La radiologia medica

, Volume 120, Issue 12, pp 1083–1093 | Cite as

Hepatic fat quantification using the proton density fat fraction (PDFF): utility of free-drawn-PDFF with a large coverage area

  • Kun Young Kim
  • Ji Soo SongEmail author
  • Stephan Kannengiesser
  • Young Min Han



To evaluate the diagnostic performance of magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) using a free-drawn region-of-interest (ROI) measurement of hepatic fat deposition compared to MR spectroscopy (MRS) as the reference standard.

Materials and methods

A total of 156 patients underwent 3T MR imaging with a multi-step adaptive fitting approach, multi-echo volume interpolated breath-hold examination (VIBE) acquisition and single-voxel high-speed T2-corrected multiple-echo 1H-MR spectroscopy (SVS). Seven ROI measurements were performed in each segment of the fat percentage maps (“segmental-PDFF”). Three ROIs were placed at the same level as the SVS (“VOI-PDFF”). Free-hand-drawn ROIs were placed at three different levels along the entire liver (“free-drawn-PDFF”) and separately along the right and left lobes (“free-drawn-PDFF-2”).


A strong correlation was found between VOI-PDFF and SVS (r = 0.977). The right lobe had greater fat content than the left lobe (p < 0.001). After image analysis, 54 and 46 patients were classified as having steatosis using SVS and free-drawn-PDFF as a reference standard, respectively. The diagnostic performance of free-drawn-PDFF was significantly different from SVS (p < 0.05).


Free-drawn-PDFF provides accurate and generalized information regarding hepatic fat deposition. It is a useful method, particularly if fat deposition is heterogeneous, and should be considered as a new reference standard.


Fat quantification Proton density fat fraction Hepatic steatosis MR spectroscopy 


Conflict of Interest

The authors declare that they have no conflict of interest.

Statement of human rights

For this type of study formal consent is not required.

Ethical standard

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40(6):1387–1395. doi: 10.1002/hep.20466 CrossRefPubMedGoogle Scholar
  2. 2.
    Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346(16):1221–1231. doi: 10.1056/NEJMra011775 CrossRefPubMedGoogle Scholar
  3. 3.
    Lewis JR, Mohanty SR (2010) Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci 55(3):560–578. doi: 10.1007/s10620-009-1081-0 CrossRefPubMedGoogle Scholar
  4. 4.
    Neuschwander-Tetri BA, Caldwell SH (2003) Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37(5):1202–1219. doi: 10.1053/jhep.2003.50193 CrossRefPubMedGoogle Scholar
  5. 5.
    Vuppalanchi R, Chalasani N (2009) Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology 49(1):306–317. doi: 10.1002/hep.22603 PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Mills SJ, Harrison SA (2005) Comparison of the natural history of alcoholic and nonalcoholic fatty liver disease. Curr Gastroenterol Rep 7(1):32–36CrossRefPubMedGoogle Scholar
  7. 7.
    Angulo P, Keach JC, Batts KP, Lindor KD (1999) Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30(6):1356–1362. doi: 10.1002/hep.510300604 CrossRefPubMedGoogle Scholar
  8. 8.
    Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ (1999) Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116(6):1413–1419CrossRefPubMedGoogle Scholar
  9. 9.
    Diehl AM (1997) Alcoholic liver disease: natural history. Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 3(3):206–211CrossRefGoogle Scholar
  10. 10.
    Tendler D, Lin S, Yancy WS Jr, Mavropoulos J, Sylvestre P, Rockey DC, Westman EC (2007) The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci 52(2):589–593. doi: 10.1007/s10620-006-9433-5 CrossRefPubMedGoogle Scholar
  11. 11.
    Musso G, Gambino R, Cassader M (2010) Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev 11(6):430–445. doi: 10.1111/j.1467-789X.2009.00657.x CrossRefPubMedGoogle Scholar
  12. 12.
    Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, Emick D, Lok AS, Conjeevaram HS (2005) One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 100(5):1072–1081. doi: 10.1111/j.1572-0241.2005.41334.x CrossRefPubMedGoogle Scholar
  13. 13.
    Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, Powell EE (2004) Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 53(3):413–419PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, Torimura T, Inuzuka S, Sata M, Tanikawa K (1997) Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 27(1):103–107CrossRefPubMedGoogle Scholar
  15. 15.
    Bravo AA, Sheth SG, Chopra S (2001) Liver biopsy. N Engl J Med 344(7):495–500. doi: 10.1056/NEJM200102153440706 CrossRefPubMedGoogle Scholar
  16. 16.
    Janiec DJ, Jacobson ER, Freeth A, Spaulding L, Blaszyk H (2005) Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies. Obes Surg 15(4):497–501. doi: 10.1381/0960892053723268 CrossRefPubMedGoogle Scholar
  17. 17.
    Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T, Group LS (2005) Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128(7):1898–1906CrossRefGoogle Scholar
  18. 18.
    Pilleul F, Chave G, Dumortier J, Scoazec JY, Valette PJ (2005) Fatty infiltration of the liver. Detection and grading using dual T1 gradient echo sequences on clinical MR system. Gastroenterol Clin Biol 29(11):1143–1147CrossRefPubMedGoogle Scholar
  19. 19.
    Reeder SB, Sirlin CB (2010) Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am 18(3):337–357. doi: 10.1016/j.mric.2010.08.013 PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288(2):E462–E468. doi: 10.1152/ajpendo.00064.2004 CrossRefPubMedGoogle Scholar
  21. 21.
    Cowin GJ, Jonsson JR, Bauer JD, Ash S, Ali A, Osland EJ, Purdie DM, Clouston AD, Powell EE, Galloway GJ (2008) Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging JMRI 28(4):937–945. doi: 10.1002/jmri.21542 CrossRefPubMedGoogle Scholar
  22. 22.
    Longo R, Pollesello P, Ricci C, Masutti F, Kvam BJ, Bercich L, Croce LS, Grigolato P, Paoletti S, de Bernard B et al (1995) Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J Magn Reson Imaging JMRI 5(3):281–285CrossRefPubMedGoogle Scholar
  23. 23.
    Yokoo T, Bydder M, Hamilton G, Middleton MS, Gamst AC, Wolfson T, Hassanein T, Patton HM, Lavine JE, Schwimmer JB, Sirlin CB (2009) Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T. Radiology 251(1):67–76. doi: 10.1148/radiol.2511080666 PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Reeder SB, Cruite I, Hamilton G, Sirlin CB (2011) Quantitative assessment of Liver Fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging 34(4):729–749. doi: 10.1002/jmri.22775 CrossRefPubMedGoogle Scholar
  25. 25.
    Bydder M, Yokoo T, Hamilton G, Middleton MS, Chavez AD, Schwimmer JB, Lavine JE, Sirlin CB (2008) Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging 26(3):347–359. doi: 10.1016/j.mri.2007.08.012 PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Bashir MR, Zhong X, Nickel MD, Fananapazir G, Kannengiesser SA, Kiefer B, Dale BM (2015) Quantification of hepatic steatosis with a multistep adaptive fitting MRI approach: prospective validation against MR spectroscopy. AJR Am J Roentgenol 204(2):297–306. doi: 10.2214/AJR.14.12457 CrossRefPubMedGoogle Scholar
  27. 27.
    Kim H, Taksali SE, Dufour S, Befroy D, Goodman TR, Petersen KF, Shulman GI, Caprio S, Constable RT (2008) Comparative MR study of hepatic fat quantification using single-voxel proton spectroscopy, two-point dixon and three-point IDEAL. Magn Reson Med 59(3):521–527. doi: 10.1002/mrm.21561 PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Tang A, Tan J, Sun M, Hamilton G, Bydder M, Wolfson T, Gamst AC, Middleton M, Brunt EM, Loomba R, Lavine JE, Schwimmer JB, Sirlin CB (2013) Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology 267(2):422–431. doi: 10.1148/radiol.12120896 PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Joshi AA, Hu HH, Leahy RM, Goran MI, Nayak KS (2013) Automatic intra-subject registration-based segmentation of abdominal fat from water-fat MRI. J Magn Reson Imaging JMRI 37(2):423–430. doi: 10.1002/jmri.23813 CrossRefPubMedGoogle Scholar
  30. 30.
    Idilman IS, Aniktar H, Idilman R, Kabacam G, Savas B, Elhan A, Celik A, Bahar K, Karcaaltincaba M (2013) Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology 267(3):767–775. doi: 10.1148/radiol.13121360 CrossRefPubMedGoogle Scholar
  31. 31.
    Zhong X, Nickel MD, Kannengiesser SA, Dale BM, Kiefer B, Bashir MR (2013) Liver fat quantification using a multi-step adaptive fitting approach with multi-echo GRE imaging. Magn Reson Medicine. doi: 10.1002/mrm.25054 Google Scholar
  32. 32.
    Noureddin M, Lam J, Peterson MR, Middleton M, Hamilton G, Le TA, Bettencourt R, Changchien C, Brenner DA, Sirlin C, Loomba R (2013) Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 58(6):1930–1940. doi: 10.1002/hep.26455 CrossRefPubMedGoogle Scholar
  33. 33.
    Ligabue G, Besutti G, Scaglioni R, Stentarelli C, Guaraldi G (2013) MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends. Quant Imaging Med Surg 3(4):192–195. doi: 10.3978/j.issn.2223-4292.2013.08.01 PubMedCentralPubMedGoogle Scholar
  34. 34.
    Capitan V, Petit JM, Aho S, Lefevre PH, Favelier S, Loffroy R, Hillon P, Krause D, Cercueil JP, Guiu B (2012) Macroscopic heterogeneity of liver fat: an MR-based study in type-2 diabetic patients. Eur Radiol 22(10):2161–2168. doi: 10.1007/s00330-012-2468-4 CrossRefPubMedGoogle Scholar
  35. 35.
    Bonekamp S, Tang A, Mashhood A, Wolfson T, Changchien C, Middleton MS, Clark L, Gamst A, Loomba R, Sirlin CB (2014) Spatial distribution of MRI-Determined hepatic proton density fat fraction in adults with nonalcoholic fatty liver disease. J Magn Reson Imaging JMRI 39(6):1525–1532CrossRefPubMedGoogle Scholar
  36. 36.
    Pineda N, Sharma P, Xu Q, Hu X, Vos M, Martin DR (2009) Measurement of hepatic lipid: high-speed T2-corrected multiecho acquisition at 1H MR spectroscopy–a rapid and accurate technique. Radiology 252(2):568–576. doi: 10.1148/radiol.2523082084 CrossRefPubMedGoogle Scholar
  37. 37.
    Wieckowska A, McCullough AJ, Feldstein AE (2007) Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 46(2):582–589. doi: 10.1002/hep.21768 CrossRefPubMedGoogle Scholar
  38. 38.
    Brunt EM, Tiniakos DG (2010) Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol WJG 16(42):5286–5296CrossRefPubMedGoogle Scholar
  39. 39.
    Yoshimitsu K, Honda H, Kuroiwa T, Irie H, Aibe H, Shinozaki K, Masuda K (2001) Unusual hemodynamics and pseudolesions of the noncirrhotic liver at CT. Radiographics 21:S81–S96Google Scholar
  40. 40.
    Joe E, Lee JM, Kim KW, Lee KB, Kim SJ, Baek JH, Shin CI, Suh KS, Yi NJ, Han JK, Choi BI (2012) Quantification of hepatic macrosteatosis in living, related liver donors using T1-independent, T2*-corrected chemical shift MRI. J Magn Reson Imag JMRI 36(5):1124–1130. doi: 10.1002/jmri.23738 CrossRefGoogle Scholar

Copyright information

© Italian Society of Medical Radiology 2015

Authors and Affiliations

  • Kun Young Kim
    • 1
  • Ji Soo Song
    • 1
    Email author
  • Stephan Kannengiesser
    • 2
  • Young Min Han
    • 1
  1. 1.Department of Radiology, Chonbuk National University Medical School and HospitalResearch Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University HospitalJeonju-SiKorea
  2. 2.MR Applications DevelopmentSiemens HealthcareErlangenGermany

Personalised recommendations