The Relationship Between Liver Function And Liver Parenchymal Contrast Enhancement On Gd-BOPTA-enhanced MR Imaging In The Hepatocyte Phase

Objectives:The hepatic function reserve is one of the most important parameters to assess prior to hepatic surgery. An insufficient hepatic function of the remnant hepatic parenchyma is one of the main contributing factors to the postoperative mortality in hepatic resection. Estimation of liver function is essential for preventing postoperative hepatic failure and for the clinical management of patients with liver cirrhosis. Liver function is usually evaluated by measuring the levels of biochemical parameters in the blood, such as bilirubin, albumin and coagulation factors, or by the Child-Pugh Class, using a combination of five factors (serum bilirubin and albumin levels, prothrombin activity, ascites levels, and the presence or absence of hepatic encephalopathy), which is commonly used to determine the prognosis of liver cirrhosis. The measurements of liver biochemical parameters are all only indirect measurements of hepatocyte function. Bilirubin levels are related to hepatocellular excretory function, while albumin and prothrombin activity are related to synthetic function but not to uptake. The measurement of liver enzymes reflects an escape of these enzymes from the liver cells. Child-Pugh classification reflects global liver function. Hepatic parenchymal enhancement is often heterogeneous in patients with liver cirrhosis. When liver function is inhomogeneous, biochemical parameters or Child-Pugh classification can occasionally be inadequate for estimating residual liver function. Recently, due to technical advances in the MRI and contrast agent fields, gadoxetic acid disodium (Gd-EOB-DTPA), a hepatocyte-specific MR contrast agent, which is gradually taken up by functional hepatocytes and excreted into bile, has been used to investigate the correlation between the clinical factors and hepatic enhancement in the hepatocyte-phase (the delay phase), as well as to evaluate the hepatic enhancement effects in normal and cirrhotic livers, therefore to assess liver function.Similar to Gd-EOB-DTPA, gadobenate dimeglumine (MultiHance, Gd-BOPTA), another hepatocyte-specific MR contrast agent with the dual properties of an extracellular agent and a hepatobiliary contrast agent, could display liver parenchymal enhancement at the hepatocyte-phase. Although the hepatobiliary phase is later and the relative biliary excretion is lower for GD-BOPTA than Gd-EOB-DTPA, equal hepatic parenchymal enhancement in the hepatocyte-phase was observed on T1-weighted images after the intravenous administration of the two contrast agent respectively. A study with experimental animal models reported the possible usefulness of Gd-BOPTA-enhanced MRI imaging for estimating the liver function. Accordingly, Gd-BOPTA enhanced MR imaging at the hepatocyte-phase may have the potential to assess liver function in human. Compared to Gd-EOB-DTPA, Gd-BOPTA is cheaper and it has a better vessel enhancement. However, to the best of our knowledge, almost all previous papers on liver function and MRI have used Gd-EOB-DTPA, and fewer studies have focused on Gd-BOPTA. In addition, in our clinical practice, we often encounter insufficient liver parenchymal Gd-BOPTA-enhanced MR hepatocyte-phase images in dysfunction patients, especially liver cirrhosis patients. Inadequately enhanced hepatocyte-phase images can impair detection or characterization of focal liver lesions due to decreased lesion-to-liver contrast. Therefore, it is important to identify the relationship between insufficient hepatic parenchymal contrast enhancement of Gd-BOPTA enhanced MR imaging in hepatocyte-phase and liver dysfunction.The purpose of this study was to investigate the relationship between liver function parameters and the degree of hepatic enhancement of gadobenate dimeglumine enhanced MR imaging at the hepatocyte-phase, as well as to clarify whether Gd-BOPTA enhanced MR imaging can evaluate liver function and liver function reserve.Materials and methods:This retrospective study was approved by the ethics committee of our hospital. From July 2012 to May 2014,278 consecutively registered patients with suspicious focal liver lesions or chronic liver diseases underwent hepaticGd-BOPTA-enhanced MR imaging in our hospital. Among them, we retrospectively identified 247 patients who underwent biochemical tests for the total bilirubin (T-bil), serum albumin (Alb), and prothrombin time (PT) within 2 weeks before or after liver MRI examination. The remaining 97 patients were excluded based on the following criteria:had undergone segmental liver resection, hemi-hepatectomy, biliary surgery, trans-arterial chemo-embolization, radiofrequency ablation, percutaneous ethanol injections, or chemotherapy before MR imaging (n=67); showed biliary dilatation, portal vein thrombosis, or a tumor larger than 10 cm in diameter (n=9); chronic liver disease, such as type B viral hepatitis, alcohol abuse or type C viral hepatitis, without clinical evidence of cirrhosis (n= 15); and abnormal liver function, such as fatty liver, liver metastasis or drug-induced liver injury, without cirrhosis (n= 6).Finally,150 patients (102 males and 48 females with a mean age of 66.35 years, range:37-85 years) were enrolled in our study. These included 73 with normal liver function without underlying chronic liver disease (group NLF) and 77 with liver cirrhosis. Patients with cirrhosis were classified into the following 3 groups according to the Child-Pugh classification:liver cirrhosis patients with Child-Pugh Class A (LCA group, n= 41), liver cirrhosis patients with Child-Pugh Class B (LCB group, n-25), liver cirrhosis patients with Child-Pugh Class C (LCC group, n= 11). Liver cirrhosis was diagnosed by imaging findings using MR imaging, computed tomography, or ultrasonography (irregularity of the liver surface, marginal dullness, atrophy of the liver right lobe, swelling of the left lobe, splenomegaly, and development of the collateral veins) for all patients.The MRI examination was performed on a 3-T system (Magnetom Verio; Siemens, Erlangen, Germany) with a phased-array body coil. The standard sequences performed before Gd-BOPTA administration were T1-weighted in-phase and T1-weighted out-of-phase imaging, respiratory triggered fat-suppressed turbo spin-echo T2-weighted, and diffusion weight imaging. Then, a transverse T1-weighted volume interpolated breath hold examination (T1-vibe) sequence with fat suppression was acquired before and after contrast media injection in the arterial phase, late arterial phase, portal venous phase, and hepatocyte-phase (90min). Two radiologists with 17 and 10 years of abdominal radiology experience, who were blinded to the clinical data, reviewed the MR images retrospectively. T1-vibe images at the precontrast and hepatocyte-phase were evaluated. These images were displayed with the same window width (500) and window level (250). They drew the regions of interest (ROIs) by consensus to measure signal intensity (SI) of liver parenchyma. The ROIs were placed at 2 locations in the left lobe (lateral and medial segments) and 2 locations in the right lobe (anterior and posterior segments). ROIs of identical size and shape were placed at the same locations in the two phases. Great care was taken to avoid focal hepatic lesions (e.g., hepatocellular carcinoma, hemangioma, cysts, etc.), imaging artifacts, and major branches of the portal or hepatic veins. Each ROI was a circle or oval (the size of the ROI ranged between 1.0 cm2 and 3.5 cm2). The average value of the four SIs of the liver parenchyma was used for data analysis. The relative enhancement ratio (RE) of the liver parenchyma was calculated from SI measurements before (SI pre) and 90 min after (SI post) the intravenous administration of Gd-BOPTA using the following formula:RE= (SI post-SI pre)/ SI pre.Pearson correlation analysis was used to evaluate the relationship between the REs and serum parameters, such as the total bilirubin, albumin and prothrombin time. One-way analysis of variance (ANOVA) was used to analyze differences in the REs of the liver parenchyma between the NLF, LCA, LCB, and LCC groups. Post hoc pair-wise comparisons were performed with the Tukey procedure. All tests were two-sided and values of p< 0.05 indicated a significant difference. All statistical analyses were performed with SPSS Statistics (version 14.0, Chicago, IL, USA). Results:There were negative correlations between the REs of the hepatic parenchyma and the T-bil (r=-0.263, P< 0.01) and PT (r=-0.24, P< 0.01); there was a positive relationship between the REs of the hepatic parenchyma and Alb (r= 0.328, P<0.01).The RE of the liver parenchyma in the NLF group was significantly higher than that of the LCB group (0.46±0.19 versus 0.30±0.14, p< 0.001) and the LCC group (0.21±0.11, p< 0.001). The RE of the liver parenchyma in the LCA group was significantly higher than that of the LCB group (0.44±0.14 versus 0.30±0.14, p< 0.001) and the LCC group (0.21 ±0.11, p< 0.001). No significant differences were observed between the NLF and LCA groups (p= 0.504), between the LCB and LCC groups (p= 0.922), with respect to the REs of the liver parenchyma.Conclusion:This present study clearly demonstrated the good correlation between GD-BOPTA enhanced MR imaging at hepatocyte-phase and liver function parameters such as total bilirubin, albumin, prothrombin time, and Child-Pugh Class. Because the intracellular uptake of Gd-BOPTA decreases with impaired liver function, the measurement of the degree of liver parenchymal contrast enhancement of GD-BOPTA enhanced MR imaging at the hepatocyte-phase may be a non-invasive technique with a great potential to semi-quantitatively assess liver function and liver function reserve.