Quantitative evaluation of liver function with MRI using Gd-EOB-DTPA

Objective: Gadolinium 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 Methods: Adult 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 (CCI4) 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 CCI4. 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 CCI4 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 x 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 CCI4 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. Results: Histopathologic 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 CCI4. The ALT and AST levels were significantly increased after the three weeks of CCI4 administration (p = 0.018). The ICG R15 values were 4.47±2.08% and 19.43±3.98% before and after three-week administration of CCI4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCI4 administration, the deconvoluted curve after CCI4 administration revealed less hepatocyte extraction efficiency with a mean value of 77.7±3.6. There was a significant correlation between the HEF and changes of the ICG R15 by the Pearson correlation coefficient assessment (correlation coefficient = -0.965, p = 0.000). Conclusion: The Gd-EOB-DTPA HEF could be calculated from deconvolution analysis of aortic and hepatic parenchymal time-intensity curves obtained by dynamic MRI. The Gd-EOB-DTPA HEF was well correlated with changes of the ICG R15, which is the most common parameter used in the quantitative estimation of the hepatic function. The Gd-EOB-DTPA HEF is a direct, noninvasive technique for the quantitative evaluation of liver function. It could be a promising alternative for the determination of noninvasive hepatic function in those patients with liver disease.