nach oben

European Radiology

Erschienen in:

01.10.2015 | Magnetic Resonance

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

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

Erschienen in: European Radiology | Ausgabe 10/2015

Einloggen, um Zugang zu erhalten

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.

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

Clark JM (2006) The Epidemiology of Nonalcoholic Fatty Liver Disease in Adults. J Clin Gastroenterol Nonalcoholic Steatohepatitis 40 Supplement:S5-S10

Loomba R, Sirlin CB, Schwimmer JB, Lavine JE (2009) Advances in pediatric nonalcoholic fatty liver disease. Hepatology 50:1282–1293PubMedCentralCrossRefPubMed

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

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

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

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

Utzschneider KM, Kahn SE (2006) Review: the role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 91:4753–4761CrossRefPubMed

Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43:S99–S112CrossRefPubMed

10.

Ong JP, Younossi ZM (2007) Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 11:1–16, viiCrossRefPubMed

11.

Schwimmer JB, Behling C, Newbury R et al (2005) Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42:641–649CrossRefPubMed

12.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

25.

Rehm JL, Connor EL, Wolfgram PM, Eickhoff JC, Reeder SB, Allen DB (2014) Predicting Hepatic Steatosis in a Racially and Ethnically Diverse Cohort of Adolescent Girls. J Pediatr. doi:10.1016/j.jpeds.2014.04.019 PubMedCentralPubMed

26.

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.

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.

(2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555-576

29.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310CrossRefPubMed

40.

Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159–174CrossRefPubMed

41.

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.

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.

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.

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.

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

Titel: Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women
verfasst von: Jennifer L. Rehm
Peter M. Wolfgram
Diego Hernando
Jens C. Eickhoff
David B. Allen
Scott B. Reeder
Publikationsdatum: 01.10.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: European Radiology / Ausgabe 10/2015
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-015-3724-1

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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