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

  • Magnetic Resonance
  • Published:
European Radiology Aims and scope Submit manuscript

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.

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Abbreviations

ALT:

Alanine aminotransferase

AUC:

Area under the curve

BMI:

Body mass index

CT:

Computed tomography

HDL:

High-density lipoprotein

HOMA-IR:

Homeostasis model of assessment-insulin resistance

HS:

Hepatic steatosis

ICC:

Intra-class correlation

LDL:

Low density lipoprotein

IR:

Insulin resistance

Met-IFG:

Metabolic syndrome-impaired fasting glucose criteria

Met-IR:

Metabolic syndrome-insulin resistance criteria

MRI:

Magnetic resonance imaging

MRS:

Magnetic resonance spectroscopy

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Steatohepatitis

PDFF:

Proton density fat-fraction

ROC:

Receiver operator characteristics

TE:

Echo time

TR:

Echo repetition

US:

Ultrasound

WC:

Waist circumference

WI:

Wisconsin

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Acknowledgments

The scientific guarantor of this publication is Scott Reeder, MD, PhD. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The authors wish to acknowledge the support of the National Institutes of Health (K24DK102595, R01DK083380, R01DK088925, R01DK100651, K12HD055894, T32DK07758604, UL1TR00427), the Genentech Center for Clinical Research, and the Endocrine Fellows Foundation, as well GE Healthcare, who provides research support to the University of Wisconsin. Jen Eickhoff, PhD kindly provided statistical advice for this manuscript. Dr. Eickhoff has significant statistical expertise and is one of the authors of this paper. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in the Journal of Paediatrics. It should be noted that data acquired from the complete group of subjects was previously reported in a manuscript that proposed a risk assessment model for early detection of HS using common anthropometric and metabolic markers. The only overlapping data are patient characteristics. Methodology: case-control study, performed at one institution.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Jennifer L. Rehm & David B. Allen

  2. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Peter M. Wolfgram

  3. Department of Radiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Diego Hernando & Scott B. Reeder

  4. Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Jens C. Eickhoff

  5. Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Scott B. Reeder

  6. Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Scott B. Reeder

  7. Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Scott B. Reeder

  8. Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI, 53715-4108, USA

    Scott B. Reeder

Authors
  1. Jennifer L. Rehm
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  2. Peter M. Wolfgram
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  3. Diego Hernando
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  4. Jens C. Eickhoff
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Correspondence to Jennifer L. Rehm.

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Rehm, J.L., Wolfgram, P.M., Hernando, D. et al. Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women. Eur Radiol 25, 2921–2930 (2015). https://doi.org/10.1007/s00330-015-3724-1

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  • DOI: https://doi.org/10.1007/s00330-015-3724-1

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