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.     

Contrast-enhanced MR imaging of liver and spleen: First experience in humans with a new superparamagnetic iron oxide

The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 μmol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration. MR imaging at 1.5 T was performed before and 8 hours to 14 days after fast intravenous injection (500 μmol Fe/min) of the SPIO (six subjects per dose). Results of this phase I study demonstrate that SHU 555 A at a concentration of 0.5 mol Fe/L was well tolerated. A dose-dependent minor increase in activated partial thromboplastin time, which remained within the normal range, was seen. All doses of SPIO caused a signal loss in both liver and spleen (P <.05) with a spin-echo sequence (TR = 2,300 msec, TE = 45 msec). The signal losses in the liver 8 hours after contrast agent injection were 58%, 79%, 82%, and 87% for the 5, 10, 20, and 40 μmol Fe/kg doses, respectively. The corresponding signal losses in the spleen were 23%, 45%, 65%, and 78%, respectively. The doses that reduced signal intensity by half were 3.1 μmol Fe/kg for the liver and 12.8 μmol Fe/kg for the spleen. The results suggest that the new SPIO formulation is a safe and efficient MR contrast agent.     

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.     

Performance of Gd-EOB-DTPA and superparamagnetic iron oxide particles in the detection of primary liver cancer: A comparative study by alternative free-response receiver operating characteristic analysis

The performance of gadolinium-ethoxybenzyl-dieth-ylenetriaminepentaacetic acid (Gd-EOB-DTPA) and superparamagnetic iron oxide (SPIO) particles in detecting liver cancer was compared using alternative free-response receiver operating characteristic (AFROC) analysis, which allowed observers to indicate both the confidence level and the locations of all perceived abnormalities. Axial T1-weighted MR images (1.5 T) pre/post Gd-EOB-DTPA (25 μmol/kg) injection were obtained for 12 rats with chemically induced liver tumors (64 tumors). T2-weighted images (T2WI) were obtained pre/post SPIO (10 μmol/kg) injection for the same animal. Liver signal-to-noise ratio (SNR), tumor-liver contrast-to-noise ratio (CNR), and histopathologic sections corresponding to MR images were obtained. In AFROC, the location and the confidence level for each tumor were indicated independently on MR images by four radiologists. By plotting true-positive fraction and probability of false-positive per image, the area under the AFROC curve (A1) was estimated and statistically analyzed between each sequence. Either drug significantly improved tumor-liver CNR (P < .001) and tumor detection (diameter ≤ 6 mm; P < .05). Gd-EOB-DTPA significantly (P < .05) improved the A1 in T1WI. There was no A1 difference between T2WI + SPIO and T1WI + Gd-EOB-DTPA. Gd-EOB-DTPA-enhanced T1WI showed the same performance as SPIO-enhanced T2WI in detecting liver tumors.     

Spin-echo and dynamic gadoliniumenhanced flash MR imaging of hepatocellular carcinoma: Correlation with histopathologic findings

Evaluation of histologic subtype and degree of differentiation in hepatocellular carcinoma (HCC) is essential because it affects patient prognosis and treatment planning. To evaluate the histologic subtype of HCC with magnetic resonance (MR) imaging, conventional spin-echo and dynamic studies were correlated with histopathologic and angiographic findings in 72 HCCs. Dynamic MR imaging was performed with the fast low-angle shot (FLASH) technique after administration of gadopentetate dimeglumine. There was considerable overlap in signal intensity between various tumor grades on both T1- and T2-weighted images. On dynamic MR images, the peak contrast enhancement ratio correlated with tumor grade (well-differentiated, 29.5 ± 24.7; moderately differentiated, 63.5 ± 24.1; poorly differentiated, 86.9 ± 26.4) or degree of dilatation of the sinusoidlike vascular space between tumor cells. The maximum contrast-to-noise ratio in tumor (relative to surrounding liver) was achieved within 60 seconds in 45 HCCs (mostly of the trabecular or pseudoglandular type). Enhancement was slight or minimal in 17 tumors (mostly small, well-differentiated tumors). In 10 tumors, the degree of enhancement increased with time, with maximum enhancement in the delayed phase (most frequently in scirrhous HCC). These dynamic patterns correlated with angiographic findings. These data indicate that the degree and pattern of enhancement on dynamic MR images reflect tumor differentiation and architecture of HCC.     

Contrast-enhanced MR imaging of diffuse and focal splenic disease with use of magnetic starch microspheres

The diagnostic value of magnetic starch microspheres (MSM), a new superparamagnetic contrast agent, was studied in experimental models of diffuse and focal splenic disease in rats by means of ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Owing to small differences in unenhanced T1 and T2 values between diffuse lymphoma and normal spleen, MR imaging failed to distinguish tumor-bearing animals from control animals by signal-to-noise ratios (SNRs) obtained with T1- and T2-weighted spin-echo sequences. One hour after injection of 20 μmol/kg MSM, lymphomatous spleen showed significantly (P <.001) reduced enhancement relative to normal splenic tissue. As a result, animals with diffuse lymphoma (SNR: 10.3 ± 1.7) could be easily differentiated from control animals (SNR: 5.5 ± 0.6) on T2-weighted (TR msec/TE msec = 2,000/45) images. In focal splenic disease, MSM produced normal enhancement of nontumorous splenic tissue, whereas relaxation times of tumors were not different before and after contrast agent injection. On T2-weighted images (2,000/45), the tumor-spleen contrast-to-noise ratio increased from (4.8 ± 1.6 to 21.8 ± 1.9 +354%), improving conspicuity of splenic tumors. The results show that MSM-enhanced MR imaging improves the detection of diffuse and focal splenic disease.     

Enhancement effects of a hepatocyte receptor—specific MR contrast agent in an animal model

The enhancement characteristics of the liver and spleen produced by a hepatocyte-specific magnetic resonance imaging agent, an arabinogalactan-coated ultrasmall superparamagnetic iron oxide derivative, BMS 180550, were evaluated. Both heavily T1- and T2-weighted sequences were used. Imaging was performed in the farm pig model, as a function of contrast agent concentration (5, 10, and 20 μmol of iron per kilogram) and delay (immediate, 0.5, 2.5, 5.0, 7.5, and 9.0 hours) after bolus injection of BMS 180550. BMS 180550 provided excellent contrast enhancement characteristics by producing marked positive enhancement with T1-weighted sequences and marked negative enhancement with T2-weighted sequences. The T1-weighted enhancement immediately after contrast agent injection was of greater magnitude in the spleen (329% ± 83) than in the liver (66% ± 16). Postcontrast negative enhancement with T2-weighted sequences was largely hepatocyte specific at 5 and 10 μmol/kg but was also seen within the spleen at 20 μmol/kg. The authors discuss the possible mechanisms that produce these changes and conclude that 10 μmol/kg BMS 180550 is near the optimum dose for maximizing the enhancement properties of this agent with all sequences in the farm pig.     

Mn-DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 μmol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 μmol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occured at the 50 μmol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 μmol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%–137.5%) than the 50 μmol/mL formulation (46.2%–86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP–enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 μmol/kg Mn-DPDP at a concentration of 10 μmol/mL is safe and efficient enough to proceed to further clinical trials.     

Enhanced tumor detection in the presence of fatty liver disease: Cell-specific contrast agents

It is assumed that hepatobiliary, cell-specific contrast agents will be adversely affected by the presence of diffuse liver disease. The diagnostic efficacy for tumor detection in the presence of fatty liver disease was experimentally studied at contrast-enhanced magnetic resonance (MR) imaging with manganese-DPDP (N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis[phosphate]) and gadobenate dimeglumine (Gd-BOPTA/dimeg) and compared with conventional and chemical shift imaging. Carcinosarcoma was implanted into the liver of rats, and fatty liver was induced with L-ethionine. Without contrast agents, the tumor-fatty liver contrast-to-noise ratio (C/N) was increased on T1-weighted and decreased on T2-weighted MR images relative to tumor-bearing control rats without fatty liver. Chemical shift imaging (phase-contrast method) increased the tumor—fatty liver C/N from 2.3 ± 1.0 to 6.1 ± 1.7 (P <.001). Mn-DPDP and Gd-BOPTA/dimeg increased the tumor—fatty liver C/N from -5.4 ± 1.6 to -11.0 ± 1.9 and ?9.8 ± 3.4, respectively (P <.001). The hepatobiliary, cell-specific contrast agents were equally effective in both fatty and nonfatty liver and outperformed both chemical shift and conventional MR imaging in detecting liver tumors.     

半乳糖基白蛋白-超顺磁性氧化铁在兔肝脏小肿瘤检出中的应用价值

目的 初步探讨半乳糖基白蛋白-超顺磁性氧化铁(Gal-BSA-SPIO)在肝脏小肿瘤检出中的应用价值.方法 用半乳糖基白蛋白包被小粒径超顺磁性氧化铁(SPIO)制备Gal-BSA-SPIO,测定其粒径大小.建立兔VX2肝癌模型(肿瘤直径＜1.5 cm),用数字表法随机分为Gal-BSA-SPIO和SPIO组,每组10只,每组再分为5和10 μmol Fe/kg组,每组5只.所有实验动物均分别采用SE T2WI、快速自旋回波(FSE)T2WI和梯度回波(GRE)T2WI序列行MR平扫,并按实验分组行增强扫描,分别测量增强前后兔肝脏信噪比(SNR)和肿瘤与肝脏对比噪声比(CNR),并采用方差分析进行比较.扫描完毕后对肝脏及肿瘤组织进行病理检查.结果 Gal-BSA-SPIO平均粒径为34.4 nm,核心粒径为14.8 nm.5 μmol Fe/kg SPIO、5 μmol Fe/kg Gal-BSA-SPIO、10 μmol Fe/kg SPIO和10 μmol Fe/kg Gal-BSA-SPIO 4组增强前后肝脏SNR差值SE序列分别为(1.92±0.42)、(3.75±0.51)、(3.25±0.72)、(4.73±0.34),FSE序列分别为(1.56±0.18)、(3.56±0.64)、(3.33±0.16)、(4.83±0.16),GRE序列分别为(5.55±0.91)、(9.58±0.66)、(9.20±0.29)、(10.63±0.32),不同对比剂及不同序列组间比较差异均有统计学意义(P值均＜0.01).上述4组增强前后肿瘤与肝脏CNR差值SE序列分别为(2.22±0.68)、(5.27±0.22)、(4.25±0.51)、(6.97±0.63),FSE序列分别为(1.73±0.41)、(4.46±0.54)、(3.73±0.49)、(5.39±0.39),GRE序列分别为(5.98±0.71)、(11.79±0.57)、(9.57±0.54)、(14.64±1.35),不同对比剂及不同序列组间比较差异均有统计学意义(P值均＜0.01).Gal-BSA-SPIO主要作用于肝实质细胞,而SPIO主要分布于Kupffer细胞内.结论 Gal-BSA-SPIO具有良好的负向肝脏强化效应,对肝内小肿瘤的检出具有良好的潜在应用价值.     

MR assessment of iodinated contrast-medium-induced nephropathy in rats using ultrasmall particles of iron oxide

The purpose of this study was to determine the diagnostic value of ultrasmall particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations to evaluate experimental nephropathy. This study was conducted in 23 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Eleven rats received selective intra-arterial renal administration of diatrizoate (370 mg I/m1) and were compared to two control groups, including five animals injected with isotonic saline and seven noninjected animals. MR imaging was performed 28 hours after the procedure, including T1- and T2-weighted images before and after intravenous administration of successively 5 μmol Fe/kg and 60 μmol/kg of USPIO. Results were interpreted qualitatively and quantitatively with respect to pathologic data, and differences were studied statistically. The maximal signal intensity decrease was noted in normal kidneys in cortex (?65 ± 4%) and medulla (?84 ± 5%) on T2-weighted images after injection of 60 μmol/kg of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative analysis showed that the highest sensitivity and specificity to diagnose kidney involvement were obtained with T2-weighted MR images (75% and 91%, respectively) when 60 μmol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo evaluation of the severity of experimentally induced iodinated contrast media renal impairment in animals.     

Contrast-enhanced MR imaging of the liver: Comparison between Gd-BOPTA and mangafodipir

The purpose of the study was to evaluate the MR contrast agents gadolinium benzyloxypropionictetro-acetate (Gd-BOPTA) and Mangafodipir for liver enhancement and the lesion-liver contrast on T1W spin-echo (SE) and gradient-recalled-echo (GRE) images. Fifty-one patients (three groups of 17 patients each) with known or suspected liver lesions were evaluated with T1W SE (300/12) and GRE (77-80/2.3-2.5/80°) images before and after intravenous (IV) Gd-BOPTA (0.1 or 0.05 mmol/kg) or Mangafodipir (5 μmol/kg) in phase II to III clinical trials. Quantitative analysis by calculating liver signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and spleen-liver CNR was performed. Liver SNR and spleen-liver CNR were always significantly increased postcontrast. SNR was highest after application of 0.1 mmol/kg Gd-BOPTA (51.3 ± 3.6, P < .05). CNR was highest after Mangafodipir (?22.6 ± 2.7), but this was not significantly different from others (P = .07). Overall, GRE images were superior to SE images for SNR and CNR. Mangafodipir and Gd-BOPTA (0.1 mmol/kg) provide equal liver enhancement and lesion conspicuity postcontrast. By all criteria, contrast-enhanced T1-weighted GRE were comparable to SE images.     

Experimental hepatic dysfunction: Evaluation by MRI with Gd-EOB-DTPA

To investigate the potential of gadolinium (Gd)-ethoxybenzyl (EOB)-diethylenetriamine-pentaacetic acid (DTPA) for evaluating liver function, chemically induced hepatitis animal models were studied. The rats in group 1 underwent intraperitoneal administration of 2.0 ml/kg and those in group 2 underwent intraperitoneal administration of .5 ml/kg of 50% (V/V) carbon tetrachloride (CCl₄) solution. The rats in group 3 served as controls. For rats of each group, the signal intensity of the liver was measured on T1-weighted spin-echo MR images acquired before and until 60 minutes after an intravenous injection of Gd-EOB-DTPA. The remaining rats in each group underwent indocyanine green test, serologic examination, or measurement of prothrombin time. Liver enhancement was compared with results of the other examinations. The degree of liver enhancement with Gd-EOB-DTPA was decreased and the washout of contrast was prolonged in the CCl₄-administered groups. In this animal model, both hepatic dysfunction and liver enhancement were dose-dependent. MRI with Gd-EOB-DTPA has the potential to evaluate hepatic function.     

Double-dose 1.0-M gadobutrol versus standard-dose 0.5-M gadopentetate dimeglumine in revealing small hypervascular hepatocellular carcinomas

The purpose of this study was to compare the diagnostic efficacy of double-dose 1.0-M gadobutrol with that of standard-dose 0.5-M gadopentetate dimeglumine for revealing small hypervascular hepatocellular carcinomas (HCCs). Twenty-three patients with 37 HCCs (mean size: 1.2 cm) that were diagnosed by histology (n = 13) or imaging findings (n = 10) underwent two separate 3D dynamic MRIs with 0.2 mmol/kg of gadobutrol and 0.1 mmol/kg of gadopentetate dimeglumine. Three observers interpreted both MRIs in terms of lesion detection using the alternative-free response receiver operating characteristic method and lesion-to-liver contrast using matched pairs analysis. The two MRIs were also compared quantitatively by measuring the signal-to-noise ratio (SNR) of the liver and lesion as well as the lesion-liver contrast-to-noise ratio (CNR). The SNR of the liver and lesion and lesion-liver CNR with gadobutrol were better than those with gadopentetate dimeglumine (p < 0.01). However, in terms of the diagnostic accuracy (mean Az for gadobutrol: 0.878, and mean Az for gadopentate dimeglumine: 0.873), the sensitivity (92.8%), positive predictive value (92.8% vs. 93.7%) and lesion-liver contrast, the two dynamic MRIs were equivalent. Gadobutrol showed a superior degree of enhancement for hypervascular HCC than did gadopentetate dimeglumine, but the diagnostic capabilities of the two agents for revealing HCCs were equivalent.     

Superparamagnetic iron oxide: Detection of focal liver lesions at high-field-strength MR imaging

AMI-25 was evaluated at 1.5 T as a superparamagnetic iron oxide contrast agent for the liver. Sixteen patients with up to five suspected focal liver lesions were examined with T1-, proton-density—, and T2-weighted spin-echo sequences before and after intravenous administration of AMI-25 (15 μmol/kg iron). The contrast-to-noise ratio (C/N) increased from 1.8 to 3.5 on 600/15 (TR msec/TE msec) images and from 1.7 to 7.9 on 2,500/15 images after AMI-25 administration (P <.01). C/N did not change significantly on 2,500/90 images. Two blinded readers counted the number of lesions visible on unenhanced and contrast-enhanced images, with the 32 sets of images of the 16 patients presented in random order. Both readers identified more lesions on AMI-25–enhanced images, but the difference was not statistically significant (P >.05). Two patients reported minor side effects (flushing, sensation of heat, lower back pain). On the basis of the results obtained in a limited number of patients, the authors conclude that at 1.5 T, AMI-25 does not significantly improve the detection of focal liver lesions on conventional spin-echo images.     

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.     

Effects of ami-25 on liver vessels and tumors on T1-weighted turbo-field-echo images: Implications for tumor characterization

This study was devoted to tumor differentiation in liver MR T1-weighted imaging with superparamagnetic iron oxide (SPIO). Twenty-one patients with 40 liver lesions were studied at 1.5 T. Before and at least 45 minutes after SPIO administration, turbo-field-echo (TFE) T1-weighted, TFE T1 × T2*-weighted (MXT), and fat-suppressed turbo-spin-echo T2-weighted images were acquired. A quantitative analysis was performed blindly. On TFE T1-weighted images, the signal enhancement was ?33% ± 12 for the liver, ?24% ± 2 for adenomas and focal nodular hyperplasia, +60% ± 33 for the hemangiomas; metastases and cyst enhancement were not significant. After SPIO on TFE T1-weighted images, the hemangioma-to-liver signal ratio (149% ± 18) was definitely higher than the mean metastasis-to-liver signal ratio (90% ± 16). This T1-related differentiation ability lacked dramatically on TFE MXT images and, in one case, was reduced on post-SPIO TFE T1-weighted images by a long imaging delay after SPIO administration (2 hours).     

Hepatic tumors: Magnetization transfer MR imaging with gadolinium enhancement

Thirty patients with 15 hepatocellular carcinomas, 10 metastases, four hemangiomas, and one cholangiocarcinoma underwent magnetic resonance imaging at 1.5 T with T1-weighted, T2- weighted spin-echo (SE) images, gradient-echo (GRE) magnetization transfer (MT) images, and gadolinium-enhanced T1-weighted SE and MT- GRE images. The MT effect and lesion-liver contrast-to-noise ratio (C/N) were calculated and visual assessment (qualitative analysis) performed for unenhanced and enhanced MT-GRE images and enhanced Tl-weighted SE images. The C/N values for hepatic adenocarcinomas (seven metastases and one cholangiocarcinoma) and hemangiomas were larger for enhanced MT-GRE images (adenocarcinoma, 8.4 ± 2.3 [P < 0.01); hemangioma, 24 ± 2.1 [P < 0.05]) than for enhanced GRE images (5.0 ± 1.9 and 18 ± 2.7, respectively). These enhancing tumors had the highest scores in the qualitative analysis. Enhanced MT-GRE images showed no advantage for depiction of hepatocellular carcinomas relative to the other images.     

Characterization of a gadolinium-labeled cholesterol derivative as an organ-specific contrast agent for adrenal MR imaging

The purpose of the study was to determine if derivatization of cholesterol with a paramagnetic label could result in an organ-specific contrast agent for magnetic resonance imaging of the adrenal glands. Gadolinium-DO3A-labeled cholesterol was synthesized and the relaxivities in water and blood plasma determined at 0.47 T and 40°C. Organ distribution was measured at 2 (n = 2) and 24 (n = 2) hours after intravenous injection of a 50 μmol/kg dose of Gd-DO3A-cholesterol in rats weighing 220–240 g. T1-weighted spin-echo images were acquired at 2 T before and after injection of 50 μmol/kg Gd-DO3A-cholesterol (n = 2) and Gd-DTPA (diethylenetriaminepentaacetic acid)-albumin (n = 2). More than 99% of the Gd-DO3A-cholesterol was found to be protein bound in bovine serum. High T1 and T2 relaxivities were found in water and plasma. High tissue concentrations of Gd-DO3A-cholesterol were found only in adrenal glands and liver. At 24 hours, adrenal gadolinium concentrations were about 10 times higher than in blood. At 2 hours after injection of Gd-DO3A-cholesterol. enhancement was 162% in adrenal glands and 146% in liver. With Gd-DTPA-albumin, enhancement values were 57% and 56%. respectively.     

Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra- and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5–16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50–120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7–33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg. Received 6 December 1995; Revision received 21 March 1996; Accepted 25 March 1996