Quantitative chemical shift-encoded MRI is an accurate method to quantify hepatic steatosis
Corresponding Author
Jens-Peter Kühn MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Address reprint requests to: J.-P.K., Department of Radiology and Neuroradiology, Ernst Moritz Arndt University Greifswald, Ferdinand-Sauerbruch-Straβe NK, Greifswald, D-17475; Germany. E-mail: [email protected]Search for more papers by this authorDiego Hernando PhD
Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
Search for more papers by this authorBirger Mensel MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorPaul C. Krüger MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorTill Ittermann PhD
Institute for Community Medicine, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorJulia Mayerle MD, PhD
Department of Medicine, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorNorbert Hosten MD, PhD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorScott B. Reeder MD, PhD
Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
Departments of Medical Physics, Biomedical Engineering and Medicine, University of Wisconsin, Madison, Wisconsin, USA
Search for more papers by this authorCorresponding Author
Jens-Peter Kühn MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Address reprint requests to: J.-P.K., Department of Radiology and Neuroradiology, Ernst Moritz Arndt University Greifswald, Ferdinand-Sauerbruch-Straβe NK, Greifswald, D-17475; Germany. E-mail: [email protected]Search for more papers by this authorDiego Hernando PhD
Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
Search for more papers by this authorBirger Mensel MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorPaul C. Krüger MD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorTill Ittermann PhD
Institute for Community Medicine, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorJulia Mayerle MD, PhD
Department of Medicine, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorNorbert Hosten MD, PhD
Department of Radiology and Neuroradiology, Ernst Moritz Arndt University, Greifswald, Germany
Search for more papers by this authorScott B. Reeder MD, PhD
Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA
Departments of Medical Physics, Biomedical Engineering and Medicine, University of Wisconsin, Madison, Wisconsin, USA
Search for more papers by this authorThis work is part of the research project Greifswald Approach to Individualized Medicine (GANI_MED). The GANI_MED consortium is funded by the German Federal Ministry of Education and Research (FKZ 03IS2061A) and the Ministry of Cultural Affairs of the Federal State of Mecklenburg – West Pomerania (UG 09 033).
Abstract
Purpose
To compare the accuracy of liver fat quantification using a three-echo chemical shift-encoded magnetic resonance imaging (MRI) technique without and with correction for confounders with spectroscopy (MRS) as the reference standard.
Materials and Methods
Fifty patients (23 women, mean age 56.6 ± 13.2 years) with fatty liver disease were enrolled. Patients underwent T2-corrected single-voxel MRS and a three-echo chemical shift-encoded gradient echo (GRE) sequence at 3.0T. MRI fat fraction (FF) was calculated without and with T2* and T1 correction and multispectral modeling of fat and compared with MRS-FF using linear regression.
Results
The spectroscopic range of liver fat was 0.11%–38.7%. Excellent correlation between MRS-FF and MRI-FF was observed when using T2* correction (R2 = 0.96). With use of T2* correction alone, the slope was significantly different from 1 (1.16 ± 0.03, P < 0.001) and the intercept was different from 0 (1.14% ± 0.50%, P < 0.023). This slope was significantly different than 1.0 when no T1 correction was used (P = 0.001). When T2*, T1, and spectral complexity of fat were addressed, the results showed equivalence between fat quantification using MRI and MRS (slope: 1.02 ± 0.03, P = 0.528; intercept: 0.26% ± 0.46%, P = 0.572).
Conclusion
Complex three-echo chemical shift-encoded MRI is equivalent to MRS for quantifying liver fat, but only with correction for T2* decay and T1 recovery and use of spectral modeling of fat. This is necessary because T2* decay, T1 recovery, and multispectral complexity of fat are processes which may otherwise bias the measurements. J. Magn. Reson. Imaging 2014;39:1494–1501. © 2013 Wiley Periodicals, Inc.
REFERENCES
- 1 Harrison SA, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis 2004; 8: 861–879, ix.
- 2 Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44–52.
- 3 Schwimmer JB. Definitive diagnosis and assessment of risk for nonalcoholic fatty liver disease in children and adolescents. Semin Liver Dis 2007; 27: 312–318.
- 4 Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865–873.
- 5 Stadlmayr A, Aigner E, Steger B, et al. Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia. J Intern Med 2011; 270: 41–49.
- 6 Hui JM, Kench JG, Chitturi S, et al. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 2003; 38: 420–427.
- 7 Schindhelm RK, Diamant M, Heine RJ. Nonalcoholic fatty liver disease and cardiovascular disease risk. Curr Diab Rep 2007; 7: 181–187.
- 8 Kim D, Choi S-Y, Park EH, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology 2012; 56: 605–613.
- 9 Meisamy S, Hines CDG, Hamilton G, 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: 767–775.
- 10 Baumeister SE, Völzke H, Marschall P, et al. Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology 2008; 134: 85–94.
- 11 Ratziu V, Bugianesi E, Dixon J, et al. Histological progression of non-alcoholic fatty liver disease: a critical reassessment based on liver sampling variability. Aliment Pharmacol Ther 2007; 26: 821–830.
- 12 Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898–1906.
- 13 Perrault J, McGill DB, Ott BJ, Taylor WF. Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology 1978; 74: 103–106.
- 14 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: E462–E468.
- 15 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: 568–576.
- 16 Hines CDG, Yu H, Shimakawa A, et al. Quantification of hepatic steatosis with 3-T MR imaging: validation in ob/ob mice. Radiology 2010; 254: 119–128.
- 17 Liu C-Y, 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.
- 18 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: 1122–1134.
- 19 Yu H, McKenzie CA, Shimakawa A, et al. Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. J Magn Reson Imaging 2007; 26: 1153–1161.
- 20 Bydder M, Yokoo T, Hamilton G, et al. Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging 2008; 26: 347–359.
- 21 Reeder SB, Sirlin CB. Quantification of liver fat with magnetic resonance imaging. Magn Reson Imaging Clin N Am 2010; 18: 337–357, ix.
- 22 Reeder SB, Hu HH, Sirlin CB. Proton density fat-fraction: a standardized mr-based biomarker of tissue fat concentration. J Magn Reson Imaging 2012; 36: 1011–1014.
- 23 Yokoo T, Shiehmorteza M, Hamilton G, et al. Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. Radiology 2011; 258: 749–759.
- 24 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 T1. Radiology 2009; 251: 67–76.
- 25 Chang JS, Taouli B, Salibi N, Hecht EM, Chin DG, Lee VS. Opposed-phase MRI for fat quantification in fat-water phantoms with 1H MR spectroscopy to resolve ambiguity of fat or water dominance. AJR Am J Roentgenol 2006; 187: W103–W106.
- 26 de Bazelaire CMJ, Duhamel GD, Rofsky NM, Alsop DC. MR imaging relaxation times of abdominal and pelvic tissues measured in vivo at 3.0 T: preliminary results. Radiology 2004; 230: 652–659.
- 27 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307–310.
- 28 Hernaez R, Lazo M, Bonekamp S, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011; 54: 1082–1090.
- 29 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: W320–W323.
- 30 Xia M-F, Yan H-M, He W-Y, et al. Standardized ultrasound hepatic/renal ratio and hepatic attenuation rate to quantify liver fat content: an improvement method. Obesity (Silver Spring) 2012; 20: 444–452.
- 31 Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, McCullough AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol 2009; 51: 1061–1067.
- 32 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: 281–285.
- 33 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: 729–749.
- 34 Mazhar SM, Shiehmorteza M, Sirlin CB. Noninvasive assessment of hepatic steatosis. Clin Gastroenterol Hepatol 2009; 7: 135–140.
- 35 Merkle EM, Nelson RC. Dual gradient-echo in-phase and opposed-phase hepatic MR imaging: a useful tool for evaluating more than fatty infiltration or fatty sparing. Radiographics 2006; 26: 1409–1418.
- 36 Hussain HK, Chenevert TL, Londy FJ, et al. Hepatic fat fraction: MR imaging for quantitative measurement and display—early experience. Radiology 2005; 237: 1048–1055.
- 37 Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 2001; 22: 2171–2179.
- 38 Wood JC. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005; 106: 1460–1465.
- 39 Hankins JS, McCarville MB, Loeffler RB, et al. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 2009; 113: 4853–4855.
- 40 Bonkovsky HL, Jawaid Q, Tortorelli K, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 421–429.
- 41 George DK, Goldwurm S, MacDonald GA, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114: 311–318.
- 42 Westphalen ACA, Qayyum A, Yeh BM, et al. Liver fat: effect of hepatic iron deposition on evaluation with opposed-phase MR imaging. Radiology 2007; 242: 450–455.
- 43 Schwenzer NF, Machann J, Haap MM, et al. T2* relaxometry in liver, pancreas, and spleen in a healthy cohort of one hundred twenty-nine subjects-correlation with age, gender, and serum ferritin. Invest Radiol 2008; 43: 854–860.
- 44 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: 1332–1339.
- 45 Szczepaniak LS, Babcock EE, Schick F, et al. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol 1999; 276(5 Pt 1): E977–989.
- 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: 487–495.
- 47 Hamilton G, Yokoo T, Bydder M, et al. In vivo characterization of the liver fat 1H MR spectrum. NMR Biomed 2011; 24: 784–790.
- 48 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: 928–934.
- 49 Kuehn J-P, Evert M, Friedrich N, et al. Noninvasive quantification of hepatic fat content using three-echo Dixon magnetic resonance imaging with correction for T2* relaxation effects. Invest Radiol 2011; 46: 783–789.
