Abstract
Excessive intracellular accumulation of triglycerides in the liver, or hepatic steatosis, is a highly prevalent condition affecting approximately one billion people worldwide. In the absence of secondary cause, the term nonalcoholic fatty liver disease (NAFLD) is used. Hepatic steatosis may progress into nonalcoholic steatohepatitis, the more aggressive form of NAFLD, associated with hepatic complications such as fibrosis, liver failure and hepatocellular carcinoma. Hepatic steatosis is associated with metabolic syndrome, cardiovascular disease and represents an independent risk factor for type 2 diabetes, cardiovascular disease and malignancy. Percutaneous liver biopsy is the current reference standard for NAFLD assessment; however, it is an invasive procedure associated with complications and suffers from high sampling variability, impractical for clinical routine and drug efficiency studies. Therefore, noninvasive imaging methods are increasingly used for the diagnosis and monitoring of NAFLD. Among the methods quantifying liver fat, chemical-shift-encoded MRI (CSE-MRI)-based proton density fat-fraction (PDFF) has shown the most promise. MRI-PDFF is increasingly accepted as quantitative imaging biomarker of liver fat that is transforming daily clinical practice and influencing the development of new treatments for NAFLD. Furthermore, CT is an important imaging method for detection of incidental steatosis, and the practical advantages of quantitative ultrasound hold great promise for the future. Understanding the disease burden of NAFLD and the role of imaging may initiate important interventions aimed at avoiding the hepatic and extrahepatic complications of NAFLD. This article reviews clinical burden of NAFLD, and the role of noninvasive imaging techniques for quantification of liver fat.
Similar content being viewed by others
References
Byrne CD, Targher G (2015) NAFLD: A multisystem disease. Journal of Hepatology 62:S47–S64. https://doi.org/10.1016/j.jhep.2014.12.012
Estes C, Razavi H, Loomba R, et al (2018) Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease: Estes et al. Hepatology 67:123–133. https://doi.org/10.1002/hep.29466
Perumpail BJ, Khan MA, Yoo ER, et al (2017) Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. WJG 23:8263–8276. https://doi.org/10.3748/wjg.v23.i47.8263
Chalasani N, Younossi Z, Lavine JE, et al (2018) The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases. 67:30
Adinolfi L (2001) Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology 33:1358–1364. https://doi.org/10.1053/jhep.2001.24432
Donohue, Jr TM (2007) Alcohol-induced steatosis in liver cells. World J Gastroenterol 13:4974–4978
Nassir F, Rector RS, Hammoud GM, Ibdah JA (2015) Pathogenesis and Prevention of Hepatic Steatosis. Gastroenterology & Hepatology 11:167–175
Benedict M, Zhang X (2017) Non-alcoholic fatty liver disease: An expanded review. WJH 9:715. https://doi.org/10.4254/wjh.v9.i16.715
Gluchowski NL, Becuwe M, Walther TC, Farese RV (2017) Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol 14:343–355. https://doi.org/10.1038/nrgastro.2017.32
Mantovani A, Byrne CD, Bonora E, Targher G (2018) Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta-analysis. Dia Care 41:372–382. https://doi.org/10.2337/dc17-1902
Adams LA, Anstee QM, Tilg H, Targher G (2017) Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66:1138–1153. https://doi.org/10.1136/gutjnl-2017-313884
Puchner SB, Lu MT, Mayrhofer T, et al (2015) High-Risk Coronary Plaque at Coronary CT Angiography Is Associated with Nonalcoholic Fatty Liver Disease, Independent of Coronary Plaque and Stenosis Burden: Results from the ROMICAT II Trial. Radiology 274:693–701. https://doi.org/10.1148/radiol.14140933
Caussy C, Reeder SB, Sirlin CB, Loomba R (2018) Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials. Hepatology 68:763–772. https://doi.org/10.1002/hep.29797
Cairns SR, Peters TJ (1983) Biochemical Analysis of Hepatic Lipid in Alcoholic and Diabetic and Control Subjects. Clinical Science 65:645–652. https://doi.org/10.1042/cs0650645
Ludwig J, Viggiano T, McGill D, Oh B (1980) Nonalcoholic steatohepatitis: mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 7:434–8
Brunt EM, Janney CG, Bisceglie AM, et al (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterology 94:2467–2474. https://doi.org/10.1111/j.1572-0241.1999.01377.x
Wesolowski SR, Kasmi KCE, Jonscher KR, Friedman JE (2017) Developmental origins of NAFLD: a womb with a clue. Nat Rev Gastroenterol Hepatol 14:81–96. https://doi.org/10.1038/nrgastro.2016.160
Nobili V, Alisi A, Valenti L, et al (2019) NAFLD in children: new genes, new diagnostic modalities and new drugs. Nat Rev Gastroenterol Hepatol 16:517–530. https://doi.org/10.1038/s41575-019-0169-z
Wilkins T, Tadkod A, Hepburn I, Schade RR (2013) Nonalcoholic Fatty Liver Disease: Diagnosis and Management. Nonalcoholic Fatty Liver Disease 88:8
Reeder SB, Sirlin CB (2010) Quantification of Liver Fat with Magnetic Resonance Imaging. Magnetic Resonance Imaging Clinics of North America 18:337–357. https://doi.org/10.1016/j.mric.2010.08.013
Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P (2018) Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci 75:3313–3327. https://doi.org/10.1007/s00018-018-2860-6
Targher G, Byrne CD (2017) Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nature Reviews Nephrology 5:297–310. https://doi.org/10.1038/nrneph.2017.16
Rinella ME (2015) Nonalcoholic Fatty Liver Disease: A Systematic Review. JAMA 313:2263. https://doi.org/10.1001/jama.2015.5370
Pembroke T, Deschenes M, Lebouché B, et al (2017) Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis. Journal of Hepatology 67:801–808. https://doi.org/10.1016/j.jhep.2017.05.011
Boyd A, Cain O, Chauhan A, Webb GJ (2020) Medical liver biopsy: background, indications, procedure and histopathology. Frontline Gastroenterol 11:40–47. https://doi.org/10.1136/flgastro-2018-101139
Jayakumar S, Middleton MS, Lawitz EJ, et al (2019) Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib. Journal of Hepatology 70:133–141. https://doi.org/10.1016/j.jhep.2018.09.024
Younossi ZM, Loomba R, Anstee QM, et al (2018) Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 68:349–360. https://doi.org/10.1002/hep.29721
Bedogni G, Nobili V, Tiribelli C (2014) Epidemiology of fatty liver: An update. World J Gastroenterol 20:9050–9054. https://doi.org/10.3748/wjg.v20.i27.9050
Tapper EB, Lok AS-F (2017) Use of Liver Imaging and Biopsy in Clinical Practice. N Engl J Med 377:756–768. https://doi.org/10.1056/NEJMra1610570
Ozcan HN, Oguz B, Haliloglu M, et al (2015) Imaging patterns of fatty liver in pediatric patients. Diagn Interv Radiol 21:355–360. https://doi.org/10.5152/dir.2015.14505
Poynard T, Lenaour G, Vaillant JC, et al (2012) Liver Biopsy Analysis Has a Low Level of Performance for Diagnosis of Intermediate Stages of Fibrosis. Clinical Gastroenterology and Hepatology 10:657-663.e7. https://doi.org/10.1016/j.cgh.2012.01.023
Ratziu V, Charlotte F, Heurtier A, et al (2005) Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease. Gastroenterology 128:1898–1906. https://doi.org/10.1053/j.gastro.2005.03.084
Zhang YN, Fowler KJ, Hamilton G, et al (2018) Liver fat imaging—a clinical overview of ultrasound, CT, and MR imaging. BJR 20170959. https://doi.org/10.1259/bjr.20170959
Ozturk A, Grajo JR, Gee MS, et al (2018) Quantitative Hepatic Fat Quantification in Non-alcoholic Fatty Liver Disease Using Ultrasound-Based Techniques: A Review of Literature and Their Diagnostic Performance. Ultrasound in Medicine & Biology 44:2461–2475. https://doi.org/10.1016/j.ultrasmedbio.2018.07.019
Paige JS, Bernstein GS, Heba E, et al (2017) A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease. American Journal of Roentgenology 208:W168–W177. https://doi.org/10.2214/AJR.16.16726
Park CC, Nguyen P, Hernandez C, et al (2017) Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology 152:598-607.e2. https://doi.org/10.1053/j.gastro.2016.10.026
Karlas T, Petroff D, Garnov N, et al (2014) Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR Spectroscopy. PLoS ONE 9:e91987. https://doi.org/10.1371/journal.pone.0091987
Imajo K, Kessoku T, Honda Y, et al (2016) Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastography. Gastroenterology 150:626-637.e7. https://doi.org/10.1053/j.gastro.2015.11.048
Guiu B (2013) Other Diffuse Liver Diseases: Steatosis, Hemochromatosis, etc. In: Hamm B, Ros PR (eds) Abdominal Imaging. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 1027–1044
Hamer OW, Aguirre DA, Casola G, et al (2006) Fatty Liver: Imaging Patterns and Pitfalls. RadioGraphics 26:1637–1653. https://doi.org/10.1148/rg.266065004
Pickhardt PJ, Graffy PM, Reeder SB, et al (2018) Quantification of Liver Fat Content with Unenhanced MDCT: Phantom and Clinical Correlation with MRI Proton Density Fat Fraction. American Journal of Roentgenology 211:W151–W157. https://doi.org/10.2214/AJR.17.19391
Pickhardt PJ, Graffy PM, Zea R, et al (2020) Automated CT biomarkers for opportunistic prediction of future cardiovascular events and mortality in an asymptomatic screening population: a retrospective cohort study. The Lancet Digital Health 2:e192–e200. https://doi.org/10.1016/S2589-7500(20)30025-X
Kramer H, Pickhardt PJ, Kliewer MA, et al (2017) Accuracy of Liver Fat Quantification With Advanced CT, MRI, and Ultrasound Techniques: Prospective Comparison With MR Spectroscopy. American Journal of Roentgenology 208:92–100. https://doi.org/10.2214/AJR.16.16565
Hahn L, Reeder SB, del Rio AM, Pickhardt PJ (2015) Longitudinal Changes in Liver Fat Content in Asymptomatic Adults: Hepatic Attenuation on Unenhanced CT as an Imaging Biomarker for Steatosis. American Journal of Roentgenology 205:1167–1172. https://doi.org/10.2214/AJR.15.14724
Kodama Y, Ng CS, Wu TT, et al (2007) Comparison of CT Methods for Determining the Fat Content of the Liver. American Journal of Roentgenology 188:1307–1312. https://doi.org/10.2214/AJR.06.0992
Li Q, Dhyani M, Grajo JR, et al (2018) Current status of imaging in nonalcoholic fatty liver disease. WJH 10:530–542. https://doi.org/10.4254/wjh.v10.i8.530
Lee SS, Park SH, Kim HJ, et al (2010) Non-invasive assessment of hepatic steatosis: Prospective comparison of the accuracy of imaging examinations. Journal of Hepatology 52:579–585. https://doi.org/10.1016/j.jhep.2010.01.008
Wells MM, Li Z, Addeman B, et al (2016) Computed Tomography Measurement of Hepatic Steatosis: Prevalence of Hepatic Steatosis in a Canadian Population. Canadian Journal of Gastroenterology and Hepatology 2016:1–7. https://doi.org/10.1155/2016/4930987
Fazel R, Krumholz HM, Wang Y, et al (2009) Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures. N Engl J Med 361:849–857. https://doi.org/10.1056/NEJMoa0901249
Patrick D, White FE, Adams PC (1984) Long-term amiodarone therapy: a cause of increased hepatic attenuation on CT. BJR 57:573–576. https://doi.org/10.1259/0007-1285-57-679-573
Cheng X, Blake GM, Brown JK, et al (2017) The measurement of liver fat from single-energy quantitative computed tomography scans. Quant Imaging Med Surg 7:281–291. https://doi.org/10.21037/qims.2017.05.06
Lee SS (2014) Radiologic evaluation of nonalcoholic fatty liver disease. WJG 20:7392. https://doi.org/10.3748/wjg.v20.i23.7392
Chen X, Ma T, Yip R, et al (2020) Elevated prevalence of moderate-to-severe hepatic steatosis in World Trade Center General Responder Cohort in a program of CT lung screening. Clinical Imaging 60:237–243. https://doi.org/10.1016/j.clinimag.2019.12.009
Reeder SB, Cruite I, Hamilton G, Sirlin CB (2011) Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging 34:729–749. https://doi.org/10.1002/jmri.22580
Yokoo T, Serai SD, Pirasteh A, et al (2018) Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis. Radiology 286:486–498. https://doi.org/10.1148/radiol.2017170550
Reeder SB, Hu HH, Sirlin CB (2012) Proton density fat-fraction: A standardized mr-based biomarker of tissue fat concentration. J Magn Reson Imaging 36:1011–1014. https://doi.org/10.1002/jmri.23741
Tang A, Tan J, Sun M, et al (2013) Nonalcoholic Fatty Liver Disease: MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis. Radiology 267:422–431. https://doi.org/10.1148/radiol.12120896
Tang A, Desai A, Hamilton G, et al (2015) Accuracy of MR Imaging–estimated Proton Density Fat Fraction for Classification of Dichotomized Histologic Steatosis Grades in Nonalcoholic Fatty Liver Disease. Radiology 274:416–425. https://doi.org/10.1148/radiol.14140754
Middleton MS, Van Natta ML, Heba ER, et al (2018) Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat fraction in pediatric nonalcoholic fatty liver disease: Middleton et al. Hepatology 67:858–872. https://doi.org/10.1002/hep.29596
Middleton MS, Heba ER, Hooker CA, et al (2017) Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis. Gastroenterology 153:753–761. https://doi.org/10.1053/j.gastro.2017.06.005
Kukuk GM, Hittatiya K, Sprinkart AM, et al (2015) Comparison between modified Dixon MRI techniques, MR spectroscopic relaxometry, and different histologic quantification methods in the assessment of hepatic steatosis. Eur Radiol 25:2869–2879. https://doi.org/10.1007/s00330-015-3703-6
QIBA PDFF Biomarker Comitee. In: PDFF Biomarker Comitee. http://qibawiki.rsna.org/index.php/PDFF_Biomarker_Ctte
Hamilton G, Yokoo T, Bydder M, et al (2011) In vivo characterization of the liver fat 1 H MR spectrum: IN VIVO CHARACTERIZATION OF THE LIVER FAT 1 H MR SPECTRUM. NMR Biomed 24:784–790. https://doi.org/10.1002/nbm.1622
Hamilton G, Middleton MS, Bydder M, et al (2009) Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification. J Magn Reson Imaging 30:145–152. https://doi.org/10.1002/jmri.21809Hamilton G, Middleton MS, Bydder M, et al (2009) Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification. J Magn Reson Imaging 30:145–152. https://doi.org/10.1002/jmri.21809
Kühn J-P, Hernando D, Mensel B, et al (2014) Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis: Quantitative Chemical Shift-Encoded MRI. J Magn Reson Imaging 39:1494–1501. https://doi.org/10.1002/jmri.24289
Bohte AE, van Werven JR, Bipat S, Stoker J (2011) The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol 21:87–97. https://doi.org/10.1007/s00330-010-1905-5
Liu C-Y, McKenzie CA, Yu H, et al (2007) Fat quantification with IDEAL gradient echo imaging: Correction of bias fromT1 and noise. Magn Reson Med 58:354–364. https://doi.org/10.1002/mrm.21301
Yu H, McKenzie CA, Shimakawa A, et al (2007) Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. J Magn Reson Imaging 26:1153–1161. https://doi.org/10.1002/jmri.21090
Yu H, Shimakawa A, McKenzie CA, et al (2008) Multiecho water-fat separation and simultaneous R 2* estimation with multifrequency fat spectrum modeling. Magn Reson Med 60:1122–1134. https://doi.org/10.1002/mrm.21737
Bydder M, Yokoo T, Hamilton G, et al (2008) Relaxation effects in the quantification of fat using gradient echo imaging. Magnetic Resonance Imaging 26:347–359. https://doi.org/10.1016/j.mri.2007.08.012
Hernando D, Hines CDG, Yu H, Reeder SB (2012) Addressing phase errors in fat-water imaging using a mixed magnitude/complex fitting method. Magn Reson Med 67:638–644. https://doi.org/10.1002/mrm.23044
Yu H, Shimakawa A, Hines CDG, et al (2011) Combination of complex-based and magnitude-based multiecho water-fat separation for accurate quantification of fat-fraction. Magn Reson Med 66:199–206. https://doi.org/10.1002/mrm.22840
Hernando D, Sharma SD, Kramer H, Reeder SB (2014) On the confounding effect of temperature on chemical shift-encoded fat quantification: Effect of Temperature on CSE Fat Quantification. Magn Reson Med 72:464–470. https://doi.org/10.1002/mrm.24951
Hernando D, Haldar JP, Sutton BP, et al (2008) Joint estimation of water/fat images and field inhomogeneity map. Magn Reson Med 59:571–580. https://doi.org/10.1002/mrm.21522
Hernando D, Liang Z-P, Kellman P (2010) Chemical shift-based water/fat separation: A comparison of signal models. Magn Reson Med 64:811–822. https://doi.org/10.1002/mrm.22455
Hines CDG, Yu H, Shimakawa A, et al (2009) T1 Independent, T2* Corrected MRI with Accurate Spectral Modeling for Quantification of Fat: Validation in a Fat-Water-SPIO Phantom. J Magn Reson Imaging 30:1215–1222. https://doi.org/10.1002/jmri.21957
Hernando D, Sharma SD, Aliyari Ghasabeh M, et al (2017) Multisite, multivendor validation of the accuracy and reproducibility of proton-density fat-fraction quantification at 1.5T and 3T using a fat-water phantom: Proton-Density Fat-Fraction Quantification at 1.5T and 3T. Magn Reson Med 77:1516–1524. https://doi.org/10.1002/mrm.26228
Hines CDG, Agni R, Roen C, et al (2012) Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse. J Magn Reson Imaging 35:844–851. https://doi.org/10.1002/jmri.22890
Hines CDG, Yu H, Shimakawa A, et al (2010) Quantification of Hepatic Steatosis with 3-T MR Imaging: Validation in ob/ob Mice. Radiology 254:119–128. https://doi.org/10.1148/radiol.09090131
Bannas P, Kramer H, Hernando D, et al (2015) Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers: STEATOHEPATITIS/METABOLIC LIVER DISEASE. Hepatology 62:1444–1455. https://doi.org/10.1002/hep.28012
Idilman IS, Aniktar H, Idilman R, et al (2013) Hepatic Steatosis: Quantification by Proton Density Fat Fraction with MR Imaging versus Liver Biopsy. Radiology 267:767–775. https://doi.org/10.1148/radiol.13121360
Permutt Z, Le T-A, Peterson MR, et al (2012) Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther 36:22–29. https://doi.org/10.1111/j.1365-2036.2012.05121.x
Idilman IS, Keskin O, Celik A, et al (2016) A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease. Acta Radiol 57:271–278. https://doi.org/10.1177/0284185115580488
Bashir MR, Zhong X, Nickel MD, et al (2015) Quantification of Hepatic Steatosis With a Multistep Adaptive Fitting MRI Approach: Prospective Validation Against MR Spectroscopy. American Journal of Roentgenology 204:297–306. https://doi.org/10.2214/AJR.14.12457
Meisamy S, Hines CDG, Hamilton G, et al (2011) Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy. Radiology 258:767–775. https://doi.org/10.1148/radiol.10100708
Pooler BD, Hernando D, Ruby JA, et al (2018) Validation of a motion-robust 2D sequential technique for quantification of hepatic proton density fat fraction during free breathing: Hepatic PDFF During Free Breathing. J Magn Reson Imaging 48:1578–1585. https://doi.org/10.1002/jmri.26056
Hernando D, Levin YS, Sirlin CB, Reeder SB (2014) Quantification of liver iron with MRI: State of the art and remaining challenges: Liver Iron Quantification Using MRI. J Magn Reson Imaging 40:1003–1021. https://doi.org/10.1002/jmri.24584
Campo CA, Hernando D, Schubert T, et al (2017) Standardized Approach for ROI-Based Measurements of Proton Density Fat Fraction and R2* in the Liver. American Journal of Roentgenology 209:592–603. https://doi.org/10.2214/AJR.17.17812
Stocker D, Bashir MR, Kannengiesser SAR, Reiner CS (2018) Accuracy of Automated Liver Contouring, Fat Fraction, and R2* Measurement on Gradient Multiecho Magnetic Resonance Images: Journal of Computer Assisted Tomography 42:697–706. https://doi.org/10.1097/RCT.0000000000000759
Wang K, Mamidipalli A, Retson T, et al (2019) Automated CT and MRI Liver Segmentation and Biometry Using a Generalized Convolutional Neural Network. Radiology: Artificial Intelligence 1:180022. https://doi.org/10.1148/ryai.2019180022
Roberts NT, Hernando D, Holmes JH, et al (2018) Noise properties of proton density fat fraction estimated using chemical shift-encoded MRI: Noise Properties of PDFF. Magn Reson Med 80:685–695. https://doi.org/10.1002/mrm.27065
Raunig DL, McShane LM, Pennello G, et al (2015) Quantitative imaging biomarkers: A review of statistical methods for technical performance assessment. Stat Methods Med Res 24:27–67. https://doi.org/10.1177/0962280214537344
Noureddin M, Lam J, Peterson MR, et al (2013) Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials: Hepatology. Hepatology 58:1930–1940. https://doi.org/10.1002/hep.26455
Kim B, Kim SY, Kim KW, et al (2018) MRI in donor candidates for living donor liver transplant: Technical and practical considerations: Living Donor Liver Transplant. J Magn Reson Imaging 48:1453–1467. https://doi.org/10.1002/jmri.26257
Parente DB, Rodrigues RS, Paiva FF, et al (2014) Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of Fatty Liver in Diabetic Patients in Clinical Practice? PLoS ONE 9:e112574. https://doi.org/10.1371/journal.pone.0112574
Kleiner DE, Brunt EM, Ferrell LD, et al (2005) Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease. 41:9
Le T-A, Chen J, Changchien C, et al (2012) Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial. Hepatology 56:922–932. https://doi.org/10.1002/hep.25731
Cui J, Philo L, Nguyen P, et al (2016) Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial. Journal of Hepatology 65:369–376. https://doi.org/10.1016/j.jhep.2016.04.021
Loomba R, Sirlin CB, Ang B, et al (2015) Ezetimibe for the treatment of nonalcoholic steatohepatitis: Assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial): Steatohepatitis/Metabolic Liver Disease. Hepatology 61:1239–1250. https://doi.org/10.1002/hep.27647
Patel J, Bettencourt R, Cui J, et al (2016) Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis. Therap Adv Gastroenterol 9:692–701. https://doi.org/10.1177/1756283X16656735
Luo H, Wiens C, Shimakawa A, et al A novel fat and iron quanti cation technique with non-rigid motion-corrected averaging based on non-local means. 3
Pooler BD, Hernando D, Reeder SB (2019) Clinical Implementation of a Focused MRI Protocol for Hepatic Fat and Iron Quantification. American Journal of Roentgenology 213:90–95. https://doi.org/10.2214/AJR.18.20947
Acknowledgements
The authors wish to acknowledge support from the NIH (R01 DK088925, R01 DK100651). The authors also wish to acknowledge support from GE Healthcare and Bracco Diagnostics who provide research support to the University of Wisconsin. Dr. Reeder is a Romnes Faculty Fellow, and has received an award provided by the University of Wisconsin-Madison Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Literature search and material collection were performed by JS and SBR. The first draft of the manuscript was written by JS and critically revised by SBR. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
No authors have any relevant conflicts. Unrelated to this work, Dr. Reeder consults with HeartVista and has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, and Elucent Medical.
Ethical approval
This review article is not under consideration elsewhere. The study or parts of the study were not previously presented or published. Publication of this article has been approved by all authors as well as by the responsible authorities at the institution where the work has been carried out.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Starekova, J., Reeder, S.B. Liver fat quantification: where do we stand?. Abdom Radiol 45, 3386–3399 (2020). https://doi.org/10.1007/s00261-020-02783-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00261-020-02783-1