Liver-specific Contrast Media Research Articles

Characterization of Focal Liver Lesions using CEUS and MRI with Liver-Specific Contrast Media: Experience of a Single Radiologic Center.

The purpose of this study was to compare contrast-enhanced ultrasound (CEUS), magnetic resonance imaging (MRI) using liver-specific contrast agent and a combination of both for the characterization of focal liver lesions (FLL). 83 patients with both benign and malignant liver lesions were examined using CEUS and MRI after the intravenous administration of liver-specific contrast media. All patients had inconclusive results from prior imaging examinations. Histopathological specimens could be obtained in 53patients. Ultrasound was performed using a multi-frequency curved probe (1 - 6 MHz) after the injection of 1 - 2.4 ml ultrasound contrast media. The sensitivity, specificity, positive predictive value and negative predictive value of CEUS, MRI and a combination of both (CEUS + MRI) were compared. The sensitivity, specificity, positive and negative predictive values regarding lesion classification were 90.9 %, 70.6 %, 92.3 % and 66.6 %, respectively, for CEUS; 90.9 %, 82.4 %, 95.2 % and 70.0 %, respectively, for MRI; and 96.9 %, 70.6 %, 92.7 % and 85.7 % respectively, for CEUS + MRI. There were no statistically significant differences. 6 malignant lesions were missed using CEUS or MRI alone (false negatives). The use of both modalities combined reduced the false-negative results to 2. CEUS and MRI with liver-specific contrast media are very reliable and of equal informative value in the characterization of focal liver lesions. The number of false-negative results can be decreased using a combination of the two methods.

Abdominal radiology in oncology: The new trends in computed tomography and magnetic resonance imaging

Paper gives a review of recent technical innovations in computed tomography (CT) and magnetic resonance imaging (MRI) that could be applied in abdominal oncology. Perfusion and dualenergy CT gives new opportunities for tissue characterization. Interactive reconstruction algorythms decrease radiation exposure to patients. Abdominal MRI has some important advantages over CT in detection and staging of abdominal malignancies. Nowadays standard MR protocols include DWI and dynamic 3D sequences with extracellular or liver-specific contrast media. Latest developments in MRI technology could expand its diag- nostic value in abdominal oncology even further.

Irreversible electroporation of hepatocellular carcinoma: preliminary report on the diagnostic accuracy of magnetic resonance, computer tomography, and contrast-enhanced ultrasound in evaluation of the ablated area.

Irreversible electroporation (IRE) is a new ablation modality. Our purpose was to describe the effectiveness and the safety of the treatment and to evaluate the magnetic resonance imaging (MRI), computed tomography (CT) and contrast-enhanced ultrasound (CEUS) diagnostic accuracy in HCC patients treated with IRE at 1-, 3-, and 6-month follow-up. In an 18-month period, we treated 24 HCC lesions in 20 patients unfit for surgery. MRI, CT and CEUS were performed before and one, 3 and 6 month after IRE. We employed the liver-specific contrast medium Primovist (gadolinium ethoxybenzyl dimeglumine) in MRI. After IRE the lesions were classified as responders or non-responders to the treatment according to the mRECIST and the complications were recorded. We evaluated the size, shape, signal intensity (T1-W, T2-W, and DWI) in MRI, dynamic contrast enhancement pattern for CEUS, CT and MRI and signal behavior during the liver-specific phase for MRI. According to mRECIST, at 1 month MRI and CEUS showed a complete response (CR) in 91.7% of cases (22/24) tumors, while there was partial response (PR) in the remaining 2/24 (8.3%) treated nodules; in CT study all ablated zone appeared as necrotic (CR 100%). The residual viable tumor in MRI and in CEUS study had similar diameter (10 mm). No new HCC were identified from MRI, CT or CEUS. At 3 months MRI and CEUS showed the same results seen after 1 month from the treatment. Twenty-two necrotic lesions, and 2 residual tumors were found (CR = 91.7% and PD = 8.3%). In MRI study the two cases of residual tumor tissue had a diameter of 11 and 12 mm each. At CEUS the diameter of residual HCC was similar to the diameter at 1 month. CT showed 23 necrotic areas and one residual viable tissue in the treated zone, with a diameter of 10 mm (CR = 95.3% and PD = 4.7%). No new foci of HCC were identified from all imaging studies. At 6 months MRI, CEUS, and CT showed 22 necrotic lesions and 2 residual tumors in ablated zone (CR = 91.7% and PD = 8.3%). At MRI the diameters of the two residual viable HCCs were 12 and 14 mm, at CEUS the diameters were 11 and 12 mm, while at CT the diameters were 10 and 10 mm. No statistical difference was evaluated between CR, PR, PD percentage values for MRI, CT and CEUS (p value > 0.05 at Chi-square test). No major vascular complication was recorded after IRE. Six out of 20 patients (30%) showed a transient hepatic intensity difference (THID) area within the normal liver parenchyma adjacent to the treated lesions. Two of the 20 patients (10%) showed an absent concentration of liver-specific contrast medium around the ablation zone. Two patients developed complications, consisting in a peripheral arteriovenous shunt and a segmental dilation of the intrahepatic biliary ducts. We found no statistically significant difference in morphology, size (variation in the largest diameter), signal intensity in T1-weighted images, in T2-weighted images, in DWI and in the related map of the apparent diffusion coefficient (ADC), presence or absence of contrast enhanced during the arterial, portal, and late phase in MRI, CT, and CEUS, and signal characteristic during the liver-specific phase in MRI of the ablation zone at 1, 3, and 6 months. IRE is a feasible, safe and efficient modality in the treatment of patients with non-resectable HCC. We had no major complication, even when the ablated lesion was adjacent to major branches of the portal vein. All images techniques showed similar accuracy during the follow-up at 1, 3, and 6 months in the assessment ablated zone.

MR imaging features for improved diagnosis of hepatocellular carcinoma in the non-cirrhotic liver: Multi-center evaluation

PurposeTo determine MR-imaging features for the differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver. Material and Methods107 consecutive patients without liver cirrhosis (46 male; 45±14 years) who underwent liver resection due to suspicion of HCC were included in this multi-center study. The following imaging features were assessed: lesion diameter and demarcation, satellite-lesions, central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal-intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center versus periphery). In addition, contrast-media (CM) uptake in the liver specific phase was analyzed in a sub-group of 42 patients. ResultsSignificant differences between HCC (n=55) and benign lesions (n=52) were shown for native T1-, T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all, P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81), T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91% and 75% respectively for two out-of four independent predictors, whereas specificity reached 98% for all four predictors. Sub-analysis, showed significant differences in liver specific CM uptake between HCC (n=18) and benign lesions (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7) as additional independent feature for diagnosis of HCC. ConclusionIndependent MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity, lack of central tumor-enhancement, presence of satellite-lesions and lack of liver specific CM-uptake. These features may have the potential to improve the diagnosis of HCC in the non-cirrhotic liver.

Liver-specific magnetic resonance contrast medium in the evaluation of chronic liver disease.

ABSTRACTThe hepatobiliary-specific contrast medium (gadoxetic acid – Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis.

Percutaneous ablation therapy of hepatocellular carcinoma with irreversible electroporation: MRI findings.

Irreversible electroporation is a new ablation modality. Our purpose was to describe the MRI findings after irreversible electroporation treatment of hepatocellular carcinoma (HCC). In an 18-month period, we treated 24 HCC lesions in 20 patients who were not candidates for surgery. MRI was performed before and 1 month after irreversible electroporation. We used the liver-specific contrast medium gadoxetic acid. We evaluated the size, shape, signal intensity (T1-weighted, T2-weighted, and diffusion-weighted imaging), dynamic contrast enhancement pattern, and signal behavior during the liver-specific phase. Changes in the perilesional parenchyma, perfusion abnormalities, and complications were also recorded. According to the modified Response Evaluation Criteria in Solid Tumors system, 22 of 24 lesions had a complete response, and two lesions showed a partial response and were retreated. The lesions showed a mean size increase of 10%, with a round or oval shape. On the T1-weighted images, we observed a hyperintense core and a hypointense rim. On the T2-weighted sequences, the signal was heterogeneously hypointense. On diffusion-weighted images, 83% of lesions showed restricted diffusion, with b values of 0-800 s/mm(2), whereas in 17% of the lesions, the signal was not clearly discernible for different b values. The apparent diffusion coefficient values did not show statistically significant differences between the baseline (800-1020 × 10(-3) mm(2)/s) and the reassessment after 1 month (900-1100 × 10(-3) mm(2)/s). The necrotic area did not show a signal increase after contrast material injection. Perfusion abnormalities, such as areas of transient hepatic intensity difference, were present in the tissue adjacent to six treated lesions. In two patients, a reduced or absent concentration of the contrast medium was observed during the liver-specific phase around the ablation zone. One patient had an arteriovenous shunt and another had biliary duct dilatation. MRI detects characteristic morphologic and functional changes after irreversible electroporation treatment.

Description of focal liver lesions with Gd-EOB-DTPA enhanced MRI.

Imaging procedures play a fundamental role in the therapeutic management of focal liver lesions. The goals of imaging are to detect and correctly characterize focal liver lesions. This review highlights the performances of newer, liver-specific, contrast media in the diagnosis of focal liver lesions, particularly Gd-EOB-DTPA (Primovist), the most frequently used liver specific contrast media.It has been shown, in different papers, that Gd-EOB-DTPA has better performances compared to either triphasic contrast enhanced computed tomography or dynamic MRI in both detection and characterization of hepatocellular carcinoma on the cirrhotic liver. Therefore liver MRI with Primovist is considered, in many centers, the “state-of-the-art” imaging examination of the liver before surgery or liver transplantation.Gd-EOB-DTPA is also useful in the differential diagnosis of benign hypervascular focal liver lesions such as adenomas or focal nodular hyperplasias.

Continuous dynamic registration of microvascularization of liver tumors with contrast-enhanced ultrasound.

Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS) measured continuously from the arterial phase to the late phase (3 minutes). Material and Methods. We present a retrospective analysis of 20 patients with malignant (n = 13) or benign (n = 7) liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5 T MRI (liver specific contrast medium) or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5 MHz) and a bolus injection of 2.4 mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak), RBV (regional blood volume), RBF (regional blood flow), and Peak. Results. Statistics revealed a significant difference (P < 0.05) between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP (P = 0.07). Receiver operating curves (ROC) were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors.

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

PurposeThe purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3T. Materials and methods93 patients with normal (n=54) and cirrhotic liver (n=39; Child–Pugh class A, n=18; B, n=16; C, n=5) underwent contrast-enhanced MRI with liver specific contrast media at 3T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. ResultsMean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B+C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p=0.501) and significantly reduced in case of C cirrhosis (p=0.043) during HBP. ConclusionRE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B+C cirrhosis.

Magnetic Resonance–Guided Freehand Radiofrequency Ablation of Malignant Liver Lesions

The aims of this study were to develop magnetic resonance (MR)-guided freehand radiofrequency ablation (RFA) using a near-real-time interactive MR platform in an open 1.0-T MR scanner and to determine the feasibility and safety of this new approach in the clinical setting. The study was performed using an open 1.0-T MR system and a low-pass filter to prevent interaction between the RFA generator and the scanner. Artifact size of the radiofrequency needle was measured in 2 perpendicular views (transversal [tra] and coronal [cor]) in vitro and in the tra orientation in vivo for diagnostic (T1 high resolution isotropic volume excitation [THRIVE]/T2 turbo spin-echo [TSE]) and near-real-time (T1 fast-field-echo [FFE]) imaging. A liver-specific contrast medium (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) was administered 20 minutes before the intervention to enhance lesion visibility. Visibility was rated and compared for both interventional and diagnostic imaging sequences using a 10-point grading scale. Intervention time and complications were recorded. The mean diameter of needle artifact size for interventional T1 FFE was 17.4 ± 0.7 mm (tra) and 17.1 ± 1.1 mm (cor) in vitro and 15.2 ± 1.5 mm (tra) in vivo. Artifact size for diagnostic imaging was 12.5 ± 1.8 mm (tra) and 11.2 ± 1.4 mm (cor) in vitro and 10.5 ± 1.7 mm in vivo using THRIVE and 8.1 ± 2.4 mm (tra) and 10.8 ± 1.8 mm (cor) in vitro and 9.7 ± 2.0 mm (tra) in vivo using T2 TSE. A total of 57 patients with liver malignancies (mean tumor size, 17 ± 7 mm) underwent freehand MR-guided RFA. In all patients, the ablative procedure was technically successful. Lesion visibility of the diagnostic T2 TSE sequence (4 ± 2) was significantly decreased compared with both the diagnostic (THRIVE, 7 ± 2) and interventional (T1 FFE, 8 ± 1) T1-weighted sequences. Mean time to position the applicator was 7.5 ± 2 minutes. Procedure times ranged from 30 to 60 minutes. The mean in-room time was 57 ± 22 minutes. No major complications were recorded. Magnetic resonance-guided freehand RFA using a near-real-time interactive MR platform in an open 1.0-T MR scanner is feasible, safe, and applicable in clinical routine. The administration of a hepatocyte-specific contrast agent enhances lesion visualization and therefore improves targeting. Without the need for additional sophisticated devices, this new approach simplifies and shortens the RFA procedure compared with previously published methods.

Liver specific magnetic resonance imaging contrast medium for evaluation of focal liver lesions – Initial experience at a service hospital

BackgroundContrast enhanced MRI is today considered the investigation modality of choice in detection and characterization of focal liver lesions. The conventional MRI contrast media like Gadolinium (Gd) chelates undergo elimination through the urinary pathway and are not selectively concentrated or metabolized in the liver. Gadobenate dimeglumine (Chemical name: Gadolinium-BOPTA) is a promising newer liver specific MRI contrast medium having additional properties of selective uptake and biliary excretion by hepatocytes. Our study was designed as a pilot study to evaluate the utility of Gd-BOPTA in detection and characterization of focal liver lesions. MethodsFifty-three consecutive patients with focal liver lesions (excluding only simple hepatic cysts) detected on ultrasonography and CT abdomen, were prospectively subjected to standardized MRI protocol for the liver, using Gd-BOPTA as the intravenous contrast medium. An additional T1W axial scan of the liver was incorporated in the study protocol, at a delay of 2 h post-contrast, in all patients. ResultsIn the study population, the combination of USG and contrast enhanced CT abdomen findings were adequate to reach a definitive diagnosis in 70% of the patients. The liver specificity of Gd-BOPTA contributed to improved lesional characterization in 9/50 patients (18%) on the delayed phase images. ConclusionThe study revealed that the liver specific properties of Gd-BOPTA can be used to obtain additional information to improve characterization of focal hepatic lesions, when delayed phase scans are included in the study protocol.

Is hepatotropic contrast enhanced MR a more effective method in differential diagnosis of hemangioma than multi-phase CT and unenhanced MR?

BackgroundCavernous hemangiomas are the most frequent neoplasms of the liver and in routine clinical practice they often need to be differentiated from malignant tumors and other benign focal lesions. The purpose of this study is to evaluate whether diagnostic accuracy of magnetic resonance imaging (MRI) of hepatic hemangiomas, showing atypical pattern on US, improves with the use of Gd-BOPTA in comparison with contrast-enhanced multi-phase computed tomography (CT).Methods178 consecutive patients with ambiguous hepatic masses showing atypical hyperechoic pattern on grey-scale US, underwent unenhanced and contrast-enhanced multi-phase multi-detector CT and MR (1.5T) with the use of liver-specific contrast medium gadobenate dimeglumine (Gd-BOPTA). After intravenous contrast administration arterial (HAP), venous-portal (PVP), equilibrium phases (EP) both in CT and MR and additionally hepatobiliary phase (HBP) in MR were obtained. 398 lesions have been detected including 99 hemangiomas and 299 other lesions.ResultsIn non-enhanced MDCT examination detection of hemangiomas was characterized by sensitivity of 76%, specificity of 90%, PPV of 71%, NPV of 92% and accuracy of 86%.Non-enhanced MR examination showed sensitivity of 98%, specificity of 99%, PPV of 99%, NPV of 99% and accuracy of 99%.After intravenous administration of contrast medium in MR the mentioned above parameters did not increase significantly.ConclusionGd-BOPTA-enhanced MR in comparison with unenhanced MRI does not improve diagnostic accuracy in discriminating hemangiomas that show non-specific appearance in ultrasound examination. Unenhanced MR as a method of choice should directly follow US in course of diagnostic algorithm in differentiation of hemangiomas from other liver tumors.

A case of Budd-Chiari syndrome: Gd-EOB-DTPA-enhanced MR findings

Budd-Chiari syndrome (BCS) is a rare disorder caused by the obstruction of hepatic venous outflow, leading to sinusoidal congestion, ischemic injury to liver cells and portal hypertension. Long-term survival largely depends on whether hepatocellular carcinoma occurs. A recently available liver-specific contrast medium, gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), reportedly has high diagnostic capability for detection of malignant liver tumors. However, there has been no report of the sue of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for BCS. We present a case of chronic BCS who underwent both gadopentetate dimeglumine (Gd-DTPA) and Gd-EOB-DTPA-enhanced MRI. Hepatic congestion and edema were seen as slightly hypointense areas on Gd-EOB-DTPA-enhanced hepatobiliary-phase images, although these areas were observed as slightly hyperintense on previously obtained Gd-DTPA-enhanced delayed-phase image. Reduced uptake of Gd-EOB-DTPA by hepatocytes in the region of congestion or edema may account for this difference, which should be recognized in image interpretations.

New real-time image fusion technique for characterization of tumor vascularisation and tumor perfusion of liver tumors with contrast-enhanced ultrasound, spiral CT or MRI: First results

Evaluation and characterization of the vascularisation and perfusion of liver tumors by means of image fusion of dynamic contrast-enhanced ultrasound (CEUS), multidetector-CT (MD-CT) or magnetic resonance imaging (MRI) with the ultrasound navigation technique. For interventional planning a real-time image fusion involving CEUS (LOGIQ E9, GE) was performed in 20 patients (12 men, 8 women, age 43-69 years, median 54) with histologically confirmed malignant liver tumors (9 x hepatocellular carcinoma (HCC), 5 x metastases, 2 x hemangiomas, 1 x cholangiocellular carcinoma (CCC), 1 x lymphoma, 1 x neuroendocrine tumor, 1 x focal nodular hypoplasia (FNH)). In 17 patients the real-time CEUS was fused with contrast-enhanced MD-CT and in three patients with contrast-enhanced MRI (Gd-DTPA and liver-specific contrast medium Resovist. All of the ultrasound examinations were performed by an experienced examiner with a multi-frequency probe (2-5 MHz, LOGIQ E9, GE); dynamic image sequences up to 3 minutes in true agent detection mode of contrast harmonic imaging (CHI) were documented. An evaluation of the tumor was performed by the characterization of the dynamics of the contrast medium and microperfusion with CEUS, fused with MD-CT or MRI. In 18/20 cases there was an accurate agreement with respect to the segmental localization of the tumor lesion. In 2/20 cases the localization was comparable with the image fusion of CEUS and reference imaging (a total of at least 65 lesions: 3 x 1 lesion, 5 x 2 lesions, 8 x 3 lesions, 2 x 5 lesions, 1 x 8 lesions, 1 x at least 10 lesions (multifocal)). With image fusion a certain characterization was attained in 17/20 cases. In 3/20 cases (lymphoma after liver transplantation, multifocal CCC, metastases of a neuroendocrine tumor) the diagnosis was at first doubtful and had to be confirmed histologically. In patients with HCC an evaluation of the tumor perfusion was feasible in all 9 cases (8/9 after local trans-arterial chemoembolization (TACE), 1/9 after radio frequency ablation (RFA)). A tendency toward the identification of more lesions with image fusion of CEUS and CT than with contrast-enhanced CT alone could be recognized (p=0.059). Applying a new real-time fusion technique of MD-CT or MRI with CEUS new possibilities for the evaluation, intervention and monitoring of the therapy of liver lesions were made possible, since the method also comprised the dynamic microperfusion.

Contrast agents for hepatic MRI

Liver specific contrast media (LSCM) can be subdivided according to different modalities of hepatic distribution: exclusive distribution to the hepatocellular compartment can be obtained using CM which accumulate within the hepatocytes after slow infusion; other CM demonstrate combined perfusion and hepatocyte-selective properties, with an initial distribution to the vascular-interstitial compartment (in an analogous manner to that of the conventional extracellular CM), thereafter, a fraction of the injected dose is taken up into the hepatocytes causing an increase in the signal intensity of the hepatic tissue. The use of the superparamagnetic effect of iron oxide particles is based on distribution in the reticuloendothelial system (RES), usually well represented in the normal parenchyma as well as in benign hepatocellular lesions, and absent in most malignant lesions. It is necessary to have an in-depth knowledge of either the biological and histological characteristics of focal liver lesions (FLL) or the enhancement mechanism of LSCM to gain significant accuracy in the differential diagnosis of FLL. Dynamic contrast-enhanced MRI is an important tool in the identification and characterization of FLL. With LSCM it is possible to differentiate benign from malignant lesions and hepatocellular lesions from non hepatocellular lesions with high accuracy. To understand the contrast behaviour after injection of LSCM it is necessary to correlate the contrast enhancement with both the biological and histological findings of FLL.

Imaging Liver Metastases with a New Oral Manganese-Based Contrast Agent

The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. The study included 10 consecutive patients with known liver metastases. Patients underwent abdominal MRI as a supplement to routine diagnostics. Patients fasted for at least 10 hours before ingesting CMC-001 (1.6 g manganese chloride tetrahydrate, 1 g alanine, and 1,600 IU vitamin D3 were dissolved in water). MRI took place before and 2 hours after drinking CMC-001. The 1.5-T MRI protocol included two-dimensional T1w sequences to visualize metastases. T2w and diffusion weighted imaging (DWI) sequences were used to identify cysts and blood vessels correspondingly. The intake of CMC-001 caused an increase in the signal intensity of the "healthy" liver tissue, making the internal structure of the liver significantly better visualized. Compared with our routine examinations, MRI showed more metastases in four patients and allowed determining a more precise outline of metastases. CMC-001 improves imaging of liver metastases in comparison with computed tomography and with MRI without CMC-001.

Labelling of cultured macrophages with novel magnetic nanoparticles

Magnetic resonance (MR) imaging is capable of demonstrating human anatomy and pathological conditions. Iron oxide magnetic nanoparticles (MNPs) have been used in MR imaging as liver-specific contrast medium, cellular and molecular imaging probes. Because few studies focused on the MNPs other than iron oxides, we developed FeNi alloy MNPs coated with polyethylenimine (PEI). In this study, we demonstrated PEI-coated FeNi MNPs are able to label the cells, which could be detected in MR imaging. For labelling purpose, MNPs were incubated with mouse macrophage cell line (Raw 264.7) for 24 h and these PEI-labelled FeNi alloy MNPs can be uptaken by macrophages efficiently compared with Ferucarbotran, a commercialized superparamagnetic iron oxide (SPIO) under flow cytometry measurement. Besides, these cells labelled with MNPs could be imaged in MR with the identical potency as Ferucarbotran. Further investigation of the cells using Prussian blue staining revealed that FeNi alloy MNPs inside the cells is not oxidized. This phenomenon alleviated the consideration of potential risk of nickel toxicity. We conclude that PEI-coated FeNi MNPs could be candidate for MR contrast medium.

New RES-Specific Contrast Agents for CT

Several liver-specific contrast media have been developed for improved detection and characterization of liver tumors. Most of these agents were designed for magnetic resonance imaging (MRI) (1–5). However, up to now, computed tomography (CT) remains the primary imaging modality for most patients with suspected liver disease (6,7). Therefore, development of organ-specific contrast media for CT, that are both safe and efficacious, is of great clinical importance. One approach of liver targeting has been the encapsulation of a water-soluble iodinated contrast agent inside liposomes. Like other particulate agents, liposomal contrast media are taken up by the reticuloendothelial system (RES), which should give them an advantage over conventional extracellular contrast agents for liver imaging. Several studies have described liposomal encapsulation with several iodinated contrast agents, such as iopromide, iopromidol, iotrolan, diatrizoate, and others (8–13). Although some of these agents have been shown to be effective contrast media for liver imaging, results have been not entirely satisfactory, mostly because of safety reasons (high rates of adverse events). Therefore, further research is needed to develop a safe and efficacious liposomal contrast agent for CT imaging. In this study, we explored the enhancement efficacy of two new liposomal formulations, BR 23 and BR 24 (Bracco Research, Geneva, Switzerland), which contain iomeprol, a low viscous nonionic dimer, for CT imaging of liver and spleen in primates. These preparations contain both encapsulated and unencapsulated iomeprol. An additional aim of this study was to compare these two new agents to Imeron 300, which is already in clinical use.

Relationship between contrast enhancement and diagnostic accuracy with the liver-specific CT contrast medium FP 736-04 in an experimental model of liver metastases.

The authors sought to establish the optimal level of liver enhancement at computed tomography (CT) with a hepatocyte-specific contrast medium in an experimental model of liver metastases. Anesthetized nude rats (n = 18) injected intraportally with cells from human colonic adenocarcinoma and Sprague-Dawley rats (n = 11) without metastases were used. A fractional intravenous infusion of contrast material was given in escalating doses up to a total of 4.0 mL per kilogram of body weight. Mean attenuation of the liver was calculated for each accumulated dose, and the overall detection rate was determined on a lesion-by-lesion basis. Sensitivity, specificity, and positive and negative predictive values were also established for each dose. Liver metastases were diagnosed with increasing reliability for enhancement values of up to 30.0 HU +/- 5.2 (mean +/- standard deviation), which corresponded to a dose of 0.5 mL/kg. In this model, optimal reliability in the diagnosis of liver metastases with CT was achieved at an enhancement value of approximately 30 HU.

A New Liposomal Contrast Medium for CT of the Liver

A new type of liposomal liver-specific contrast medium was studied in an experimental tumour model. Rabbits were inoculated with VX2-carcinoma directly into the liver at laparotomy. CT studies were carried out 14 days after inoculation. The liver-specific contrast medium consisted of a suspension of liposomes in a 100 mg I/ml iodixanol solution, with equal amounts of encapsulated and nonencapsulated iodixanol. It was administered at a dose of 200 mg I/kg. The contrast of normal liver tissue to tumorous tissue was significantly increased by contrast medium administration, the increase being largest 10 min after injection.