Multifrequency MR elastography for assessing hepatic fibrosis in pediatric non-alcoholic fatty liver disease
Jing Guo1, Christian Hudert2, Heiko Tzschätzsch1, Andreas Fehlner1, Florian Dittmann1, Jürgen Braun3, and Ingolf Sack1

1Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 2Charité - Universitätsmedizin Berlin, Berlin, Germany, 3Department of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany

Synopsis

Multifrequency MR elastography (MMRE) was applied to 32 obese pediatric patients with non-alcoholic fatty liver disease (NAFLD). Magnitude shear modulus |G*| which relates to liver stiffness is sensitive to differentiate mild fibrosis (F0-2) from severe fibrosis (F3) with an AUROC of 0.93. The liver stiffness was positively correlated with serum alanine aminotransferase (ALT) and can potentially serve as a quantitative imaging marker for the noninvasive assessment of liver fibrosis in patients with NAFLD.

Target audience

Physicians interested in non-alcoholic fatty liver disease (NAFLD) in pediatric patients.

Purpose

The aim of the study is to use multifrequency MR elastography (MMRE) to detect changes in liver stiffness associated with NAFLD and to discriminate benign fatty liver from mild and advanced fibrosis in children.

Methods

32 patients (age range 10-17 years, 9 females) who are overweight or obese (average BMI: 35.2 kg/m2) and exhibit prolonged elevation of serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (>50 U/l for at least 3 months) were recruited. MMRE (1) was conducted in a 1.5 T scanner (Siemens, Magnetom Sonata) using 7 harmonic frequencies (30 to 60 Hz, 5 Hz increment) as detailed in (2). The full 3D wave field was recorded using a single-shot EPI sequence with motion-encoding gradients. Total acquisition time for 9 consecutive slices of 2.7 × 2.7 × 5 mm3 resolution, 7 frequencies, and 8 wave dynamics was 5 minutes and 8 seconds. MRE wave data was reconstructed using multifrequency dual elasto visco (MDEV) inversion as detailed in (3), yielding parameter maps of the magnitude of the complex shear modulus |G*|. Hepatic fat fraction (HFF) was estimated by the Dixon method. Liver biopsy was performed in all subjects for fibrosis grading according to the METAVIR score and serum biomarkers such as ALT and AST were obtained. Transient elastography (TE) was also applied to all the patients to assess liver stiffness.

Results

Based on histological staging, 23 subjects had no or early fibrosis (4 with F0, 14 with F1 and 5 with F2). 9 subjects had advanced fibrosis with F3. Fig.1 shows MRE magnitude image, shear wave image at 50 Hz drive frequency, HFF map and elastogram (|G*| map) in the central slice of one patient with F2 fibrosis. The patients were divided into two groups (F0-2 and F3) based on biopsy proven fibrosis stage, group-mean values of |G*| and HFF are shown in Fig.2 based on pooling groups into mild (F0-F2) and severe fibrosis (F3). Mann–Whitney U test revealed higher |G*|-values in F3 (3.2±0.5 kPa) than in F0-2 (2.4±0.4 kPa, P <0.001). Values for sensitivity (100%) and specificity (91%) were obtained by a cutoff of 2.71 kPa for detecting severe fibrosis with an AUROC of 0.93 (95% CI 0.84-1.03; p < 0.001). HFF is lower in F0-2 (22±13 %) compared to that of F3 (31±8 %, P <0.05). Additionally, a positive correlation between the liver stiffness and ALT (Person r = 0.64, P = 0.0002, Fig 2c) was obtained. For separating these two patient groups, TE has an unsatisfactory diagnostic accuracy with an AUROC of 0.55.

Discussion

MRE has its advantages over TE when examining obese patients as abdominal wall fat deposition could be a limiting factor for TE (4). For this reason, we achieved a higher diagnostic precession by MRE as compared to TE. Our results are consistent with previous reports of MRE in children with chronic liver disease (5) and adults with NAFLD (6, 7). An increase of HFF was also observed in the F3 group, however, compared to hepatic stiffness measured by MRE, it is less sensitive in differentiating F0-2 and F3. Additionally, we found that liver stiffness is positively correlated with ALT which is related to liver injury. No correlation was found between liver stiffness with AST-to-ALT ratio which is commonly used to identify adult patients with advanced fibrosis. However, recent data suggested that the adult scores may not be accurate for predicting advanced fibrosis in children (4). Our study is limited by small sample size in particular for F2 precluding the separation of F1 and F2. This will be addressed by more patients who are enrolled in a current study.

Conclusion

The MMRE-measured shear modulus |G*| of the liver is sensitive to differentiate F0-2 and F3 in pediatric patients with NAFLD without limitations due to obesity. Liver stiffness was positively correlated with ALT and can potentially serve as a quantitative imaging marker for the noninvasive assessment of liver fibrosis in patients with NAFLD.

Acknowledgements

No acknowledgement found.

References

1. Hirsch S, Guo J, Reiter R, et al. MR elastography of the liver and the spleen using a piezoelectric driver, single-shot wave-field acquisition, and multifrequency dual parameter reconstruction. Magn Reson Med. 2014;71(1):267-77. 2. Guo J, Buning C, Schott E, et al. In vivo abdominal magnetic resonance elastography for the assessment of portal hypertension before and after transjugular intrahepatic portosystemic shunt implantation. Invest Radiol. 2015;50(5):347-51. 3. Jiang X, Asbach P, Streitberger KJ, et al. In vivo high-resolution magnetic resonance elastography of the uterine corpus and cervix. Eur Radiol. 2014;24(12):3025-33. 4. Mansoor S, Collyer E, Alkhouri N. A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease. Curr Gastroenterol Rep. 2015;17(6):23. 5. Xanthakos SA, Podberesky DJ, Serai SD, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014;164(1):186-8. 6.Loomba R, Wolfson T, Ang B, et al. Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study. Hepatology. 2014;60(6):1920-8. 7. Singh S, Venkatesh SK, Loomba R, et al. Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis. Eur Radiol. 2015.

Figures

Fig.1: Magnitude of the MRE signal (a), wave image at 50 Hz vibration frequency (b), HFF map (c) and reconstructed elastogram (|G*| map) (d) in a central slice of one patient.

Fig.2: Mean values of |G*| (a) and HFF (b) in patients from F0-2 and F3 groups. (c) Correlation between the liver stiffness (|G*|) and the ALT in all patients.



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