Hepatic Steatosis: Quantification by Proton Density Fat Fraction with MR Imaging versus Liver Biopsy

Published Online:https://doi.org/10.1148/radiol.13121360

Proton density fat fraction provides an accurate estimation of the presence and grading of hepatic steatosis between nonexistent or mild and moderate or severe forms in patients with nonalcoholic fatty liver disease.

Purpose

To determine utility of proton density fat fraction (PDFF) measurements for quantifying the liver fat content in patients with nonalcoholic fatty liver disease (NAFLD), and compare these results with liver biopsy findings.

Materials and Methods

This retrospective study was approved by the institutional review board with waivers of informed consent. Between June 2010 and April 2011, 86 patients received a diagnosis of NAFLD. Ten patients did not accept liver biopsy and six patients had contraindications for magnetic resonance (MR) imaging. Seventy patients were included in this study. Seventy patients with NAFLD (40 men, 30 women; mean age, 44.7 years; range, 16–69 years) underwent T1-independent volumetric multiecho gradient-echo imaging with T2* correction and spectral fat modeling. Median time interval between MR imaging and liver biopsy was 14.5 days (range, 0–259 days). MR examinations were performed with a 1.5-T MR imaging system. Complex-based PDFF measurements were performed by placing regions of interest in Couinaud system segments V–VI and all liver segments from I to VIII. All liver biopsy specimens were retrieved from archives and evaluated by one pathologist for hepatic steatosis according to criteria from a previous study. Pearson correlation coefficient, receiver operating characteristics, and linear regression analyses were used for statistical analyses.

Results

Mean PDFF calculated with MR imaging was 18.1% ± 9.5 (standard deviation). Close correlation for quantification of hepatic steatosis was observed between PDFF and liver biopsy (r = 0.82). PDFF was effective in discriminating moderate or severe hepatic steatosis from mild or no hepatic steatosis, with area under the curve of 0.95. The correlation between biopsy and PDFF-determined steatosis was less pronounced when fibrosis was present (r = 0.60) than when fibrosis was absent (r = 0.86; P = .02).

Conclusion

PDFF measurement by MR imaging provided a noninvasive, accurate estimation of the presence and grading of hepatic steatosis in patients with NAFLD. Hepatic fibrosis reduced the correlation between biopsy results and PDFF.

© RSNA, 2013

References

  • 1 Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346(16):1221–1231.
  • 2 Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 2003;37(5):1202–1219.
  • 3 Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2009;49(1):306–317.
  • 4 Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci 2010;55(3):560–578.
  • 5 Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics 2006;118(4):1388–1393.
  • 6 Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008;28(4):339–350.
  • 7 Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 2009;13(4):511–531.
  • 8 Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009;58(11):1538–1544.
  • 9 Marchesini G, Bugianesi E, Forlani G, et al.. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37(4):917–923.
  • 10 Pagano G, Pacini G, Musso G, et al.. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology 2002;35(2):367–372.
  • 11 Brea A, Mosquera D, Martín E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol 2005;25(5):1045–1050.
  • 12 Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology 1995;22(6):1714–1719.
  • 13 Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 2008;28(4):370–379.
  • 14 Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001;344(7):495–500.
  • 15 Ratziu V, Charlotte F, Heurtier A, et al.. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128(7):1898–1906.
  • 16 Saadeh S, Younossi ZM, Remer EM, et al.. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123(3):745–750.
  • 17 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):433–445.
  • 18 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):507–511.
  • 19 Pilleul F, Chave G, Dumortier J, Scoazec JY, Valette PJ. Fatty infiltration of the liver. Detection and grading using dual T1 gradient echo sequences on clinical MR system. Gastroenterol Clin Biol 2005;29(11):1143–1147.
  • 20 Reeder SB, Sirlin CB. Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am 2010;18(3):337–357, ix.
  • 21 Longo R, Pollesello P, Ricci C, et al.. Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J Magn Reson Imaging 1995;5(3):281–285.
  • 22 Szczepaniak LS, Nurenberg P, Leonard D, 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(2):E462–E468.
  • 23 Cowin GJ, Jonsson JR, Bauer JD, et al.. Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging 2008;28(4):937–945.
  • 24 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):729–749.
  • 25 Reeder SB, Robson PM, Yu H, et al.. Quantification of hepatic steatosis with MRI: the effects of accurate fat spectral modeling. J Magn Reson Imaging 2009;29(6):1332–1339.
  • 26 Yokoo T, Bydder M, Hamilton G, 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.
  • 27 Kim H, Taksali SE, Dufour S, 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):521–527.
  • 28 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(9):2467–2474.
  • 29 Kleiner DE, Brunt EM, Van Natta ML, et al.. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–1321.
  • 30 World Health Organization. Report of a WHO consultation: definition of metabolic syndrome in definition, diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization, Department of Noncommunicable Disease Surveillance, 1999.
  • 31 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28(7):412–419.
  • 32 Yu H, McKenzie CA, Shimakawa A, et al.. Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. J Magn Reson Imaging 2007;26(4):1153–1161.
  • 33 Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143(1):29–36.
  • 34 McPherson S, Jonsson JR, Cowin GJ, et al.. Magnetic resonance imaging and spectroscopy accurately estimate the severity of steato sis provided the stage of fibrosis is considered. J Hepatol 2009;51(2):389–397.
  • 35 Kalra N, Duseja A, Das A, et al.. Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). Ann Hepatol 2009;8(1):21–25.
  • 36 Friedrich-Rust M, Müller C, Winckler A, et al.. Assessment of liver fibrosis and steatosis in PBC with FibroScan, MRI, MR-spectroscopy, and serum markers. J Clin Gastroenterol 2010;44(1):58–65.
  • 37 Karcaaltincaba M, Akhan O. Imaging of hepatic steatosis and fatty sparing. Eur J Radiol 2007;61(1):33–43.
  • 38 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):1122–1134.
  • 39 Hines CD, Agni R, Roen C, et al.. Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse. J Magn Reson Imaging 2012;35(4):844–851.
  • 40 Hines CD, Yu H, Shimakawa A, McKenzie CA, Brittain JH, Reeder SB. T1 independent, T2* corrected MRI with accurate spectral modeling for quantification of fat: validation in a fat-water-SPIO phantom. J Magn Reson Imaging 2009;30(5):1215–1222.
  • 41 Karçaaltincaba M, Idilman I, Celik A. Focal sparing of iron and fat in liver tissue in patients with hemosiderosis: diagnosis with combination of R2* relaxometry and proton density fat fraction calculation by MRI. Diagn Interv Radiol 2011;17(4):323–327.
  • 42 Bydder M, Shiehmorteza M, Yokoo T, et al.. Assessment of liver fat quantification in the presence of iron. Magn Reson Imaging 2010;28(6):767–776.
  • 43 Hussain HK, Chenevert TL, Londy FJ, et al.. Hepatic fat fraction: MR imaging for quantitative measurement and display—early experience. Radiology 2005;237(3):1048–1055.
  • 44 Westphalen AC, Qayyum A, Yeh BM, et al.. Liver fat: effect of hepatic iron deposition on evaluation with opposed-phase MR imaging. Radiology 2007;242(2):450–455.
  • 45 Kang GH, Cruite I, Shiehmorteza M, et al.. Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms. J Magn Reson Imaging 2011;34(4):928–934.

Article History

Received June 19, 2012; revision requested August 24; revision received October 2; accepted October 31; final version accepted November 13.
Published online: June 2013
Published in print: June 2013