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/m
2)
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 mm
3
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
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