Qihua Yang1, Taihui Yu1, Hui Zhang2, Hua Guo2, Yingjie Mei3, Ziliang Cheng1, Jingwen Huang1, and Biling Liang1
1Radiology Dept, Sun Yat-sen Memorial Hospital, Guangzhou, China, People's Republic of, 2Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, People's Republic of, 3Philips Healthcare, Guangzhou, China, People's Republic of
Synopsis
To find out the relationship among T1rho,
liver fibrosis stages and liver function, MRI including T1rho sequence was
performed in 32 CCl4 induced liver fibrosis SD rat models and 12 SD
rats of control group. Laboratory test related to liver function were done
before execution and liver was taken out for pathology evaluation. Liver
fibrosis was staged according to staging systems for rodents. Results showed
that T1rho could be used to diagnose early liver fibrosis (>F2) and correlation
was significant between T1rho values and both liver fibrosis stage and blood
serum parameters.Purpose
T1rho relaxation has been demonstrated
applicable on the diagnosis of liver fibrosis in rat models [1] and also on the diagnosis of human liver
cirrhosis by previous research studies[2,3]. But one recent study[4] found T1rho was a potential biomarker of liver
function instead of liver fibrosis. The purpose of this study is to find out
the relationship among T1rho, liver fibrosis stages and liver function in CCl4
induced liver fibrosis using rat models.
Methods
Liver fibrosis of different stages were induced by intraperitoneal
injection of 40% carbon tetrachloride (CCl4) with the dose of 2ml/kg,
twice a week in 41 male Sprague Dawley rats. Another 12 rats were injected the
same dose of saline. 5 to 6 rats of fibrosis group and 2 rats of control group
were scanned 1,2,4,6,8,10 weeks after the injection started. MRI scans
including T1rho imaging was performed on a PHILIPS 3.0T clinical scanner
(Achieva TX, Best, The Netherlands), with an animal coil. T1rho was performed
with a 3D fast field echo (FFE) sequence. Scan parameters were as follows: spin
lock time 0,10,20,40,60ms, spinlock frequency 500Hz, TR/TE 4.9ms/2.4ms, FOV 80mm×80mm×10mm, flip
angle 400, number of slices 5, NSA 4 respectively. T1rho images were fitted
using IDL (Research Systems, Inc., USA) on a pixel-by-pixel basis to the
exponentially decaying T1rho function to
generate the T1rho relaxation
map. Blood was drawn from right atrium before execution for a serum laboratory
test. Liver fibrosis of rats were staged according to the stage system for
rodents (F0~6), using pathological sections stained with Masson’s trichrome, picrosirius
red and hematoxylin and eosin.
Results
All rats in the control group survived and were staged
as F0. In the fibrosis group, 9 rats died, 32 rats were scanned and their
fibrosis stages were: F0=2, F1=5, F2=5, F3=5, F4=5, F5=5, F6=5. T1rho values of
the liver for F0~F6 were 40.68±1.60ms, 42.80±1.08ms, 44.98±1.04ms, 46.47±3.47ms, 47.73±3.84ms, 55.38±7.46ms and 57.08±5.11ms, respectively(Fig 1). Statistical
difference was found in the T1rho value among different fibrosis stage groups (P<0.001).
One-way ANOVA showed statistical differences between F0 and F2~6, F1 and F3~6, F2
and F5~6, F3 and F5~6, F4 and F5~6; no statistical differences were found
between F0 and F1, F1 and F2, F2 and F3~4, F3 and F4, F5 and F6. Correlation
was significant between T1rho values and liver fibrosis stage and correlation
coefficient was 0.883 (P<0.0001).
Of
all blood serum parameters, AST, ALT, ALP were found positively correlated with
both liver fibrosis stages and T1rho values; ALB was found negatively
correlated with both liver fibrosis stages and T1rho values. No significant
correlation was found between GLU, TBIL, T-CHO and T1rho values of the liver
and liver fibrosis stages (table 1).
Discussion
Prior research studies supposed T1rho was just
a potential biomarker for liver function, instead of a diagnosis method for
liver fibrosis [4]. Our research confirmed the value of T1rho in
the diagnosis of liver fibrosis in rat models. It could be used to diagnose
F2-6 liver fibrosis. We also uncovered that correlation was significant both between
T1rho values of liver and blood serum parameters and between liver fibrosis
stages and blood serum parameters, and the correlation coefficient between
liver fibrosis stages and blood serum parameters was usually higher. This may illustrate
that the pathology changes of liver fibrosis or liver cirrhosis lead to
abnormal liver function, which results in the changes in blood serum
parameters. But as blood serum parameters are indirect biomarkers of liver
fibrosis and could be affected by many other factors, it’s unstable compared
with T1rho. We could also get images of whole liver by using T1rho scan instead
of only numbers.
Conclusion
T1rho could be use to diagnose liver fibrosis, and it’s also a
potential biomarker of liver function.
Acknowledgements
No acknowledgement found.References
[1]. Wang YX,
Yuan J, Chu ES, et al. T1rho MR imaging is sensitive to evaluate liver
fibrosis: an experimental study in a rat biliary duct ligation model. Radiology
2011;259:712-9.
[2]. Rauscher I, Eiber M, Ganter C, et al.
Evaluation of T1rho as a potential MR biomarker for liver cirrhosis: Comparison
of healthy control subjects and patients with liver cirrhosis. European journal
of radiology 2014;83:900-4.
[3]. Allkemper T, Sagmeister F, Cicinnati V, et al.
Evaluation of fibrotic liver disease with whole-liver T1rho MR imaging: a
feasibility study at 1.5 T. Radiology 2014;271:408-15.
[4]. Takayama Y, Nishie A, Asayama Y, et al. T rho
Relaxation of the liver: A potential biomarker of liver function. Journal of
magnetic resonance imaging : JMRI 2014.