson S, Jonsson JR, Cowin GJ, O'Rourke P, Clouston AD, Volp A, et al. Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered. J Hepatol. 2009;51(2):389–97.PubMedCrossRefGoogle Scholar
  46. 46.
    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(3):487–95.PubMedCrossRefGoogle Scholar
  47. 47.
    Borra RJ, Salo S, Dean K, Lautamaki R, Nuutila P, Komu M, et al. Nonalcoholic fatty liver disease: rapid evaluation of liver fat content with in-phase and out-of-phase MR imaging. Radiology. 2009;250(1):130–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Bydder M, Yokoo T, Hamilton G, Middleton MS, Chavez AD, Schwimmer JB, et al. Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging. 2008;26(3):347–59.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    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(3):287–93.PubMedCrossRefGoogle Scholar
  50. 50.
    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(1):95–102.PubMedCrossRefGoogle Scholar
  51. 51.
    He T, Gatehouse PD, Kirk P, Mohiaddin RH, Pennell DJ, Firmin DN. Myocardial T*2 measurement in iron-overloaded thalassemia: an ex vivo study to investigate optimal methods of quantification. Magn Reson Med. 2008;60(2):350–6.PubMedCrossRefGoogle Scholar
  52. 52.
    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(3):1048–55.PubMedCrossRefGoogle Scholar
  53. 53.
    Kawamitsu H, Kaji Y, Ohara T, Sugimura K. Feasibility of quantitative intrahepatic lipid imaging applied to the magnetic resonance dual gradient echo sequence. Magn Reson Med Sci. 2003;2(1):47–50.PubMedCrossRefGoogle Scholar
  54. 54.
    Kovanlikaya A, Guclu C, Desai C, Becerra R, Gilsanz V. Fat quantification using three-point dixon technique: in vitro validation. Acad Radiol. 2005;12(5):636–9.PubMedCrossRefGoogle Scholar
  55. 55.
    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 1.5 T vs biopsy. AJR Am J Roentgenol. 1991;156(2):307–12.PubMedCrossRefGoogle Scholar
  56. 56.
    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(2):354–64.PubMedCrossRefGoogle Scholar
  57. 57.
    Mitchell DG, Kim I, Chang TS, Vinitski S, Consigny PM, Saponaro SA, et al. Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans. Investig Radiol. 1991;26(12):1041–52.CrossRefGoogle Scholar
  58. 58.
    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 3.0 T—feasibility. Radiology. 2008;247(2):550–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Pacifico L, Celestre M, Anania C, Paolantonio P, Chiesa C, Laghi A. MRI and ultrasound for hepatic fat quantification: relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease. Acta Paediatr. 2007;96(4):542–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Qayyum A, Goh JS, Kakar S, Yeh BM, Merriman RB, Coakley FV. Accuracy of liver fat quantification at MR imaging: comparison of out-of-phase gradient-echo and fat-saturated fast spin-echo techniques—initial experience. Radiology. 2005;237(2):507–11.PubMedCrossRefGoogle Scholar
  61. 61.
    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(3):644–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Reeder SB, Robson PM, Yu H, Shimakawa A, Hines CD, McKenzie CA, et al. Quantification of hepatic steatosis with MRI: the effects of accurate fat spectral modeling. J Magn Reson Imaging. 2009;29(6):1332–9.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Rinella ME, McCarthy R, Thakrar K, Finn JP, Rao SM, Koffron AJ, et al. Dual-echo, chemical shift gradient-echo magnetic resonance imaging to quantify hepatic steatosis: implications for living liver donation. Liver Transpl. 2003;9(8):851–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Schuchmann S, Weigel C, Albrecht L, Kirsch M, Lemke A, Lorenz G, et al. Non-invasive quantification of hepatic fat fraction by fast 1.0, 1.5 and 3.0 T MR imaging. Eur J Radiol. 2007;62(3):416–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Yoshimitsu K, Kuroda Y, Nakamuta M, Taketomi A, Irie H, Tajima T, et al. Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: significance for living donors. J Magn Reson Imaging. 2008;28(3):678–84.PubMedCrossRefGoogle Scholar
  66. 66.
    Yu H, McKenzie CA, Shimakawa A, AT V, Brau AC, Beatty PJ, et al. Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. J Magn Reson Imaging. 2007;26(4):1153–61.PubMedCrossRefGoogle Scholar
  67. 67.
    Yu H, Shimakawa A, McKenzie CA, Brodsky E, Brittain JH, Reeder SB. Multiecho water-fat separation and simultaneous R2* estimation with multifrequency fat spectrum modeling. Magn Reson Med. 2008;60(5):1122–34.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Haase A, Frahm J, Matthaei D, Hanicke W, Bomsdorf H, Kunz D, et al. MR imaging using stimulated echoes (STEAM). Radiology. 1986;160(3):787–90.PubMedCrossRefGoogle Scholar
  69. 69.
    Bottomley PA, inventor. General electric company, assignee. Selective volume method for performing localized NMR spectroscopy; 1984.Google Scholar
  70. 70.
    Reeder SB, HH H, Sirlin CB. Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration. J Magn Reson Imaging. 2012;36(5):1011–4.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Dixon WT. Simple proton spectroscopic imaging. Radiology. 1984;153(1):189–94.PubMedCrossRefGoogle Scholar
  72. 72.
    Ma JF. Breath-hold water and fat imaging using a dual-echo two-point dixon technique with an efficient and robust phase-correction algorithm. Magn Reson Med. 2004;52(2):415–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Glover GH, Schneider E. Three-point Dixon technique for true water/fat decomposition with B0 inhomogeneity correction. Magn Reson Med. 1991;18(2):371–83.PubMedCrossRefGoogle Scholar
  74. 74.
    Glover GH. Multipoint Dixon technique for water and fat proton and susceptibility imaging. J Magn Reson Imaging. 1991;1(5):521–30.PubMedCrossRefGoogle Scholar
  75. 75.
    Middleton M, Hamilton G, Bydder M, Sirlin C, editors. How much fat is under the water peak in liver fat MR spectroscopy? Honolulu, Hawaii: International Society for Magnetic Resonance in Medicine; 2009.Google Scholar
  76. 76.
    Muthupillai R, Lomas DJ, Rossman PJ, Greenleaf JF, Manduca A, Ehman RL. Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. Science. 1995;269(5232):1854–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Othman SF, Xu H, Royston TJ, Magin RL. Microscopic magnetic resonance elastography (microMRE). Magn Reson Med. 2005;54(3):605–15.PubMedCrossRefGoogle Scholar
  78. 78.
    Yin M, Talwalkar JA, Glaser KJ, Manduca A, Grimm RC, Rossman PJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5(10):1207–13. e2.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Asbach P, Klatt D, Hamhaber U, Braun J, Somasundaram R, Hamm B, et al. Assessment of liver viscoelasticity using multifrequency MR elastography. Magn Reson Med. 2008;60(2):373–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Mariappan YK, Glaser KJ, Ehman RL. Magnetic resonance elastography: a review. Clin Anat. 2010;23(5):497–511.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Manduca A, Oliphant TE, Dresner MA, Mahowald JL, Kruse SA, Amromin E, et al. Magnetic resonance elastography: non-invasive mapping of tissue elasticity. Med Image Anal. 2001;5(4):237–54.PubMedCrossRefGoogle Scholar
  82. 82.
    Oliphant TE, Manduca A, Ehman RL, Greenleaf JF. Complex-valued stiffness reconstruction for magnetic resonance elastography by algebraic inversion of the differential equation. Magn Reson Med. 2001;45(2):299–310.PubMedCrossRefGoogle Scholar
  83. 83.
    Manduca A, Lake DS, Kruse SA, Ehman RL. Spatio-temporal directional filtering for improved inversion of MR elastography images. Med Image Anal. 2003;7(4):465–73.PubMedCrossRefGoogle Scholar
  84. 84.
    Rouviere O, Yin M, Dresner MA, Rossman PJ, Burgart LJ, Fidler JL, et al. MR elastography of the liver: preliminary results. Radiology. 2006;240(2):440–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Venkatesh SK, Yin M, Glockner JF, Takahashi N, Araoz PA, Talwalkar JA, et al. MR elastography of liver tumors: preliminary results. AJR Am J Roentgenol. 2008;190(6):1534–40.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Singh S, Venkatesh SK, Wang Z, Miller FH, Motosugi U, Low RN, et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: a systematic review and meta-analysis of individual participant data. Clin Gastroenterol Hepatol. 2015;13(3):440–51. e6.PubMedCrossRefGoogle Scholar
  87. 87.
    Koinuma M, Ohashi I, Hanafusa K, Shibuya H. Apparent diffusion coefficient measurements with diffusion-weighted magnetic resonance imaging for evaluation of hepatic fibrosis. J Magn Reson Imaging. 2005;22(1):80–5.PubMedCrossRefGoogle Scholar
  88. 88.
    Ichikawa T, Haradome H, Hachiya J, Nitatori T, Araki T. Diffusion-weighted MR imaging with a single-shot echoplanar sequence: detection and characterization of focal hepatic lesions. AJR Am J Roentgenol. 1998;170(2):397–402.PubMedCrossRefGoogle Scholar
  89. 89.
    Ichikawa T, Haradome H, Hachiya J, Nitatori T, Araki T. Diffusion-weighted MR imaging with single-shot echo-planar imaging in the upper abdomen: preliminary clinical experience in 61 patients. Abdom Imaging. 1999;24(5):456–61.PubMedCrossRefGoogle Scholar
  90. 90.
    Muller MF, Prasad P, Siewert B, Nissenbaum MA, Raptopoulos V, Edelman RR. Abdominal diffusion mapping with use of a whole-body echo-planar system. Radiology. 1994;190(2):475–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Namimoto T, Yamashita Y, Sumi S, Tang Y, Takahashi M. Focal liver masses: characterization with diffusion-weighted echo-planar MR imaging. Radiology. 1997;204(3):739–44.PubMedCrossRefGoogle Scholar
  92. 92.
    Taouli B, Vilgrain V, Dumont E, Daire JL, Fan B, Menu Y. Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients. Radiology. 2003;226(1):71–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Yamada I, Aung W, Himeno Y, Nakagawa T, Shibuya H. Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with intravoxel incoherent motion echo-planar MR imaging. Radiology. 1999;210(3):617–23.PubMedCrossRefGoogle Scholar
  94. 94.
    Poyraz AK, Onur MR, Kocakoc E, Ogur E. Diffusion-weighted MRI of fatty liver. J Magn Reson Imaging. 2012;35(5):1108–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Aisen AM, Doi K, Swanson SD. Detection of liver fibrosis with magnetic cross-relaxation. Magn Reson Med. 1994;31(5):551–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Alanen A, Komu M, Leino R, Toikkanen S. MR and magnetisation transfer imaging in cirrhotic and fatty livers. Acta Radiol. 1998;39(4):434–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Chen JH, Chai JW, Shen WC. Magnetization transfer contrast imaging of liver cirrhosis. Hepato-Gastroenterology. 1999;46(29):2872–7.PubMedGoogle Scholar
  98. 98.
    Lall CG, Aisen AM, Bansal N, Sandrasegaran K. Nonalcoholic fatty liver disease. AJR Am J Roentgenol. 2008;190(4):993–1002.PubMedCrossRefGoogle Scholar
  99. 99.
    Tsuda N, Okada M, Murakami T. Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Investig Radiol. 2007;42(4):242–7.CrossRefGoogle Scholar
  100. 100.
    Asanuma T, Ono M, Kubota K, Hirose A, Hayashi Y, Saibara T, et al. Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease. Gut. 2010;59(2):258–66.PubMedCrossRefGoogle Scholar
  101. 101.
    Beeman SC, Mandarino LJ, Georges JF, Bennett KM. Cationized ferritin as a magnetic resonance imaging probe to detect microstructural changes in a rat model of non-alcoholic steatohepatitis. Magn Reson Med. 2013;70(6):1728–38.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, et al. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003;100(18):10158–63.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Hu S, Chen AP, Zierhut ML, Bok R, Yen YF, Schroeder MA, et al. In vivo carbon-13 dynamic MRS and MRSI of normal and fasted rat liver with hyperpolarized 13C-pyruvate. Mol Imaging Biol. 2009;11(6):399–407.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Spielman DM, Mayer D, Yen YF, Tropp J, Hurd RE, Pfefferbaum A. In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate. Magn Reson Med. 2009;62(2):307–13.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Merritt ME, Harrison C, Sherry AD, Malloy CR, Burgess SC. Flux through hepatic pyruvate carboxylase and phosphoenolpyruvate carboxykinase detected by hyperpolarized 13C magnetic resonance. Proc Natl Acad Sci U S A. 2011;108(47):19084–9.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Lee P, Leong W, Tan T, Lim M, Han W, Radda GK. In vivo hyperpolarized carbon-13 magnetic resonance spectroscopy reveals increased pyruvate carboxylase flux in an insulin-resistant mouse model. Hepatology. 2013;57(2):515–24.PubMedCrossRefGoogle Scholar
  107. 107.
    Abele JT, Fung CI. Effect of hepatic steatosis on liver FDG uptake measured in mean standard uptake values. Radiology. 2010;254(3):917–24.PubMedCrossRefGoogle Scholar
  108. 108.
    Abikhzer G, Alabed YZ, Azoulay L, Assayag J, Rush C. Altered hepatic metabolic activity in patients with hepatic steatosis on FDG PET/CT. AJR Am J Roentgenol. 2011;196(1):176–80.PubMedCrossRefGoogle Scholar
  109. 109.
    Ceulemans G, Ilsen B, Verdries D, de Mey J, Everaert H. Focal eosinophilic hepatitis simulating a solitary metastatic lesion on FDG-PET/CT in a patient with history of head and neck cancer. JBR-BTR. 2011;94(2):94.PubMedGoogle Scholar
  110. 110.
    Nakahara T, Takagi Y, Takemasa K, Mitsui Y, Tsuyuki A, Shigematsu N, et al. Dose-related fluorodeoxyglucose uptake in acute radiation-induced hepatitis. Eur J Gastroenterol Hepatol. 2008;20(10):1040–4.PubMedCrossRefGoogle Scholar
  111. 111.
    Bural GG, Torigian DA, Burke A, Houseni M, Alkhawaldeh K, Cucchiara A, et al. Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept. Mol Imaging Biol. 2010;12(3):233–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Dostbil Z, Varoglu E, Serdengecti M, Kaya B, Onder H, Sari O. Evaluation of hepatic metabolic activity in non-alcoholic fatty livers on 18FDG PET/CT. Rev Esp Med Nucl Imagen Mol. 2013;32(3):156–61.PubMedGoogle Scholar
  113. 113.
    Hong SP, Noh TS, Moon SH, Cho YS, Lee EJ, Choi JY, et al. Hepatic glucose uptake is increased in association with elevated serum gamma-glutamyl transpeptidase and triglyceride. Dig Dis Sci. 2014;59(3):607–13.PubMedCrossRefGoogle Scholar
  114. 114.
    Moon SH, Hong SP, Cho YS, Noh TS, Choi JY, Kim BT, et al. Hepatic FDG uptake is associated with future cardiovascular events in asymptomatic individuals with non-alcoholic fatty liver disease. J Nucl Cardiol. 2015. doi: 10.1007/s12350-015-0297-y.
  115. 115.
    Iozzo P, Bucci M, Roivainen A, Nagren K, Jarvisalo MJ, Kiss J, et al. Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals. Gastroenterology. 2010;139(3):846–56, 56.e1–6.Google Scholar
  116. 116.
    Xie L, Yui J, Hatori A, Yamasaki T, Kumata K, Wakizaka H, et al. Translocator protein (18 kDa), a potential molecular imaging biomarker for non-invasively distinguishing non-alcoholic fatty liver disease. J Hepatol. 2012;57(5):1076–82.PubMedCrossRefGoogle Scholar
  117. 117.
    Lin J, Lu F, Zheng W, Xu S, Tai D, Yu H, et al. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique. J Biomed Opt. 2011;16(11):116024.PubMedCrossRefGoogle Scholar
  118. 118.
    Evers DJ, Westerkamp AC, Spliethoff JW, Pully VV, Hompes D, Hendriks BH, et al. Diffuse reflectance spectroscopy: toward real-time quantification of steatosis in liver. Transpl Int. 2015;28(4):465–74.PubMedCrossRefGoogle Scholar
  119. 119.
    Evers DJ, Nachabe R, Hompes D, van Coevorden F, Lucassen GW, Hendriks BH, et al. Optical sensing for tumor detection in the liver. Eur J Surg Oncol. 2013;39(1):68–75.PubMedCrossRefGoogle Scholar
  120. 120.
    Tian C, Xie Z, Fabiilli ML, Wang X. Imaging and sensing based on dual-pulse nonlinear photoacoustic contrast: a preliminary study on fatty liver. Opt Lett. 2015;40(10):2253–6.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Boursier J, de Ledinghen V, Sturm N, Amrani L, Bacq Y, Sandrini J, et al. Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C. J Gastroenterol. 2014;49(3):527–37.PubMedCrossRefGoogle Scholar
  122. 122.
    Hatta T, Fujinaga Y, Kadoya M, Ueda H, Murayama H, Kurozumi M, et al. Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease. J Gastroenterol. 2010;45(12):1263–71.PubMedCrossRefGoogle Scholar
  123. 123.
    Leiber LM, Boursier J, Michalak S, Roullier V, Fizanne L, Chaigneau J, et al. MRI versus histological methods for time course monitoring of steatosis amount in a murine model of NAFLD. Diagn Interv Imaging. 2015;96(9):915–22.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Mallinckrodt Institute of RadiologyWashington UniversitySt. LouisUSA
  2. 2.The Alvin J. Siteman Cancer CenterWashington UniversitySt. LouisUSA

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