Liver stiffness in pediatric subjects is lower than in adults, and increases with age: a multifrequency MR elastography study
Emily Etchell1, Lauriane Jugé 1,2, Alice Hatt1, Ralph Sinkus3, and Lynne E. Bilston1,4

1Neuroscience Research Australia, Randwick, NSW, Australia, 2School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia, 3BHF Centre of Excellence, Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 4Prince of Wales Clinical School, University of New South Wales, Kensington, NSW, Australia

Synopsis

Magnetic resonance (MR) elastography provides clinical information for chronic hepatic disorders by quantifying an increase in liver stiffness compared to heathy baseline values. Thus far however, baseline stiffness values have only been reported for adults. We aimed to fill this gap by quantifying healthy liver stiffness of children and adolescents. Results showed that pediatric liver stiffness increases with age during normal development, approaching adult values during adolescence. This implies that comparing pediatric liver stiffness measurements to adult baseline values when using MR elastography may miss disease or underestimate disease severity.

Introduction

Magnetic resonance (MR) elastography is capable of non-invasively measuring mechanical properties of liver and provides clinically useful information for chronic hepatic disorders in adults1-5. Such a technique could also be useful for hepatic disorders that occur in childhood, such as seen in recent studies 6-9. However, none of these studies have reported data for healthy pediatric liver to which pathological liver stiffness can be compared; even though differences between adult and pediatric mechanical properties of other soft tissues have been reported, e.g. in muscle 10 and brain 11. We aimed to measure the mechanical properties of liver in healthy pediatric and adult participants using MR elastography to test the hypothesis that pediatric liver stiffness differs from adults and changes during maturation.

Methods

This study was approved by the local human research ethics committee and adheres to the Declaration of Helsinki. MR elastography at 28, 56 and 84Hz was performed on a 3-T scanner (Philips AchievaTX) to measure liver shear moduli (G*) of 13 heathy children aged from 5 to 14 years (7 males, BMI 18 ± 2 kg/m2), 11 healthy adolescents aged from 15 to 18 years (6 males, BMI 21 ± 2 kg/m2), and 10 healthy adults aged from 22 to 36 years (5 males, BMI 24 ± 2 kg/m2). Mean and standard deviation were calculated for G* at 28, 56 and 84 Hz, and the frequency dependence of G*. All variables were compared between groups using ANOVA test followed by a Tukey’s multiple comparison test.

Results

Liver G* in children and adolescents was significantly lower than in adults at 56 Hz and 84 Hz but not at 28 Hz (ANOVA, P=0.009, P=0.0003, P=0.40 respectively, Fig. 1 from A to C). G* varied less with frequency in children and adolescents than adults (ANOVA, P=0.0009, Fig 1D).

Conclusions

Liver stiffness in children as measured by MR elastography was lower than in adults, with greater differences at higher frequencies, and stiffness increases with age during normal development, approaching adult values during adolescence.

Clinical implications

Given that heathy pediatric liver stiffness is lower than in adults, comparing the liver stiffness of pediatric patients with suspected fibrotic liver disease to adult baseline values may underestimate disease severity, or miss low grade changes, particularly in pre-adolescent children.

Acknowledgements

This study was funded by a discovery projects grant from the Australian Research Council. We also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King’s College Hospital NHS Foundation Trust.

References

1. Yin M, Talwalkar JA, Glaser KJ, Manduca A, Grimm RC, Rossman PJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol H. 2007;5(10):1207-13.

2. Asbach P, Klatt D, Schlosser B, Biermer M, Muche M, Rieger A, et al. Viscoelasticity-based Staging of Hepatic Fibrosis with Multifrequency MR Elastography. Radiology. 2010;257(1):80-6.

3. Huwart L, Peeters F, Sinkus R, Annet L, Salameh N, ter Beek LC, et al. Liver fibrosis: non-invasive assessment with MR elastography. Nmr in Biomedicine. 2006;19(2):173-9.

4. Huwart L, Sempoux C, Vicaut E, Salameh N, Annet L, Danse E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135(1):32-40.

5. Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011;259(3):749-56.

6. Serai SD, Towbin AJ, Podberesky DJ. Pediatric liver MR elastography. Dig Dis Sci. 2012;57(10):2713-9.

7. Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014;164(1):186-8.

8. Binkovitz LA, El-Youssef M, Glaser KJ, Yin M, Binkovitz AK, Ehman RL. Pediatric MR elastography of hepatic fibrosis: principles, technique and early clinical experience. Pediatr Radiol. 2012;42(4):402-9.

9. Serai SD, Wallihan DB, Venkatesh SK, Ehman RL, Campbell KM, Sticka J, et al. Magnetic resonance elastography of the liver in patients status-post fontan procedure: feasibility and preliminary results. Congenit Heart Dis. 2014;9(1):7-14.

10. Alnaqeeb MA, Alzaid NS, Goldspink G. Connective-Tissue Changes and Physical-Properties of Developing and Aging Skeletal-Muscle. J Anat. 1984;139(Dec):677-89.

11. Gefen A, Gefen N, Zhu QL, Raghupathi R, Margulies SS. Age-dependent changes in material properties of the brain and braincase of the rat. J Neurotraum. 2003;20(11):1163-77.

Figures

Box and whisker plots of liver shear modulus (G*, kPa) at (A) 28, (B) 56, and (C) 84 Hz and (D) frequency dependence (kPa/Hz) for children, adolescents and adult participants. Significant Tukey’s comparisons test are indicated by * = P<0.05.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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