Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose,double dose or half-dose contrast enhanced imaging

Introduction

Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC).

Materials and methods

30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w ± IR) were acquired 20–30 min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann–Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated.

Results

All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference.

Conclusions

Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR.     

MR imaging in patients with suspected liver metastases: value of liver-specific contrast agent Gd-EOB-DTPA.

The appropriate staging of malignant tumors is increasingly important as new therapeutic strategies develop. Because metastatic involvement of the liver in extrahepatic malignant disease may significantly change therapeutic approach, it is important to rule out such involvement with high confidence. Moreover, the differentiation between incidental benign lesions, such as hemangioma, focal nodular hyperplasia (FNH), or adenoma, is of high interest. Magnetic resonance (MR) imaging has proved reliable for diagnostic work-up of the liver. Liver-specific contrast agents have been especially helpful in detecting and precisely characterizing focal liver lesions, but the use of these agents has been limited because it has not been possible to perform both proper vascular phase and liver-specific phase within a reasonable time frame and in a single examination after a single injection of contrast agent. However, the hepatobiliary contrast agent gadolinium-ethoxybenzyl (Gd-EOB)-DTPA now allows combined dynamic imaging and hepatocyte-specific imaging in one examination. Gd-EOB-DTPA can be injected as a bolus and shows the enhancement characteristics and vascularity of liver lesions. In the delayed phase, which is acquired most appropriately 20 min after injection, Gd-EOB-DTPA is taken up selectively by functioning hepatocytes. Thus, malignant liver lesions, e.g. metastases, are spared from contrast uptake of the surrounding liver parenchyma. These lesions are hypointense in contrast to the surrounding bright liver. We review the current literature and present a practical approach to Gd-EOB-enhanced MR imaging using imaging examples of patients with liver metastases.     

Contrast-enhanced MR cholangiography: comparison of Gd-EOB-DTPA and Mn-DPDP in healthy volunteers

Objective The purpose of this study was to compare the biliary enhancement dynamics of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) and mangafodipir trisodium (Mn-DPDP) for contrast-enhanced MR cholangiography (MRC) in healthy subjects. Methods 15 healthy volunteers underwent MRI at 1.5 T with volumetric interpolated breath-hold examination sequence. Each volunteer was scanned once for each contrast agent. The signal-to-noise ratio (SNR) of the liver parenchyma and common hepatic duct (CHD) and the contrast-to-noise ratio (CNR) of CHD to liver parenchyma were evaluated and compared before and at several time points (5, 15, 30, 45, 60, 90, and 120 min) after injection of each agent. Results SNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP in liver parenchyma after 5 min and in CHD after 15 min (p<0.05). CNR of CHD to liver parenchyma using Gd-EOB-DTPA showed an initial decrease at 5 min post-injection followed by a steep increase to a peak at 15 min post-injection. CNR using Mn-DPDP showed a steady increase to a peak at 15 min post-injection without an initial decrease. At 15 min, the value of CNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP (p<0.05). Conclusion For both contrast agents, CNR reached a peak at 15 min after contrast injection. At this time point, CNR of Gd-EOB-DTPA was significantly higher than that of Mn-DPDP. Therefore, Gd-EOB-DTPA may provide better contrast-enhanced MRC than Mn-DPDP at 15 min after contrast administration.     

磁共振胆道造影在胆道梗阻定位和定性诊断中的价值

目的：通过ＭＲＩ胆道造影（ＭＲｃｈｏｌａｎｇｉｏｇｒａｐｈｙ，ＭＲＣ）与ＣＴ、ＵＳ、经皮穿刺胆道造影术（ＰＴＣ）或内窥镜逆行胰胆管造影术（ＥＲＣＰ）及手术、病理的对照研究，评价ＭＲＣ显示胆道梗阻部位，确定梗阻原因的能力。材料与方法：３０例梗阻性黄疸的患者在ＧＥＳｉｇｎａ１．５Ｔ超导系统上进行了ＭＲＣ检查，并与ＰＴＣ或ＥＲＣＰ、ＣＴ、ＵＳ、手术及病理对照。结果：本组资料中，ＭＲＣ显示胆道梗阻的部位准确性达１００％，优于有损伤性的ＰＴＣ或ＥＲＣＰ。ＭＲＣ确定梗阻原因的准确性达７０％，类似于ＰＴＣ或ＥＲＣＰ、ＣＴ、ＵＳ。结论：初步研究结果表明，无损伤性的ＭＲ胆道造影在梗阻性黄疸的定位和定性上具有很高的敏感性、准确性，对于梗阻性黄疸，特别是行ＥＲＣＰ失败和不宜行ＰＴＣ或ＥＲＣＰ的病人是最有效的替代方法。     

Optimal dose of hepatobiliary contrast agent for MR cholangiography: Experimental study in rats

The purpose of this study is to clarify the optimal dose of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) for cholangiography in conventional T1-weighted imaging. We divided 30 rats into three dose groups (3, 10, and 30 μmol/kg). For the in vitro study, we collected bile and measured the concentration of gadolinium in bile after Gd-EOB-DTPA injection. T1-weighted images of the collected bile were obtained for measurement of signal intensity. For the in vivo study, we obtained T1-weighted images before and after injection and evaluated bile duct/liver contrast by the signal intensity ratio and visual assessment of the images. The gadolinium concentration had an early peak; however, the signal intensity of the bile had a later peak because of the high gadolinium concentration during the early phase, which induced a T2-shortening effect. Optimal bile duct/liver contrast was obtained in the 10-μmol/kg groups at all time points. We conclude that the optimal dose of Gd-EOB-DTPA for MR cholangiography in rats is 10 μmol/kg, one-third of the dose used in liver imaging.     

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.     

MR prediction of liver fibrosis using a liver-specific contrast agent: Superparamagnetic iron oxide versus Gd-EOB-DTPA

Purpose:

To examine whether the uptake of a liver‐specific contrast agent in the liver parenchyma was correlated with the degree of liver fibrosis.

Materials and Methods:

This retrospective study included 54 and 63 patients who underwent superparamagnetic iron oxide (SPIO)‐ and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced MRI before liver surgery, respectively. For each patient, we calculated ΔR2* and ΔR2, which represent differences in R2* and R2 values of the liver parenchyma before and after administration of SPIO; and the increase rate of liver‐to‐spleen signal intensity ratio (LSR) on the hepatobiliary phase compared with the precontrast image. The correlation of each MR parameter with the degree of liver fibrosis (F0 to F4) was assessed using Spearman's rank correlation test.

Results:

The increase rate of LSR was best correlated with the degree of liver fibrosis and significantly decreased as the liver fibrosis progressed (rho = ?0.641; P < 0.0001). It showed sensitivity of 76.9% and specificity of 83.3% in differentiating F3 or greater fibrosis when 1.126 or less was set up as a cut‐off value. No significant correlation was obtained between ΔR2* or ΔR2 and the degree of liver fibrosis.

Conclusion:

The uptake of Gd‐EOB‐DTPA in the liver parenchyma decreased as the liver fibrosis progressed. J. Magn. Reson. Imaging 2012;36:664–671. © 2012 Wiley Periodicals, Inc.

     

A multinuclear MR study of Gd-EOB-DTPA: Comprehensive preclinical characterization of an organ specific MRI contrast agent

The characterization of the hepatobiliary contrast agent Gd-EOB-DTPA (gadolinium 3, 6, 9-triaza-3, 6, 9-tris(carboxymethyl)-4-(4-ethoxybenzyl)-undecandicarboxylic acid) in various media (water solution, protein containing solution, phosphorylated metabolites solution, and excised and perfused liver) was performed using different NMR approaches: water ¹H nuclear magnetic relaxation dispersion profiles, ²H NMR longitudinal and transverse relaxation rates of labeled complex, water ¹⁷O transverse relaxation rates and chemical shifts, ³¹P relaxation rates and peak area of phosphorylated metabolites. The higher proton relaxivity of Gd-EOB-DTPA in water compared with Gd-DTPA is related to a shorter distance (r) between the water proton and the gadolinium ion and to a longer rotational correlation time (T_R) of the hydrated complex. Although the thermodynamic stability of Gd-EOB-DTPA is identical to the one of Gd-DTPA, its kinetic stability in solutions containing phosphorylated metabolites (ATP, phosphocreatine, and inorganic phosphate) as measured by ³¹P relaxation rates analysis is higher than for the parent compound. Gd-EOB-DTPA binds noncovalently to serum proteins. Its interaction with human serum albumin is characterized by a dissociation constant of 1-4.1 mM as calculated from proton and deuterium relaxation rates and equilibrium dialysis. This noncovalent interaction involves the subdomain IIA of human serum albumin. ³¹P spectroscopy of the excised and perfused rat livers was used to monitor the uptake of Gd-EOB-DTPA by the hepatocytes where it enhances the nuclear relaxation of the intracellular metabolites without impairing the adenosine triphosphate metabolism of the cells.     

Ablation of the cystic duct and gallbladder: clinical observations

The cystic duct and gallbladder were ablated in eight patients with acute gallbladder disease who had been treated with minicholecystostomy instead of cholecystectomy because of multiple risk factors. First, endoluminal transcatheter radio-frequency electrocoagulation of the cystic duct was performed under fluoroscopic control, which resulted in complete occlusion in all eight patients. Next, the mucosa of the isolated gallbladder was sclerosed with 95% ethanol and 3% sodium tetradecyl sulfate in one to four sessions; no analgesics were required. The gallbladder volumes of all patients, estimated by means of ultrasound, were 1.5-22 cm3 (average, less than 10 cm3) after a mean follow-up period of 5 months. One patient died of a cerebrovascular accident 15 months after sclerotherapy. In all surviving patients, the gallbladder fistulas are dry and obliterated. These early clinical data indicate that electrocoagulation permits reliable, safe obliteration of the human cystic duct. The authors believe that sclerotherapy of the isolated gallbladder is feasible without toxic effects but that their treatment needs adjustment to achieve complete ablation of the gallbladder mucosa in a shorter period and in all patients.     

Imaging characteristics of hepatocellular carcinoma using the hepatobiliary contrast agent Gd-EOB-DTPA

PURPOSE: To evaluate the ability of contrast-enhanced magnetic resonance imaging (MRI) with Gd-EOB-DTPA in comparison with non-enhanced imaging and spiral computed tomography (CT) to provide additional information for classification and characterization of hepatocellular carcinoma. MATERIAL AND METHODS: Forty patients with histopathology-proven hepatocellular carcinoma were selected for this subgroup analysis from a phase-III multicenter study in 235 patients with known or suspected liver lesions. The primary analysis was comparison of the proportion of hepatocellular carcinoma correctly classified and characterized by combined pre-/post-contrast MRI compared with pre-contrast MRI alone or with spiral CT. All images were evaluated on site, and in a blinded reading by three independent readers off site. RESULTS: In the on-site evaluation, the lesions were correctly classified as a malignant tumor with combined MRI in 90.3%, with pre-contrast imaging alone in 82.9% and with spiral CT in 87.8% (n.s.). The proportion of correct characterization (lesion type diagnosis) with combined MRI was 85.4%, 75.6% for pre-contrast imaging, and 77.5% for spiral CT (n.s.), respectively. In the blinded reading, one reader showed a significant increase in the proportion of correctly characterized lesions by 27% (P<0.05). The other two readers showed a reduction in the proportion of correct characterization by 12% and 15%, respectively (n.s.). CONCLUSION: With regard to lesion classification, no difference was found between combined pre-/post-contrast MRI and spiral CT. A non-significant trend in favor of Gd-EOB-DTPA-enhanced MRI with regard to characterization of hepatocellular carcinoma was found, although the CT scans were not optimized as the MRI scans.     

Study of clinical application of hepatic-biliary specific MR contrast agent (Gd-EOB-DTPA) in the diagnosis of focal hepatic lesions

目的:探讨Gd-EOB-DTPA MRI增强扫描时肝局灶性病变的表现及此新型对比剂的诊断效能,提高对肝脏局灶性病变的诊断准确性.方法:已知或怀疑为肝脏局灶性病变的34例患者共90个病灶,病灶性质依次为肝囊肿20个、肝细胞肝癌16个、胆管细胞癌1个、肝脏转移性肿瘤37个、肝血管瘤9个、退变结节1个、肝脏局灶性结节增生1个、肝细胞腺瘤1个、肝脏炎性病变3个及肝脏淋巴上皮瘤样癌1个.所有患者依次行MRI平扫(抑脂TSE T2 WI、抑脂3DVIBE、2D GRE T1 WI)、Gd-EOB-DTPA三期(动脉期、门脉期和平衡期)增强扫描(抑脂3D VIBE)及延迟20min肝实质期扫描(抑脂2D GRET1WI、抑脂TSE T2 WI、抑脂3D VIBE).测量并分析Gd-EOB-DTPA增强前后肝脏和病灶信号变化、病灶-肝脏对比噪声比绝对值(|CNR|)变化情况;并观察病灶Gd-EOB-DTPA增强扫描表现和特征.结果:Gd-EOB-DTPA增强后各期肝实质信号及病灶肝脏|CNR|均显著增加(P＜0.001).动脉期、门脉期和平衡期所有病灶符合应用常规含钆(Gd)对比剂时的强化表现和特征;延迟20min肝实质期扫描时,肝脏局灶性结节增生呈等信号—高信号.1个肝细胞肝癌呈相对高信号,其余肝囊肿、肝细胞肝癌、胆管细胞癌、肝脏转移性肿瘤、淋巴上皮瘤样癌、退变结节、肝细胞腺瘤、肝血管瘤和肝脏炎性假瘤等均呈相对低信号.结论:Gd-EOB-DTPA动态增强扫描与延迟肝实质期扫描联合应用,可以提供病变形态、血供、细胞来源及功能等更多相关信息,从而提高诊断信心及诊断准确性.     

New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer

Purpose: 
To evaluate the feasibility of using dynamic contrast-enhanced MR imaging with a new intravascular contrast agent in grading human breast cancer. Material and Methods: 
23 patients with 27 breast tumors (21 carcinomas and 6 fibroadenomas) were examined with dynamic MR imaging after administration of Clariscan, an iron oxide nanoparticle with large T1 relaxivity and a long plasma half life. A 3D T1-weighted gradient echo sequence with an acquisition time of 60 s was repeated at regular intervals of 3-5 min before and up to 1 h after injection of 2 mg/kg b.w. of Clariscan. The endothelial transfer constant, Kps, which reflects overall vascular permeability, and the fractional plasma volume, fPV, were estimated from time-intensity curves acquired from three separate regions of interest (ROIs): whole tumor, a permeability hot spot, and a blood volume hot spot. Kps and fPV were compared to the results of histologic tumor grading (Scarff-Bloom-Richardson, SBR) and microvascular density, MVD. Results: 
A statistically significant correlation between the MR-derived Kps parameters and the SBR score was obtained for the whole tumor ROI (R = 0.70), and for the permeability hot spot ROIs (R = 0.67). A correlation between fPV and SBR was detected for the blood volume hot spot ROIs (R = 0.48). There was no statistically significant correlation between Kps or fPV with MVD. Conclusion: 
The results support the hypothesis that dynamic MR with the intravascular contrast agent Clariscan may be used for non-invasive tumor grading.     

MRI动态增强扫描在乳腺良恶性病变中的诊断价值

目的:评价MRI动态增强扫描在乳腺良恶性病变中的诊断价值。方法:回顾性分析58例经病理证实的乳腺病变的MRI动态增强扫描强化形态及时间-信号强度曲线图表现。结果:良性病变共22例(纤维腺瘤8例,导管内乳头状瘤5例,乳腺囊肿5例,导管囊状扩张伴慢性炎症1例,囊性乳腺病3例);恶性病变共36例(浸润性导管癌28例,浸润性小叶癌3例,导管原位癌2例,浸润性乳头状癌2例,髓样癌1例)。恶性病变多表现为边缘毛刺、分叶征或边缘模糊,环状强化或不规则强化。良性病变多表现为边缘光滑整齐的均匀强化,其中5例囊肿无强化。其中形态学阳性预测值为89.47%,阴性预测值为90.00%,准确率为89.66%。强化表现阳性预测值为89.74%,阴性预测值为94.74%,准确率为91.38%。时间-信号强度曲线图:22例良性病变,13例(59.09%)表现为Ⅰ型,8例(36.36%)表现为Ⅱ型,1例(4.55%)表现为Ⅲ型;36例恶性病变,1例(2.78%)表现为Ⅰ型,9例(25.00%)表现为Ⅱ型,26例(72.22%)表现为Ⅲ型,阳性预测值为79.55%,阴性预测值为92.86%,准确率为82.76%。结论:乳腺MRI动态增强的形态学表现与时间-信号强度曲线图相结合,在良恶性病变的诊断与鉴别诊断中具有较高的价值。     

Functional MR cholangiography: diagnosis of functional abnormalities of the gallbladder and biliary tree

OBJECTIVE: Our objective was to describe the technique and utility of functional MR cholangiography (fMRC) in the evaluation of the gallbladder and biliary tree. CONCLUSION: FMRC has the potential to provide a comprehensive examination for the anatomic and functional assessment of the gallbladder and biliary tree. Complex anatomic abnormalities and functional disorders can be shown by fMRC, including biliary obstruction and extravasation.