Ryeom, Hun-Kyu
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Kim, Seong-Hun
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Kim, Jong-Yeol
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Kim, Hye-Jeong
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Lee, Jong-Min
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Chang, Yong-Min
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Kim, Yong-Sun
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
,
Kang, Duk-Sik
(Department of Radiology, Kyungpook National University School of Medicine, Korea.)
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. Be...
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 were 4.47±2.08% and 19.43±3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 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).ConclusionThe 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 para
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 were 4.47±2.08% and 19.43±3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 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).ConclusionThe 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 para
5 Henderson JM Warren WD A method of measuring quantitative hepatic function and hemodynamics in cirrhosis: the changes following distal splenorenal shunt Jpn J Surg 1986 16 157 168 3488457
6 Hepner GW Vesell ES Quantitative assessment of hepatic function by breath analysis after oral administration of [14C] aminopyrine Ann Intern Med 1975 82 632 638 1200495
7 Vesell ES The antipyrine test in clinical pharmacology: conceptions and misconceptions Clin Pharmacol Ther 1979 26 275 286 111889
11 Berk PD Potter BJ Stremmel W Role of plasma membrane ligand binding proteins in the hepatocellular uptake of albumin-bound organic anions Hepatology 1987 7 165 176 3542777
12 Cherrick GR Stein SW Leevy CM Davidson CS Indocyanine green: observation on its physical properties, plasma decay, and hepatic extraction J Clin Invest 1960 39 592 600 13809697
13 Wolkoff AW The role of an albumin receptor in hepatic organic anion uptake: the controversy continues Hepatology 1987 7 777 779 3038726
14 Hashimoto M Watanabe G Hepatic parenchymal cell volume and the indocyanine green tolerance test J Surg Res 2000 92 222 227 10896825
15 Murase K Tsuda T Mochizuki T Ikezoe J Hepatic excretion fraction of hepatobiliary radiopharmaceuticals measured using spectral analysis Nucl Med Commun 1999 12 1041 1045 10572914
16 Tolia V Kottamasu SR Tabassum D Simpson P The use of hepatocyte extraction fraction to evaluate neonatal cholestasis Clin Nucl Med 1999 24 655 659 10478739
18 Proctor E Chatamra K Controlled induction of cirrhosis in the rat Br J Exp Pathol 1983 64 320 330 6882679
19 Bosma A Brouwer A Seifert WF Knock DL Synergism between ethanol and carbon tetrachlorid in the generation of liver fibrosis J Pathol 1988 156 15 21 3193297
20 McLean EK McLean AE Sutton PM Instant cirrhosis: an improved method for producing cirrhosis of the liver in rats by simultaneous administration of carbon tetrachloride and phenobarbitone Br J Exp Pathol 1969 50 502 506 5388497
21 Brandao CG Ferreira HH Piovesana H Development of an experimental model of liver cirrhosis in rabbits Clin Exp Pharmacol Physiol 2000 27 987 990 11117235
22 Schuhmann-Giampieri G Mahler M Roll G Maibauer R Schmitz S Pharmacokinetics of the liver-specific contrast agent Gd-EOB-DTPA in relation to contrast-enhanced liver imaging in humans J Clin Pharmacol 1997 37 587 596 9243351
23 Muhler A Oude Elferink RPJ Weinmann HJ Complete elimination of the hepatobiliary MR contrast agent in hepatic dysfunction: an experimental study using transport-deficient, mutant rats MAGMA 1994 1 134 139
24 Clement O Muhler A Vexler V Berthezene Y Brasch RC Gadolinium-ethoxybenzly-DTPA: a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats Invest Radiol 1992 27 612 619 1428739
25 Muhler A Clement O Saeed M Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects Invest Radiol 1993 28 26 32 8425849
26 Weinmann HJ Schuhmann-Giampieri G Schmitt-Willich H Vogler H Frenzel T Gries H A new lipophilic gadolinium chelate as a tissue-specific contrast medium for MRI Magn Reson Med 1991 22 233 237 1812351
27 Muhler A Heinzelmann I Weinmann HJ Elimination of gadolinium-ethoxybenzyl-DTPA in a rat model of severely impaired liver and kidney excretory function. An experimental study in rats Invest Radiol 1994 29 213 216 8169100
28 Hamm B Staks T Muhler A Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging Radiology 1995 195 785 792 7754011
29 Muhler A Freise CE Kuwatsuru R Acute liver rejection: evaluation with cell-directed MR contrast agents in a rat transplantation model Radiology 1993 186 139 146 8416555
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