Skip to main content
Top
Published in: European Radiology 10/2015

01-10-2015 | Magnetic Resonance

Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women

Authors: Jennifer L. Rehm, Peter M. Wolfgram, Diego Hernando, Jens C. Eickhoff, David B. Allen, Scott B. Reeder

Published in: European Radiology | Issue 10/2015

Login to get access

Abstract

Objectives

To compare complex quantitative magnetic resonance imaging (MRI) with MR spectroscopy (MRS) for quantification of hepatic steatosis (HS) and determine clinically significant MRI-based thresholds of HS in female youths.

Methods

This prospective, cross-sectional study was conducted in 132 healthy females (11–22 years, mean 13.3 ± 2). Proton density fat-fraction (PDFF) was measured using complex quantitative MRI and MRS. Body mass index (BMI), fasting labs [glucose, insulin, alanine aminotransferase (ALT), and other metabolic markers] were obtained. Outcomes were measured using regression analysis, Spearman-rank correlation, and receiver operator characteristics (ROC) analysis. HS was defined as MRI-PDFF >5.6 %.

Results

HS was detected by MRI-PDFF in 15 % of all subjects. Linear regression demonstrated excellent correlation and agreement [r2 = 0.96, slope = 0.97 (95 %CI: 0.94–1.00), intercept = 0.78 % (95 %CI: 0.58–0.98 %)] between MRI-PDFF and MRS-PDFF. MRI-PDFF had a sensitivity of 100 % (95 %CI: 0.79–1.00), specificity of 96.6 % (95 %CI: 0.91–0.99), and a kappa index of 87 % (95 %CI: 0.75–0.99) for identifying HS. In overweight subjects with HS, MRI-PDFF correlated with ALT (r = 0.84, p < 0.0001) and insulin (r = 0.833, p < 0.001), but not with BMI or WC. ROC analysis ascertained an optimal MRI-PDFF threshold of 3.5 % for predicting metabolic syndrome (sensitivity = 76 %, specificity = 83 %).

Conclusion

Complex quantitative MRI demonstrates strong correlation and agreement with MRS to quantify hepatic triglyceride content in adolescent girls and young women. A low PDFF threshold is predictive of metabolic syndrome in this population.

Key points

Confounder-corrected quantitative MRI (ccqMRI) effectively measures hepatic triglyceride content in adolescent girls.
MRS and ccqMRI strongly correlate in liver proton density fat-fraction (PDFF) detection.
A PDFF threshold of 3.5 % may be predictive of paediatric metabolic syndrome.
Literature
1.
go back to reference Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P (2009) The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 58:1538–1544PubMedCentralCrossRefPubMed Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P (2009) The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 58:1538–1544PubMedCentralCrossRefPubMed
2.
go back to reference Clark JM (2006) The Epidemiology of Nonalcoholic Fatty Liver Disease in Adults. J Clin Gastroenterol Nonalcoholic Steatohepatitis 40 Supplement:S5-S10 Clark JM (2006) The Epidemiology of Nonalcoholic Fatty Liver Disease in Adults. J Clin Gastroenterol Nonalcoholic Steatohepatitis 40 Supplement:S5-S10
4.
go back to reference Denzer C, Thiere D, Muche R et al (2009) Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab 94:3872–3881CrossRefPubMed Denzer C, Thiere D, Muche R et al (2009) Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab 94:3872–3881CrossRefPubMed
5.
go back to reference Ko JS, Yoon JM, Yang HR et al (2009) Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci 54:2225–2230CrossRefPubMed Ko JS, Yoon JM, Yang HR et al (2009) Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci 54:2225–2230CrossRefPubMed
6.
go back to reference Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350CrossRefPubMed Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350CrossRefPubMed
7.
go back to reference Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE (2003) Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 143:500–505CrossRefPubMed Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE (2003) Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 143:500–505CrossRefPubMed
8.
go back to reference Utzschneider KM, Kahn SE (2006) Review: the role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 91:4753–4761CrossRefPubMed Utzschneider KM, Kahn SE (2006) Review: the role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 91:4753–4761CrossRefPubMed
9.
go back to reference Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112CrossRefPubMed Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112CrossRefPubMed
10.
go back to reference Ong JP, Younossi ZM (2007) Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 11:1–16, viiCrossRefPubMed Ong JP, Younossi ZM (2007) Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 11:1–16, viiCrossRefPubMed
11.
go back to reference Schwimmer JB, Behling C, Newbury R et al (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42:641–649CrossRefPubMed Schwimmer JB, Behling C, Newbury R et al (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42:641–649CrossRefPubMed
12.
go back to reference Manco M, Alisi A, Nobili V (2008) Risk of severe liver disease in NAFLD with normal ALT levels: a pediatric report. Hepatology 48:2087–2088, author reply 2088CrossRefPubMed Manco M, Alisi A, Nobili V (2008) Risk of severe liver disease in NAFLD with normal ALT levels: a pediatric report. Hepatology 48:2087–2088, author reply 2088CrossRefPubMed
13.
go back to reference Fraser A, Longnecker MP, Lawlor DA (2007) Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. Gastroenterology 133:1814–1820PubMedCentralCrossRefPubMed Fraser A, Longnecker MP, Lawlor DA (2007) Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. Gastroenterology 133:1814–1820PubMedCentralCrossRefPubMed
14.
go back to reference Mofrad P, Contos MJ, Haque M et al (2003) Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37:1286–1292CrossRefPubMed Mofrad P, Contos MJ, Haque M et al (2003) Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37:1286–1292CrossRefPubMed
15.
go back to reference Schwimmer JB (2007) Definitive diagnosis and assessment of risk for nonalcoholic fatty liver disease in children and adolescents. Semin Liver Dis 27:312–318CrossRefPubMed Schwimmer JB (2007) Definitive diagnosis and assessment of risk for nonalcoholic fatty liver disease in children and adolescents. Semin Liver Dis 27:312–318CrossRefPubMed
16.
go back to reference Fabbrini E, Conte C, Magkos F (2009) Methods for assessing intrahepatic fat content and steatosis. Curr Opin Clin Nutr Metab Care 12:474–481CrossRefPubMed Fabbrini E, Conte C, Magkos F (2009) Methods for assessing intrahepatic fat content and steatosis. Curr Opin Clin Nutr Metab Care 12:474–481CrossRefPubMed
17.
go back to reference Thomsen C, Becker U, Winkler K, Christoffersen P, Jensen M, Henriksen O (1994) Quantification of liver fat using magnetic resonance spectroscopy. Magn Reson Imaging 12:487–495CrossRefPubMed Thomsen C, Becker U, Winkler K, Christoffersen P, Jensen M, Henriksen O (1994) Quantification of liver fat using magnetic resonance spectroscopy. Magn Reson Imaging 12:487–495CrossRefPubMed
18.
go back to reference Wong WF, Northrup SR, Herrick RC, Glombicki AP, Wood RP, Morrisett JD (1994) Quantitation of lipid in biological tissue by chemical shift magnetic resonance imaging. Magn Reson Med 32:440–446CrossRefPubMed Wong WF, Northrup SR, Herrick RC, Glombicki AP, Wood RP, Morrisett JD (1994) Quantitation of lipid in biological tissue by chemical shift magnetic resonance imaging. Magn Reson Med 32:440–446CrossRefPubMed
19.
go back to reference Yokoo T, Bydder M, Hamilton G et al (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 251:67–76PubMedCentralCrossRefPubMed Yokoo T, Bydder M, Hamilton G et al (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 251:67–76PubMedCentralCrossRefPubMed
20.
go back to reference Yokoo T, Shiehmorteza M, Hamilton G et al (2011) Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. Radiology 258:749–759PubMedCentralCrossRefPubMed Yokoo T, Shiehmorteza M, Hamilton G et al (2011) Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. Radiology 258:749–759PubMedCentralCrossRefPubMed
21.
go back to reference Hines CD, Frydrychowicz A, Hamilton G et al (2011) T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:873–881PubMedCentralCrossRefPubMed Hines CD, Frydrychowicz A, Hamilton G et al (2011) T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:873–881PubMedCentralCrossRefPubMed
22.
go back to reference Meisamy S, Hines CD, 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 258:767–775PubMedCentralCrossRefPubMed Meisamy S, Hines CD, 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 258:767–775PubMedCentralCrossRefPubMed
23.
go back to reference Reeder SB, Hu HH, Sirlin CB (2012) Proton density fat-fraction: a standardized mr-based biomarker of tissue fat concentration. J Magn Reson Imaging. doi:10.1002/jmri.23741 Reeder SB, Hu HH, Sirlin CB (2012) Proton density fat-fraction: a standardized mr-based biomarker of tissue fat concentration. J Magn Reson Imaging. doi:10.​1002/​jmri.​23741
24.
go back to reference Tang A, Tan J, Sun M et al (2013) Nonalcoholic Fatty Liver. MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis. Radiology, Disease. doi:10.1148/radiol.12120896 Tang A, Tan J, Sun M et al (2013) Nonalcoholic Fatty Liver. MR Imaging of Liver Proton Density Fat Fraction to Assess Hepatic Steatosis. Radiology, Disease. doi:10.​1148/​radiol.​12120896
26.
go back to reference Taylor SJ, Whincup PH, Hindmarsh PC, Lampe F, Odoki K, Cook DG (2001) Performance of a new pubertal self-assessment questionnaire: a preliminary study. Paediatr Perinat Epidemiol 15:88–94CrossRefPubMed Taylor SJ, Whincup PH, Hindmarsh PC, Lampe F, Odoki K, Cook DG (2001) Performance of a new pubertal self-assessment questionnaire: a preliminary study. Paediatr Perinat Epidemiol 15:88–94CrossRefPubMed
27.
go back to reference Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMed Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115:e500–e503CrossRefPubMed
28.
go back to reference (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555-576 (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555-576
29.
go back to reference Fernandez JR, Redden DT, Pietrobelli A, Allison DB (2004) Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 145:439–444CrossRefPubMed Fernandez JR, Redden DT, Pietrobelli A, Allison DB (2004) Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 145:439–444CrossRefPubMed
30.
go back to reference Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH (2003) Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 157:821–827CrossRefPubMed Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH (2003) Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 157:821–827CrossRefPubMed
31.
go back to reference Calcaterra V, Klersy C, Muratori T et al (2008) Prevalence of metabolic syndrome (MS) in children and adolescents with varying degrees of obesity. Clin Endocrinol 68:868–872CrossRef Calcaterra V, Klersy C, Muratori T et al (2008) Prevalence of metabolic syndrome (MS) in children and adolescents with varying degrees of obesity. Clin Endocrinol 68:868–872CrossRef
32.
go back to reference Brau AC, Beatty PJ, Skare S, Bammer R (2008) Comparison of reconstruction accuracy and efficiency among autocalibrating data-driven parallel imaging methods. Magn Reson Med 59:382–395PubMedCentralCrossRefPubMed Brau AC, Beatty PJ, Skare S, Bammer R (2008) Comparison of reconstruction accuracy and efficiency among autocalibrating data-driven parallel imaging methods. Magn Reson Med 59:382–395PubMedCentralCrossRefPubMed
33.
go back to reference Yu H, Shimakawa A, McKenzie CA, Brodsky E, Brittain JH, Reeder SB (2008) Multiecho water-fat separation and simultaneous R2* estimation with multifrequency fat spectrum modeling. Magn Reson Med 60:1122–1134PubMedCentralCrossRefPubMed Yu H, Shimakawa A, McKenzie CA, Brodsky E, Brittain JH, Reeder SB (2008) Multiecho water-fat separation and simultaneous R2* estimation with multifrequency fat spectrum modeling. Magn Reson Med 60:1122–1134PubMedCentralCrossRefPubMed
34.
go back to reference Bydder M, Yokoo T, Hamilton G et al (2008) Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging 26:347–359PubMedCentralCrossRefPubMed Bydder M, Yokoo T, Hamilton G et al (2008) Relaxation effects in the quantification of fat using gradient echo imaging. Magn Reson Imaging 26:347–359PubMedCentralCrossRefPubMed
35.
go back to reference Yu H, Shimakawa A, Hines CD et al (2011) Combination of complex-based and magnitude-based multiecho water-fat separation for accurate quantification of fat-fraction. Magn Reson Med 66:199–206PubMedCentralCrossRefPubMed Yu H, Shimakawa A, Hines CD et al (2011) Combination of complex-based and magnitude-based multiecho water-fat separation for accurate quantification of fat-fraction. Magn Reson Med 66:199–206PubMedCentralCrossRefPubMed
36.
go back to reference Liu CY, McKenzie CA, Yu H, Brittain JH, Reeder SB (2007) Fat quantification with IDEAL gradient echo imaging: correction of bias from T(1) and noise. Magn Reson Med 58:354–364CrossRefPubMed Liu CY, McKenzie CA, Yu H, Brittain JH, Reeder SB (2007) Fat quantification with IDEAL gradient echo imaging: correction of bias from T(1) and noise. Magn Reson Med 58:354–364CrossRefPubMed
37.
go back to reference Szczepaniak LS, Nurenberg P, Leonard D et al (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–E468CrossRefPubMed Szczepaniak LS, Nurenberg P, Leonard D et al (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–E468CrossRefPubMed
38.
go back to reference 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 30:145–152PubMedCentralCrossRefPubMed 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 30:145–152PubMedCentralCrossRefPubMed
39.
go back to reference Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310CrossRefPubMed Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310CrossRefPubMed
40.
go back to reference Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174CrossRefPubMed Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174CrossRefPubMed
41.
go back to reference Linder K, Springer F, Machann J et al (2014) Relationships of body composition and liver fat content with insulin resistance in obesity-matched adolescents and adults. Obesity (Silver Spring) 22:1325–1331CrossRef Linder K, Springer F, Machann J et al (2014) Relationships of body composition and liver fat content with insulin resistance in obesity-matched adolescents and adults. Obesity (Silver Spring) 22:1325–1331CrossRef
42.
go back to reference Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S (2008) Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 118:277–283PubMedCentralCrossRefPubMed Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S (2008) Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 118:277–283PubMedCentralCrossRefPubMed
43.
go back to reference Alderete TL, Toledo-Corral CM, Desai P, Weigensberg MJ, Goran MI (2013) Liver fat has a stronger association with risk factors for type 2 diabetes in african-american compared with Hispanic adolescents. J Clin Endocrinol Metab 98:3748–3754PubMedCentralCrossRefPubMed Alderete TL, Toledo-Corral CM, Desai P, Weigensberg MJ, Goran MI (2013) Liver fat has a stronger association with risk factors for type 2 diabetes in african-american compared with Hispanic adolescents. J Clin Endocrinol Metab 98:3748–3754PubMedCentralCrossRefPubMed
44.
go back to reference Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C (2011) Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol 17:3082–3091PubMedCentralCrossRefPubMed Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C (2011) Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol 17:3082–3091PubMedCentralCrossRefPubMed
45.
go back to reference Schwimmer JB, Dunn W, Norman GJ et al (2010) SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 138:1357–1364, 1364.e1351-1352PubMedCentralCrossRefPubMed Schwimmer JB, Dunn W, Norman GJ et al (2010) SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology 138:1357–1364, 1364.e1351-1352PubMedCentralCrossRefPubMed
Metadata
Title
Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women
Authors
Jennifer L. Rehm
Peter M. Wolfgram
Diego Hernando
Jens C. Eickhoff
David B. Allen
Scott B. Reeder
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 10/2015
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-015-3724-1

Other articles of this Issue 10/2015

European Radiology 10/2015 Go to the issue