Quantitative Evaluation of Liver Function with MRI Using Gd-EOB-DTPA

Abstract

ObjectiveGadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection, Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreted via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis.Materials and MethodsAdult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCl4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCl4. At the end of experimental period, an observer "blinded" to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCl4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL of Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, TR/TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128×128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier transform technique to calculate the hepatic extraction fraction (HEF). The presence and type of hepatic injury were determined by the histopathologic examination and statistical analysis of the changes of the hepatic enzyme levels, the ICG R15 and Gd-EOB-DTPA HEF values between the time before and after CCl4 administration with Wicoxon signed rank test. Correlation between the Gd-EOB-DTPA HEF and the change of the ICG R15 were analyzed with Pearson's correlation coefficient.ResultsHistopathologic examination showed findings that were compatible with hepatic fibrosis caused by chronic liver injury. The initial blood biochemical studies before the administration of carbon tetrachloride showed that the mean AST and ALT levels were 39.8±5.2 IU/L and 59.1±11.7 IU/L, respectively. The AST and ALT levels increased to 138.4±50.5 IU and 172.0±71.6 IU/L, respectively, after the three week administration of CCl4. The ALT and AST levels were significantly increased after the three weeks of CCl4 administration (p = 0.018). The ICG R15 values w...

Liver parenchymal enhancement of hepatocyte‐phase images in Gd‐EOB‐DTPA‐enhanced MR imaging: Which biological markers of the liver function affect the enhancement?

“…In a liver with impaired function, the receptors on the hepatocytes surface might not work as well as the normal hepatocytes. Some preliminary research suggested that the enhancement of the liver and hepatic function have some relation each other (6,7,19).The results of this study show that only Child-Pugh classifications and ICG-R15s were significantly correlated with liver enhancement. It is clear that albumin and prothrombin activity did not correlate with liver enhancement because these parameters relate to synthesis.…”

“…Getting another perspective on our result, it can be said that Gd-EOB-DTPAenhanced MR imaging may be applied to evaluate hepatic function, especially for ''partial hepatic function,'' which can be used for prehepatectomy evaluation. Indeed, some preliminary studies were carried out using animal models to evaluate liver function (7,21). Our results point to a clear correlation between ICG-R15s and liver enhancement, and this should encourage researchers to use Gd-EOB-DTPA-enhanced MR imaging as a new test of hepatic function.…”

“…It is readily understood that insufficient liver enhancement is related to a patient's liver dysfunction (6,7). However, the factors that may predict enhancement of the liver on hepatocyte-phase images have not been thoroughly researched.…”

Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB-DTPA in healthy subjects

“…It has recently been found that Gd-EOB-DTPA-enhanced MRC gives added morphological information to conventional T2-weighted imaging (4). In a study on rabbits, Ryeom et al described a method for measuring the hepatic extraction fraction and reported a significant correlation with the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), which is an important clinical test for evaluating liver function (17). The authors discuss the potential of Gd-EOB-DTPA-enhanced liver examinations as "a direct, noninvasive technique for the quantitative evaluation of liver function."…”

Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis

“…Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has previously been used in animal models for the evaluation of hepatic function in various experimental settings, either using semi-quantitative parameters or using deconvolutional analysis (DA) [22][23][24][25]. In human studies, liver parenchymal enhancement after administration of Gd-EOB-DTPA has been shown to correlate with ICG clearance and with liver cirrhosis as assessed by the CPS [26,27], and subsequent biliary excretion has been shown to be delayed in patients with impaired liver function [28].…”