Jia Xu1, Xuan Wang1, Yan You2, Qin Wang1, Hui Liu3, Jing Lei1, Huadan Xue1, and Zhengyu Jin1
1Department of Radiology, Peking Union Medical College Hospital, Beijing, China, People's Republic of, 2Department of Pathology, Peking Union Medical College Hospital, Beijing, China, People's Republic of, 3Siemens Ltd. China, Shanghai, China, People's Republic of
Synopsis
To evaluate
regional liver function preoperatively is of great value in planning
surgical management. Our Aim is to investigate the potential of Gd-EOB-DTPA
enhanced MRI in evaluating hepatic function in rats with liver fibrosis. Parameters
calculated from Gd-EOB-DTPA enhanced MRI exhibited moderate to high correlation
with plasma indocyanine green retention rate at 15 minutes after intravenous
injection of ICG (ICG R15) in rats with liver fibrosis, indicating its
potential in liver function evaluation. Introduction and Purpose
Preoperative
evaluation of liver function is crucial in patients candidate to surgical
management, especially in those with liver fibrosis
1. Current
approaches for assessing liver function mainly
include Child-Pugh classification, MELD score, indocyanine green (ICG) plasma
clearance test, 3-dimensional CT volumetry, and 99mTc-GSA SPECT. However, most of
them are unable to evaluate regional liver function, and the spatial resolution
of 99mTc-GSA SPECT is limited, so none of these methods can fully meet the
clinical requirements
2,3. Gd-EOB-DTPA is a hepatocyte-specific magnetic
resonance imaging (MRI) contrast agent, the uptake and metabolism of which is related
to hepatocyte function
4. The aim of this study was to investigate
the potential of Gd-EOB-DTPA enhanced MRI [including dynamic contrast-enhanced (DCE)
images, as well as multiple hepatocyte-phase and T1 mapping images] in evaluating
hepatic function in rats with liver fibrosis, and to discover specific imaging
biomarkers for hepatic function.
Methods
Forty
male Sprague-Dawley rats were used in this study. Liver fibrosis in rats was
induced by carbon tetrachloride intraperitoneal injection for 4-12 weeks
(n=30). In control group (n=10) normal saline was applied. At 4, 8 and 12 weeks, rats from both control group and
experiment group were randomly selected to undergo magnetic resonance (MR)
exams. MR exams were performed using a 3.0T scanner (Siemens MAGNETOM Skyra) with
a wrist coil. The MR protocol contained DCE sequence, multiple hepatocyte-phase
acquisitions and T1 mapping series. TWIST-VIBE sequence was used for DCE
imaging, in which sixty measurements including 3 pre-contrast ones were taken
at a time interval of 3 s up to 3 min after the injection of the contrast agent.
For multi-hepatocyte-phase images, single phase TWIST-VIBE sequence was used.
Twelve datasets were acquired at 5, 10, 15, 20, 25, 30, 35, 45, 50, 55 and
60min after the injection of Gd-EOB-DTPA. Double Flip Angel T1 3D VIBE sequence
was used for T1 mapping imaging. Seven series were acquired before and at 10,
20, 30, 40, 50 and 60min after the injection. Data were analyzed using a
commercial available post-processing workstation (Siemens MMWP, tissue 4D). The
following parameters were obtained: 1) liver perfusion parameters such as maximum
relative enhancement (RE
max) and the time of maximum RE (T
max); 2) hepatocyte-phase parameters such as relative
enhancement (RE) at different time point and elimination half-life of RE (T
RE1/2); 3) T1
mapping parameters such as T1 reduction rate at different time point (△T1%) and elimination half-life of △T1% (T
△T1%1/2). The ICG clearance test was performed using
0.5 mg/kg ICG after MR exams. Plasma ICG retention rate at 15 minutes after
intravenous injection of ICG (ICG R15) was calculated. METAVIR score
was used for pathological grading of liver fibrosis: normal (F0), mild fibrosis
(F1-2), and advanced fibrosis (F3-4). SPSS 21.0 was used for statistical
analysis. Pearson correlation coefficient assessment was used to evaluate the
relationship between the ICG R15 values and the MR parameters.
Results
Twenty-two rats completed ICG clearance test in the end
of the study, including normal (n=8), mild fibrosis (n=9) and advanced fibrosis
(n=5). Nineteen of these 22 rats completed DCE-MR and multiple hepatocyte-phase acquisitions,
while 10 completed T1 mapping acquisitions. ICG R15 was significantly higher in
advanced fibrosis than normal and mild fibrosis (
P=0.011,
P=0.006). T
max
and T
RE1/2 increased as the ICG R15 increased, the correlation coefficient with
ICG R15 were 0.531 (
P=0.019) and
0.535 (
P=0.018) respectively. T
△T1%1/2, △T1%
30min, △T1%
40min, △T1%
50min increased
as the ICG R15 value increased, the correlation coefficient were 0.697 (
P=0.02) , 0.811 (
P=0.033), 0.673 (
P=0.043),
0.757 (
P=0.028) respectively (Fig 1, Fig
2). RE
max and RE at different time points did not show significant correlation
with ICG R15.
Discussion
Liver function decreased as liver fibrosis progressed. The time of
maximum RE, half elimination time of RE and half elimination time of T1
reduction rate increased as liver function decreased, indicating a slower uptake
of Gd-EOB-DTPA and a longer excretion time in rats with impaired liver function.
Besides, at hepatocyte-phase, rats with liver dysfunction tend to retent more
contrast agent in liver parenchyma, resulting in a higher T1 reduction rate at
30、40、50min.
Conclusion
Parameters
calculated from Gd-EOB-DTPA enhanced MRI such as T
max , T
RE1/2, T
△T1%1/2, △T1%
30min, △T1%
40min, and △T1%
50min exhibited moderate to high correlation
with ICG R15 in rats with liver fibrosis. Gd-EOB-DTPA enhanced MRI could be
helpful for the evaluation of liver function.
Acknowledgements
No acknowledgement found.References
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