As we all know, cirrhosis can cause damage to liver cells, increased spleen volume, and portal hypertension and so on, so we mainly involved the liver, spleen and portal vein. Our research was conducted at the HBP 15 min, we believed that this period could meet the needs for diagnosis of liver diseases and shorten the examination time of patients.
The signal intensity of liver parenchyma, spleen and portal vein
Liver parenchyma SI can be used to estimate liver function has been widely described, the way it works: the hepatobiliary phase of Gd-EOB-DTPA was made by the selective uptake of membrane-bound organic anion transporters (OATP1 B1/B3) [19–21]. Normal hepatocytes could use these transporters to ingest Gd-EOB-DTPA and the amount of Gd-EOB-DTPA reached the peak on the HBP 20 min; the impaired amount and functional capacity of these transporters could reduce the uptake of Gd-EOB-DTPA into hepatocytes [22], subsequently affected the liver signal. Our data shown that liver parenchyma SI gradually decreases with the increase of liver function damage, Previous studies [22–24] have also proved that the severity of cirrhosis can significantly affect the absorption of gadolinium, and then affect the degree of liver enhancement, which was consistent with our research.
The spleen does not contain hepatocytes, Gd-EOB-DTPA only shows the characteristics of non-specific extracellular space contrast agent. Our research indicates that the SI of spleen cannot reflect liver function and the mean value of spleen signals are equally likely in each group. In addition, we found most of the cases in all our groups, the spleen signal increased gradually from inside to outside for MR images whether pro-enhanced or HBP 15 min (Fig. 4), leading to an increase in the mean signal value of the spleen. We don't know how to explain this phenomenon, it may be related to the uneven magnetic field or the hemodynamics of the spleen.
In our study, portal vein SI constantly and slightly increased from normal to Child–Pugh class C, but there was no difference among groups, Zhang reported that LPC can efficaciously indicate the severity of liver function [10], their data on portal vein SI is similar to our research. Previous one has suggested that the delayed hyperintense portal vein sign can potentially be used to reflect hepatobiliary function [15], their subjects are mostly patients with extrahepatic cholestasis, we think that's the main reason for the difference. Study proved hepatic uptake and biliary elimination of bilirubin compete against Gd-EOB-DTPA, hyperbilirubinemia will lead to decreased absorption and clearance of Gd-EOB-DTPA, it also leads to delayed the contrast agent to stay in the blood for longer [25]. However, we hold that the bilirubin level in patients with cirrhosis may not be as high as that in patients with extrahepatic cholestasis, and hepatocytes may be able to meet this competition in patients with cirrhosis.
LPC, LSC and PSC
Different from enhanced CT, the signal intensity of MRI enhancement has a nonlinear relationship with the concentration of contrast agent, most studies used reference tissue (spleen) to correct the liver signal [12–14]. As we have seen, only one literature has studied the relationship between LPC and LSC [16], their results showed that LPC was strongly correlated with LSC, and LPC of each group was lower than LSC, They owed it to the portal vein SI, which can represent a more consistent reflection of the blood pool than that of the spleen. Our research also shows a strong correlation between LPC and LSC among groups (Fig. 2), but LPC was greater than LSC. The reasons for this difference may be as follow: (1) The different causes might lead to the different patterns of uptake and excretion of Gd-EOB-DTPA. Our patients are mainly hepatitis B cirrhosis, their patients are mainly chronic liver disease; (2) The MRI device and imaging sequence are different.
As we all known, no one has studied PSC yet, our research suggests that PSC cannot reflect liver function in patients with cirrhosis. As discussed before, portal vein SI constantly and slightly increased from normal to Child–Pugh class C, but there was no difference among groups, and the mean value of spleen signals are equally likely in each group. It's possible that there's no difference in portal vein-to-spleen (PSC) among groups.
The correlation between laboratory markers and MRI date
Some studies used ICG to reflect liver function, because there was a direct correlation between ICG clearance and hepatocytes, which can provide more complete information on liver uptake and excretion function [26–28]. We did not carry out this test because of operational difficulties. we quantitatively analyzed the correlations between MRI date and the liver function parameters. In this study, the liver parenchyma SI, LPC and LSC were weak to moderate correlated with laboratory markers. Zhang also demonstrated that weak to moderate correlation was observed between LPC and laboratory markers [10], which was consistent with our research. We also found that the liver parenchyma SI, LPC and LSC were negatively correlated with hepatic function scoring systems (Child–Pugh score and MELD score), the correlation coefficient in order from the large to the small both are: LPC, LSC, and the liver parenchyma SI, the reason may be that the changing trend of portal vein signal makes LPC have a higher correlation with liver function.
Receiver operating characteristic analysis showed that the AUC in order from the large to the small are: LPC, LSC, and the liver parenchyma SI (0.892, 0.889, 0.836), but the difference of AUCs among LPC, LSC and the liver parenchyma SI were not significant. This illustrates that they have the same ability to identify group 1 and group 2.
These results suggested that the LPC might be a more useful alternative imaging biomarker for the evaluation of liver function than LSC and the liver parenchyma SI when the liver function test and hepatic function scoring systems is not readily accessible at the time of reviewing images. Takatsu found that LPC could be used as a substitute for LSC for a simple assessment of degree of hepatic contrast enhancement [16], this is consistent with our research. In addition, they also believed that LPC can be especially useful in cases of splenectomy and Gamna–Gandy bodies [16]. And yet, we thought this conclusion needed further verification because of few patients with splenectomy (n = 6), Gamna–Gandy bodies (n = 7), and these patients were not graded for liver function.
However, our study had several limitations. Firstly, the severity of cirrhosis was not grouped by liver biopsy. Secondly, we did not classify the causes of cirrhosis such as viral hepatitis, alcohol abuse, and so on. The different causes might lead to the different patterns of uptake and excretion of Gd-EOB-DTPA. Last, it was difficult to avoid selection bias because of the retrospective nature of this study. Taken together, further prospective and multi-center studies are needed.