Prolonged positive contrast enhancement with Gd-EOB-DTPA in experimental liver tumors: Potential value in tissue characterization

To evaluate the potential of the hepatobiliary magnetic resonance (MR) imaging contrast agent gadolinium EOB-DTPA (ethoxybenzyl diethylenetria-minepentaacetic acid) for the characterization of hepatic tumors, 79 primary and six implanted hepatomas in 38 rats were studied. MR imaging findings after administration of Gd-DTPA (0.3 mmol/kg) and Gd-EOB-DTPA (30 μmol/kg) were correlated with microangiographic and histologic findings. Gd-EOB-DTPA produced a strong liver enhancement, which caused prompt negative contrast enhancement (CE) in all implanted hepatomas and in 77 of 79 primary hepatomas. A positive CE that lasted up to 2 hours was found in two of 79 primary hepatomas, both of which were highly differentiated (grade I) hepatocellular carcinomas (HCCs). The rest were moderately differentiated to undifferentiated HCCs (grades II-IV). Rim enhancement, which corresponded histologically to peritumoral malignant infiltration sequestering normal hepatocytes, was seen around all implanted and some primary hepatomas. Positive tumor CE after administration of Gd-EOB-DTPA in this study is much less frequent but much more specific in comparison with the results of previous studies with manganese-DPDP (N, N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis[phosphate]). These findings may help further discriminate hepatic tumors.     

Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid interaction with clinical drugs in rats

RATIONALE AND OBJECTIVES: To investigate whether the hepatic enhancement characteristics of Gd-EOB-DTPA are influenced by the preapplication of a variety of commonly used clinical pharmaceuticals (eg, antibiotics, antineoplastic drugs, corticosteroids, antiarrhythmia drugs, antianxiety drugs, scopolamine, and xanthine derivatives). MATERIALS AND METHODS: Eleven commercially available drugs (prednisolone, rifampicin, doxorubicin hydrochloride, cisplatin, propranolol hydrochloride, scopolamine butylbromide, theophylline, ampicillin, cefotaxime sodium, verapamil hydrochloride, and diazepam) were intravenously (IV) injected in rats at three to five times the clinical dose (n = 3 or 6 per drug). A control group of rats was given saline (n = 6). Gd-EOB-DTPA (25 micromol Gd/kg IV) was administered to rats 30 minutes after the injections of the clinical drugs. Liver MR imaging was performed with a 2.0 T animal imager before and up to 60 minutes after injection. Enhancement (ENH) (%) and area under the data from time versus enhancement curve (AUD) were calculated. RESULTS Rifampicin was the only drug that significantly decreased the hepatic enhancement by Gd-EOB-DTPA. Both the maximum enhancement of the liver and the AUD were significantly reduced when rifampicin was preinjected. Preinjection of prednisolone, doxorubicin hydrochloride, cisplatin or propranolol hydrochloride yielded a slightly but significant increased maximum enhancement of the liver. Furthermore, the enhancement declined more slowly when these drugs were preadministered, yielding a large AUD. None of the other drugs showed a significant effect on hepatic enhancement. CONCLUSION: Rifampicin exerted a clinically significant decrease on hepatic enhancement by Gd-EOB-DTPA. Prednisolone, doxorubicin hydrochloride, cisplatin, or propranolol hydrochloride slightly but significantly increased the hepatic enhancement by Gd-EOB-DTPA.     

四氯化碳致肝纤维化动物模型实验条件的优化

目的优化四氯化碳（carbon tetrachloride,CCl4）肝纤维化动物模型的造模方法。方法对肝纤维化模型从CCl4剂量、造模途径和动物种属等方面进行优化。造模剂量优化时采用昆明小鼠,腹腔注射CCl40.5、0.75、1.0ml/kg,2次/周,共8周,于第9周开始停止注射CCl4,观察至第12周;造模方式优化时采用ICR小鼠,CCl4腹腔注射或灌胃,2次/周,共12周;动物种属优化时,选择ICR小鼠和SD大鼠,CCl4灌胃,2次/周,共12周。行苏木精-伊红染色和马松三色染色观察动物的肝脏病理学改变。结果选用不同剂量的CCl4腹腔注射后,在第10周,0.5ml/kgCCl4造模仅在汇管区形成纤维化,0.75ml/kgCCl4则形成了纤维间隔,而1ml/kgCCl4造模可以形成早期肝硬化,提示适当的CCl4剂量为1ml/kg。灌胃和腹腔注射的方式均能导致明显的肝纤维化,其中灌胃方式死亡率在10%以下,而腹腔注射方式造模死亡率在80%以上,提示灌胃造模动物耐受性较好。应用CCl4后,大鼠和小鼠肝纤维化的各指标变化趋势一致,大鼠变化更为明显。结论 CCl4致肝纤维化模型的建立宜采用1ml/kgCCl4灌胃的方法,可根据实验目的选用不同种属的动物。     

Gd-EOB-DTPA enhanced MRI of the liver: Correlation of relative hepatic enhancement,relative renal enhancement,and liver to kidneys enhancement ratio with serum hepatic enzyme levels and eGFR

Objectives

To assess the correlation of relative hepatic enhancement (RHE), relative renal enhancement (RRE) and liver to kidneys enhancement ratio (LKR) with serum hepatic enzyme levels and eGFR in Gd-EOB-DTPA enhanced MRI of the liver and to assess threshold levels for predicting enhancement of the liver parenchyma.

Methods

Data of 75 patients who underwent Gd-EOB-DTPA enhanced MRI of the liver were collected. Images were obtained before contrast injection, during the early arterial phase, late arterial phase, venous phase, delayed phase, and hepatobiliary phase which was 20 min after Gd-EOB-DTPA administration. Signal intensity of the liver and the kidneys in all phases was defined using region-of-interest measurements for relative enhancement calculation. Serum hepatic enzyme levels and eGFR were available in all patients. Spearman correlation test was used to test the correlation of RHE, RRE and LKR with serum hepatic enzyme levels and eGFR.

Results

In the hepatobiliary phase all serum hepatic enzymes were significantly correlated with RHE; total bilirubin (TBIL) and cholin esterase (CHE) showed strongest correlations. TBIL and CHE were significantly correlated with RRE in the arterial phases. TBIL and CHE were significantly correlated with LKR in the arterial phase and hepatobiliary phase. eGFR showed no correlation.

Conclusions

In Gd-EOB-DTPA enhanced MRI, TBIL and CHE levels may predict RHE, RRE and LKR.     

Contrast enhancement with GD-EOB-DTPA in MR imaging of hepatocellular carcinoma in mice: A comparison with superparamagnetic iron oxide

The purpose of this study was to evaluate the ability of the new liver-specific magnetic resonance contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) to detect hepatocellular carcinoma (HCC). Seventeen mice with 66 chemically induced HCCs underwent magnetic resonance imaging with both Gd-EOB-DTPA (30 μmol/kg) and superparamagnetic iron oxide (SPIO; 10 μmol/kg). After enhancement, lesion-to-liver contrast-to-noise ratios (CNRs) of 47 detected HCCs increased negatively from 3.7 ± 10.7 (mean ± SD) to –55.1 ± 25.8 with Gd-EOB-DTPA (P < .001) and increased positively from 10.4 ± 10.4 to 26.1 ± 16.3 with SPIO (P < .001). The improvement of CNR after administration of SPIO was less in smaller lesions (< 4 mm), whereas that after administration of Gd-EOB-DTPA was independent of lesion size. However, Gd-EOB-DTPA positively enhanced four HCCs (8.5%), both highly differentiated (grade 1) and moderately differentiated (grade 2). Gd-EOB-DTPA allows the conspicuous detection of small HCCs; however, moderately differentiated HCCs occasionally may be positively enhanced.     

肝脏MR动态增强扫描：Gd-EOB-DTPA与Gd-DTPA的个体内对照研究

目的：比较钆塞酸二钠（Gd-EOB-DTPA）及钆喷酸葡胺（Gd-DTPA）肝脏 MR动态增强扫描腹腔脏器及血管的强化特点,重点比较Gd-EOB-DTPA移行期与Gd-DTPA平衡期的图像特点。方法：本研究为前瞻性、个体内随机对照研究。25例病理证实为原发直肠癌或结肠癌、怀疑肝转移的患者,3天内行2次肝脏 MR 动态增强检查,分别使用 Gd-EOB-DTPA及Gd-DTPA两种对比剂。动态增强扫描的序列相同,包括平扫、动脉期、门静脉期、平衡期（Gd-DTPA）／移行期（Gd-EOB-DTPA）。图像客观评估中,测量各期相图像上血管及肝脾实质的信号强度。以椎旁肌肉的信号为参考,计算相对信号强度（RS）并比较两组间的差异,以及不同期相时肝实质RS的差异。主观评估：读片者主观评价增强扫描各期相图像上,主动脉、门静脉及肝静脉与肝实质的相对信号强度。结果：肝实质的RS：在动脉期Gd-DTPA 组明显高于Gd-EOB-DTPA组（t＝3．006,P＝0．005）;在门静脉期及平衡期／移行期,两组检查的差异无统计学意义（t＝1．788,P＝0．086;t＝0．781,P＝0．442）。Gd-EOB-DTPA检查时,门静脉期肝实质RS明显高于动脉期（t＝－3．014,P＝0．006）,移行期RS与门静脉期的差异无统计学意义。Gd-DTPA检查时,平衡期肝实质RS明显低于门静脉期（t＝5．827,P＝0．000）。主观评估：Gd-DTPA增强扫描平衡期图像上所有患者的主动脉、门静脉、肝静脉均为高信号（100％）;Gd-EOB-DTPA 增强扫描移行期图像上主动脉、门静脉、肝静脉均以低或等信号为主（84％,92％,92％）。结论：Gd-EOB-DTPA动态增强 MR 检查,肝脏实质在门静脉期及移行期呈持续强化,其移行期的图像特征与Gd-DTPA平衡期的图像特征有明显不同,在影像诊断时应予以关注。     

Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging

RATIONALE AND OBJECTIVES: To investigate the potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for the differential diagnosis of nonalcoholic steatohepatitis (NASH) and fatty liver (FL). METHODS: Twenty-one male rats were divided into 3 groups. Seven rats in the NASH group were fed a choline-deficient diet for 10 weeks, and the 7 rats in the FL group were fed a standard diet also containing 1% (wt/wt) orotic acid for 4 weeks. As a control, 7 rats were fed a standard diet. After the feeding period, all rats were subjected to contrast-enhanced dynamic and delayed MRI with a 2D-FLASH technique. Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected into the tail vein at 24-hour intervals. Signal intensities of the liver were measured for each MR image and the relative enhancement (RE) was calculated. In addition, the time of maximum RE (Tmax) and the half-life of RE (T1/2) in liver were compared. After MRI, the liver was histologically analyzed to evaluate steatosis, hepatitis, and fibrosis. RESULTS: Diffuse macrovesicular steatosis and severe fibrosis were observed in the NASH group, whereas diffuse microvesicular steatosis and rare fibrosis were observed in the FL group. Immediately after the Gd-DTPA injection, the RE in the liver of each group temporarily increased, and thereafter, rapid RE reduction was observed. However, a continuous increase and subsequent slow reduction of RE were induced after the Gd-EOB-DTPA injection. Although there was no difference between the Tmax and T1/2 of each group after the Gd-DTPA injection, Tmax and T1/2 of the NASH group were significantly prolonged in comparison with FL and control groups after the Gd-EOB-DTPA injection (P < 0.01). CONCLUSIONS: It was possible to differentiate NASH and FL by evaluating the SI time course on Gd-EOB-DTPA enhanced MRI.     

Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats.

OBJECTIVES. Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI. METHODS. Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel. RESULTS. In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second. CONCLUSIONS. Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions.     

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 (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.

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 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).

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.     

Dynamic MR imaging of liver metastases with Gd-EOB-DTPA

Purpose: To assess liver and lesion enhancements by dynamic MR imaging after bolus injection of the hepatobiliary contrast agent gadolinium ethoxybenzyldiethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) in patients with liver metastases and to compare the effect of different doses.Material and Methods: A randomized double-blinded trial with doses of 12.5, 25 and 50 μmol/kg Gd-EOB-DTPA was performed in 35 patients with liver metastases. Liver enhancement, tumor enhancement and liver lesion contrast-to-noise (C/N) ratios were calculated from breath-hold gradient echo images (100/5/80°) recorded precontrast and at different times up to 10 min postcontrast.Results: Normal liver showed a characteristic enhancement pattern, with a rapid enhancement in the first 45 s postcontrast and a slight but significant further increase up to 600 s. The initial enhancement in the lesions was also pronounced, but the enhancement was slightly decreased after 240 s postcontrast. At dose levels of 12.5 and 25 μmol/kg Gd-EOB-DTPA, C/N ratios significantly increased compared to baseline from 90 to 600 s. Postcontrast C/N-values obtained using 50 μmol/kg Gd-EOB-DTPA were not significantly increased, except for the examinations 480 s postcontrast.Conclusion: In liver metastases, C/N ratios obtained with doses of 12.5 and 25 μmol/kg Gd-EOB-DTPA were slightly superior to 50 μmol/kg Gd-EOB-DTPA. This finding is probably due to a more pronounced extracellular effect of the contrast medium at higher doses.     

MR T1ρ as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication

Objectives

Recently it was shown that the magnetic resonance imaging (MRI) T1ρ value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl₄) liver injury model, this study further investigated the merit of T1ρ relaxation for liver fibrosis evaluation.

Methods

Male Sprague-Dawley rats received intraperitoneal injection of 2?ml/kg CCl₄ twice weekly for up to 6?weeks. Then CCl₄ was withdrawn and the animals were allowed to recover. Liver T1ρ MRI and conventional T2-weighted images were acquired. Animals underwent MRI at baseline and at 2?days, 2?weeks, 4?weeks and 6?weeks post CCl₄ injection, and they were also examined at 1?week and 4?weeks post CCl₄ withdrawal. Liver histology was also sampled at these time points.

Results

Liver T1ρ values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl₄ insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1ρ. Liver T1ρ values decreased upon the withdrawal of the CCl₄ insult. Histology confirmed the animals had typical CCl₄ liver injury and fibrosis progression and regression processes.

Conclusions

MR T1ρ imaging can monitor CCl₄-induced liver injury and fibrosis.

Key Points

? MR T1ρ is a valuable imaging biomarker for liver injury/fibrosis. ? Liver T1ρ was only mildly affected by oedema and acute inflammation. ? Liver MR T1ρ decreased when liver fibrosis and injury regressed.     

福辛普利对大鼠肝纤维化的影响

目的 研究血管紧张素转换酶抑制剂福辛普利抗大鼠肝纤维化的作用.方法 雄性清洁级SD大鼠40只,随机分成5组:阴性对照组(n=5),腹腔注射植物油,每日单蒸水灌胃;模型组(n=5),腹腔注射CCl4,每日单蒸水灌胃;阳性对照组(n=10),造模方法同模型组,每日用秋水仙碱0.2mg/kg灌胃;福辛普利小剂量组(n=10)...     

Hepatobiliary enhancement with Gd-EOB-DTPA: comparison of spin-echo and STIR imaging for detection of experimental liver metastases.

Gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecandioic acid-disodium salt (EOB-DTPA) ethoxybenzyl is a new hepatobiliary magnetic resonance (MR) contrast agent with dual elimination: 75% through the liver and bile and 25% through the kidneys in normal rats. In this study, Gd-EOB-DTPA was evaluated in a rodent model of metastatic liver disease to measure both relative enhancement and lesion-to-liver contrast. A secondary goal was to compare the relative performance of spin-echo (SE) and short inversion time inversion-recovery (STIR) imaging to demonstrate enhancement with Gd-EOB-DTPA. After administration of 0.1 mmol of Gd-EOB-DTPA per kilogram, liver signal increased (positive enhancement) more than 200% with the use of the SE technique and declined (negative enhancement) by more than 80% with use of the STIR technique. Only minimal enhancement of implanted liver tumor was observed. Unlike the tumor, the gall-bladder and lumen of the duodenum were progressively enhanced over time. The lesion-to-liver contrast increased by approximately 500% with both the SE and STIR techniques after administration of Gd-EOB-DTPA.     

血管生成抑制剂烟曲霉素衍生物在介入治疗肝细胞癌实验中的应用

目的研究经肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂合成的烟曲霉素衍生物（TNP-470）治疗ACI大鼠肝细胞癌的疗效。方法在20只雄性ACI大鼠肝包膜下移植Morris Hepatoma3924A肝癌小瘤块（2mm^3），移植术后第13天时进行MR检查，测量肿瘤体积V1，第14天时，在荷瘤大鼠经胃十二指肠动脉逆行插管至肝动脉而采取以下介入治疗方案：治疗组：碘化油（0．1ml）＋丝裂霉素（0．1mg）＋TNP-470（5．0mg）（10只）；对照组：碘化油（0．1ml）＋丝裂霉素（0．1mg）（10只）。治疗后再次进行MR检查测量肿瘤体积V2，比较肝肿瘤体积变化（V2／V1）。结果治疗组和对照组大鼠经介入治疗前后的肝肿瘤平均体积分别为0．04cm^3和0．15cm^3以及0．04cm^3和0．34cm^3。治疗组和对照组肿瘤体积平均增长倍数（V2／V1）分别为4．11和9．14。与对照组相比，治疗组能明显抑制肝肿瘤体积的增长（P〈0．01）。结论在ACI大鼠肝细胞癌模型，采用肝动脉化疗栓塞术结合肝动脉灌注血管生成抑制剂TNP-470的治疗方法可明显抑制肝肿瘤体积的生长。     

Biliary imaging with Gd-EOB-DTPA: is a 20-minute delay sufficient?

RATIONALE AND OBJECTIVES: The authors performed this study to quantitate the change in intrabiliary signal intensity 20 minutes after gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) injection and to correlate the degree of biliary visualization with changes in biliary signal intensity. MATERIALS AND METHODS: Sixteen patients with known hepatic masses (without known biliary disease) who were candidates for resection were enrolled in an open-label protocol of Gd-EOB-DTPA. Three-dimensional spoiled gradient-echo magnetic resonance (MR) images obtained in the coronal plane with breath holding before and 20 minutes after Gd-EOB-DTPA made up the biliary MR cholangiogram study. Manually defined regions of interest were used to measure signal intensity in the bile ducts before and after contrast material administration. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated. Biliary visualization was qualitatively assessed by using a five-point scale. RESULTS: The SNR and CNR significantly increased (P < .0002) after the administration of contrast material. Average biliary visualization ratings were excellent, with moderate to excellent interobserver agreement. There was no correlation between measured SNR or CNR and visualization ratings. CONCLUSION: A 20-minute delay after Gd-EOB-DTPA administration appears to be sufficient for adequate biliary enhancement. Residual hepatic enhancement does not appear to interfere with biliary visualization.     

Time-intensity curve in the abdominal aorta on dynamic contrast-enhanced MRI with high temporal and spatial resolution: Gd-EOB-DTPA versus Gd-DTPA in vivo

Purpose

To evaluate the difference in the time-intensity curves (TICs) of the abdominal aorta on dynamic contrast-enhanced MRI (DCE-MRI) between Gd-DTPA and Gd-EOB-DTPA.

Materials and methods

Ten healthy volunteers underwent DCE-MRI three times with the following protocol: group A, Gd-DTPA at an injection rate of 3 ml/s; group B, Gd-EOB-DTPA, 3 ml/s; group C, Gd-EOB-DTPA, 1.5 ml/s. Signal intensities (SIs) of the abdominal aorta were measured, and the contrast enhancement ratio (CER) was calculated. Time-to-CER curves were compared among the three groups. The differences in maximum CER (CER_max) and time-to-peak of CER were analyzed.

Results

The time-to-CER curve showed a double peak pattern in group A and single-peak pattern in groups B and C. The mean time between the first and the second peak was 6.2 s. The mean CER_max of each group was 4.50, 4.52 and 4.27, respectively. In group A, B and C, the mean time-to-peak was 14.6, 10.6 and 12.6 s, respectively. There was a significant difference between group A and B (P < 0.01).

Conclusion

To set up the optimal protocol for abdominal DCE-MRI, it should be noted that TIC in the Gd-DTPA and Gd-EOB-DTPA group showed different patterns, and a slower injection rate showed a less abrupt SI change in the Gd-EOB-DTPA group than in the Gd-DTPA group.     

Gd-EOB-DTPA enhancement pattern of hepatocellular carcinomas in rats: Comparison with Tc-99m-IDA uptake

The enhancement pattern of chemically induced hepatocellular carcinomas (HCCs) after intravenous administration of the hepatobiliary magnetic resonance (MR) contrast agent gadolinium-EOB-DTPA (ethoxybenzyl-diethylenetriaminepentaacetic acid) was compared with the uptake pattern of technetium-99m-labeled iminodiacetic acid (IDA), a hepatobiliary radioactive tracer. The hepatocyte uptake of both the contrast agent and the scintigraphic agent has been shown to be driven by the organic anion transporter. The tumors enhanced less than the liver after Gd-EOB-DTPA administration, whereas the Tc-99m-IDA uptake of differentiated HCCs exceeded that of the liver at 30 minutes and 3 hours after administration. The enhancement pattern of a differentiated HCC with Gd-EOB-DTPA does not mirror that seen with Tc-99m-IDA.     

MSCT肝脏增强扫描中的碘对比剂应用研究

目的:探讨MSCT肝脏增强扫描中碘对比剂浓度及注射速率对肝脏强化效果的影响。方法:90例受检者按对比剂碘浓度300mg/ml、350mg/ml、370mg/ml及注射速度3.0ml/s、4.0ml/s、5.0ml/s分成9组,各10例,保持每位检查者碘总量一致,即390mgI/kg体重。90例受检者均使用Siemens Somatom definition螺旋CT和Medrad Stellant双筒高压注射器行肝脏动态增强扫描。双盲式观察、分析肝脏峰值时间(Time to Peak)及强化峰值(Peak Contrast Enhance-ment)。结果:随着对比剂注射速度的增加肝脏各期峰值时间提前、强化峰值增高;对比剂碘浓度的增加肝脏强化各期峰值时间亦提前,但峰值变化不大,高浓度对比剂较低浓度肝脏强化峰值相近。结论:不同碘对比剂的浓度、注射速度对肝脏强化程度存在影响,低浓度对比剂、高速率注射、个性化给药可以得到满意的强化效果。     

New proposal for the staging of nonalcoholic steatohepatitis: Evaluation of liver fibrosis on Gd-EOB-DTPA-enhanced MRI

Purpose

We investigated whether the gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was useful for nonalcoholic steatohepatitis (NASH) staging based on the severity of liver fibrosis.

Materials and methods

Twenty-one male Sprague-Dawley rats aged 7 weeks, weighing about 150 g in NASH group were fed a choline-deficient diet for 4, 7 or 10 weeks, and seven rats in the control group were fed a standard diet (n = 7). After the feeding period, the rats were subjected to contrast-enhanced MRI (2D-FLASH; TR/TE = 101/2.9 ms, flip angle 90°). Gd-DTPA (0.1 mmol Gd/kg) and Gd-EOB-DTPA (0.025 mmol Gd/kg) were injected at 24-h intervals, and the speed of contrast injection was 1 mL/s. Signal intensities of the liver were measured and the relative enhancement (RE), the time of maximum RE (T_max) and elimination half-life of RE (T_1/2) in the liver were compared. The fibrosis rate (%) was calculated with the following formula: fibrosis/whole area × 100.

Results

The fibrosis rates of each group were as follows: 0.52, 0.79, 2.84, and 0.50% (4, 7, 10 weeks and control groups). The fibrosis rate of the 10 weeks group was significantly higher than the control and 4 or 7 weeks groups. Although there was no difference between the T_max and T_1/2 of each group after Gd-DTPA injection, the T_max and T_1/2 of the 10 weeks group were significantly prolonged in comparison with the control and 4 or 7 weeks groups after Gd-EOB-DTPA injection (p < 0.01). There was a significant correlation between the fibrosis rate and T_max or T_1/2 after Gd-EOB-DTPA injection (r = 0.90 or 0.97).

Conclusion

It was possible to assess the progress of liver fibrosis in NASH by evaluating the signal intensity-time course on Gd-EOB-DTPA-enhanced MRI.     

Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system.

Gadolinium diethylenetriaminepentaacetic acid (DTPA) covalently linked to the lipophilic ethoxybenzyl moiety (Gd-EOB-DTPA) was designed for use as a contrast agent in hepatobiliary magnetic resonance imaging. With T1 relaxivity values of 8.7 L/mmol.second in plasma and 16.6 L/mmol.second in rat liver tissue and a median lethal dose of 10 mmol/kg when administered intravenously in mice and rats, Gd-EOB-DTPA has a fairly high margin of safety. In rats and monkeys, biodistribution studies performed 7 days after administration of 0.25 mmol/kg revealed very little retention of gadolinium (less than 1%) in the tissues, indicating complete elimination via renal and biliary excretion. Biliary excretion was inhibited by coadministration of sulfobromophthalein, indicating the involvement of a carrier-mediated transport system based on the enzyme glutathione-S-transferase. In rats, the biliary transport maximum was 5 mumol gadolinium/min.kg. High T1 relaxivity of Gd-EOB-DTPA in rat liver in vivo can be explained by transient interaction with intracellular components and by increased microviscosity inside the hepatocyte.