Verena Carola Obmann1, Nando Mertineit1, Annalisa Berzigotti2, Christina Marx1, Lukas Ebner1, Michael Ith1, Johannes Heverhagen1, Andreas Christe1, and Adrian Huber1
1Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern, Switzerland, 2Visceral Surgery and Medicine, Inselspital, Bern, Switzerland
Synopsis
We hypothesized, that susceptibility weighted imaging
(SWI) and T2*-mapping are dependent on liver steatosis, which should be taken
into account when using these parameters to grade liver fibrosis and cirrhosis.
In this study 184 patients underwent multiparametric MRI at 3T including SWI,
T1/T2* mapping as well as proton density fat fraction quantification and MR
elastography as reference standard. SWI and T2* were both highly dependent on
the degree of liver steatosis (p<0.001). However, SWI allowed a better
differentiation between liver fibrosis grades (p <0.001) than T2*.
Nevertheless, both parameters are useful predictors for liver fibrosis when
using a multiparametric approach.
Introduction
MR T2*-mapping is widely used to non-invasively
quantify liver iron content and increased liver iron content represents an
important background alteration in liver fibrosis (1), since cirrhotic nodules contain hemosiderotic
depositions (2) and increasing fibrosis stages correlate with serum
ferritin and liver iron content. Similarly, SWI is routinely used to detect
hemosiderotic products in the brain and recent technical advances allow for
abdominal applications as well. Balassy et al. showed that increased SWI liver
to muscle ratio (LMR) correlates with increasing liver fibrosis grade (3). The purpose of this study was to show that both
susceptibility weighted imaging (SWI) and T2*-mapping are dependent on liver
steatosis, which should be taken into account when using these parameters to
grade liver fibrosis and cirrhosis.
Methods
In this
prospective cross-sectional HIPAA conform, IRB approved study a total of 184
patients without focal liver disease underwent multiparametric MRI at 3T
including susceptibility weighted imaging (SWI), T1/T2* mapping, proton density
fat fraction (PDFF) quantification and MR elastography. For T2* mapping, a
multiecho gradient echo (GRE) single breath-hold sequence (12 echoes with a TE
between 0.93-14.2 ms, TR of 200 ms, FA 18°, FOV 400, 10-mm slice thickness) was
performed. For SWI we used a 3D GRE based sequence (TE of 20 ms, TR of 27 ms,
in plane resolution of 2.1 x 1.4 mm, through plane 4 mm with 10% slice
oversampling, FOV 350, FA 15°). T1 mapping was acquired with an axial MOLLI
single breath-hold sequence (echo time (TE) of 1.01 ms, TR of 740 ms, TI 225
ms, FA 35°, 8-mm slice thickness, FOV 384, matrix 154 x 192 pixels).
SWI, T2* and T1
values measured in the liver (4 locations), as well as their
liver-to-muscle-ratio (LMR, measured in the paraspinal muscles) were compared
between patients with different steatosis grades (PDFF <5%, 5-10%, 10-20%
and >20%) in patients with normal stiffness and between patients with
normal, slightly and moderately increased liver stiffness (<2.8 kPa, 2.8-3.5
kPa and >3.5 kPa, respectively). ANOVA with Bonferroni-corrected post-hoc
tests as well as multivariate analysis were used to compare between groups and
parameters.Results
Signal intensity on SWI was 98 ± 30 and T2* relaxation
time 22 ± 4 ms in patients with PDFF <5% and it was 42 ± 16 and 15 ± 2 in
patients with PDFF>20%, respectively. SWI and T2* were thus both highly
dependent on the degree of liver steatosis (p<0.001). However, SWI allowed a
better differentiation between liver fibrosis grades (p<0.001) than T2*
(p=0.05). The liver-to-muscle ratios (LMR) were not superior to the respective
parameters alone, for T2* even worse. SWI and T2* in the liver were independent
predictors for liver fibrosis if evaluated in combination with PDFF, T1 and
age. A combination of SWI or T2* with age, PDFF and T1 in a multiparametric
model showed a multiple r2 of 0.38 and 0.44, respectively.Discussion
This study demonstrates that both SWI and T2*
relaxation times are dependent on the presence of liver fat, but SWI is less
effected than T2*. While there is sparse literature about the effect of fat on
SWI, fat is a known influencer of T2* relaxation time (4). The better performance of SWI to separate degrees of
fibrosis than T2* might be explained by the fact that SWI uses both phase and
magnitude information. In contrast, T2* mapping is solely based on the
magnitude information, but has the advantage of absolute quantification of
T2*-relaxation times. These technical differences are the reason why SWI is
more susceptibility weighted than T2*. Thus, SWI might allow liver fibrosis
characterization better than T2* mapping as it is able to detect siderotic
nodules at a much earlier stage (5, 6). While the advantage of T2* in the quantification of
liver iron is extensively published in the literature, there are only a few
studies describing its value in the assessment of liver fibrosis, mostly in a
preclinical setting (7).Conclusion
SWI and T2*-mapping are highly dependent on liver
steatosis grades, but SWI is less effected than T2*. Nevertheless, both
parameters are useful predictors for liver fibrosis when using a
multiparametric approach. While SWI performed better than T2* to separate
patients with and without liver fibrosis, T2* performed slightly better in a
multiparametric combination with MR elastography, PDFF, and T1.Acknowledgements
This work was supported by the Swiss National Science Foundation
Research Equipment (R'Equip Grant) and Matching Fund from the University of
Bern as well as the foundation to fight against cancer.References
1. Kowdley KV. Iron Overload in Patients
With Chronic Liver Disease. Gastroenterology & Hepatology.
2016;12(11):695-8.
2. Kayali Z, Ranguelov
R, Mitros F, Shufelt C, Elmi F, Rayhill SC, et al. Hemosiderosis is associated
with accelerated decompensation and decreased survival in patients with
cirrhosis. Liver international : official journal of the International
Association for the Study of the Liver. 2005;25(1):41-8.
3. Balassy C, Feier D,
Peck-Radosavljevic M, Wrba F, Witoszynskyj S, Kiefer B, et al.
Susceptibility-weighted MR imaging in the grading of liver fibrosis: a
feasibility study. Radiology. 2014;270(1):149-58.
4. Hernando D, Cook RJ,
Diamond C, Reeder SB. Magnetic susceptibility as a B0 field strength
independent MRI biomarker of liver iron overload. Magnetic resonance in
medicine. 2013;70(3):648-56.
5. Dai Y, Zeng M, Li R,
Rao S, Chen C, DelProposto Z, et al. Improving detection of siderotic nodules
in cirrhotic liver with a multi-breath-hold susceptibility-weighted imaging
technique. Journal of magnetic resonance imaging : JMRI. 2011;34(2):318-25.
6. Chen W, DelProposto
Z, Wu D, Wang J, Jiang Q, Xuan S, et al. Improved siderotic nodule detection in
cirrhosis with susceptibility-weighted magnetic resonance imaging: a
prospective study. PloS one. 2012;7(5):e36454.
7. Muller A, Hochrath K, Stroeder J, Hittatiya K, Schneider G,
Lammert F, et al. Effects of Liver Fibrosis Progression on Tissue Relaxation
Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance
Imaging. Biomed Res Int. 2017;2017:8720367.