Eovist Injection and Resovist Injection: two new liver-specific contrast agents for MRI.

Eovist Injection (gadolinium-EOB-DTPA) is selectively taken up by hepatocytes, which will increase the signal intensity of normal liver parenchyma on T1-weighted images. This results in improved lesion-to-liver contrast because malignant tumors either do not contain hepatocytes or their functioning is hampered. Following intravenous (i.v.) bolus injection, Eovist Injection is excreted by both the renal and biliary routes. Clinical trials have evaluated the safety and efficacy of Eovist Injection up to a dose of 100 mumol/kg body weight. Resovist Injection (SHU-555A) contains iron-oxide nanoparticles coated with carboxydextran and is administered as an intravenous bolus injection at a fixed-volume dose, dependent on body weight. The uptake of Resovist Injection in the reticuloendothelial (RES) cells results in a decrease of the signal intensity of normal liver parenchyma on both T2- and T1-weighted images. Due to the altered phagocytic distribution and activity, the signal intensity in most metastatic tumors is not affected, resulting in improved lesion-to-liver contrast. Both Resovist Injection and Eovist Injection have exhibited acceptable safety profiles in clinical trials, and have the potential to provide additional information regarding lesion detection, classification, and characterization.

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 ethoxybenzyl-diethylenetriamine-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 micromol/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 degrees) 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 micromol/kg Gd-EOB-DTPA, C/N ratios significantly increased compared to baseline from 90 to 600 s. Postcontrast C/N-values obtained using 50 micromol/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 micromol/kg Gd-EOB-DTPA were slightly superior to 50 micromol/kg Gd-EOB-DTPA. This finding is probably due to a more pronounced extracellular effect of the contrast medium at higher doses.

T1 effects of a bolus-injectable superparamagnetic iron oxide, SH U 555 A: dependence on field strength and plasma concentration--preliminary clinical experience with dynamic T1-weighted MR imaging.

PURPOSE: To investigate the field strength dependency of relaxivity values with SH U 555 A, concentration-dependent T1 effects, and findings at dynamic T1-weighted magnetic resonance (MR) imaging in patients with focal liver lesions. MATERIALS AND METHODS: Longitudinal relaxivity (r1) with SH U 555 A was measured in human plasma (0.02-300.00 MHz), and transverse relaxivity (r2) was measured at 10, 20, and 40 MHz. Second, a dilution series in human plasma was used at 1-T, T1-weighted, spin-echo or fast low-angle shot (FLASH) imaging. In 22 patients with focal liver lesions, imaging with the latter sequence was performed with a dose of SH U 555 A of 10 mumol Fe/kg. RESULTS: The r1 of SH U 555 A decreased with increasing field strength, but was higher at high field strengths than r1 values for gadolinium chelates. Enhancement calculations for different iron concentrations in human plasma demonstrated positive enhancement at concentrations less than 700 mumol Fe/L. Enhancement increased with the degree of T1 weighting and was highest for the FLASH sequence with the shortest TE (+81.4% with 300 mumol Fe/L). Enhancement was positive in the liver for at least 30 seconds and in the spleen for at least 480 seconds. CONCLUSION: Signal intensity changes at dynamic T1-weighted MR imaging after bolus injection of SH U 555 A can be explained by dynamic changes in iron-plasma concentration.

[T1-weighted dynamic MRI with new superparamagnetic iron oxide particles (Resovist): results of a phantom study as well as 25 patients]. / T1-gewichtete dynamische MRT mit neuen superparamagnetischen Eisenoxidpartikeln (Resovist): Ergebnisse einer Studie am Phantom sowie an 25 Patienten.

PURPOSE: Evaluation of the diagnostic usefulness of the T1-effect of Resovist (SPIO) for dynamic MRI of the liver. METHOD: In-vitro measurements of a dilution series with T1-weighted FLASH and SE sequences and investigation of 25 patients with known focal liver lesions with a T2-weighted TSE sequence and a dynamic T1-FLASH sequence. RESULTS: T1-weighted MRI with Resovist in vitro showed a positive enhancement at low concentrations and a negative enhancement at higher concentrations. In-vivo T1-weighted dynamic MRI liver parenchyma demonstrated a positive enhancement 30 s post contrast, followed by a continuous slope of signal intensity and a negative enhancement (> or = 60 s). Spleen, portal venous vessels and haemangiomas showed an early increase in signal intensity followed by a decreasing positive enhancement, but without negative enhancement. During the perfusion phase metastases showed a small but not significant increase in signal intensity. In 80% a positive ring enhancement could be observed around metastases. CONCLUSION: Resovist exhibits a diagnostically useful T1-effect. An evaluation of the perfusion of focal liver lesions during the distribution phase is possible with dynamic T1-weighted MRI. This approach may further improve characterisation of focal liver lesions.

Superparamagnetic iron oxide particles (SH U 555 A): evaluation of efficacy in three doses for hepatic MR imaging.

PURPOSE: To evaluate the efficacy of SH U 555 A in three doses for magnetic resonance (MR) imaging in the liver and to establish the best postinjection time point for liver MR imaging. MATERIALS AND METHODS: Pre- and postcontrast image sets obtained in 169 patients after injection of SH U 555 A (randomly, 4, 8, or 16 mumol of iron per kilogram of body weight). Three blinded readers evaluated the precontrast and 10- and 40-minute postcontrast MR images of 54, 58, and 57 patients, respectively. RESULTS: Statistically significant differences were observed in diagnostic confidence between images obtained with a dose of 4 or 16 mumol Fe/kg (P = .011) and in good or excellent improvement, respectively, in delineation of lesions on 10-minute postcontrast images (P = .001). No apparent differences in the efficacy evaluation were seen between the 10- and 40-minute postcontrast imaging time points. CONCLUSION: There was a dose-dependent postcontrast improvement in evaluated efficacy parameters (diagnostic confidence, visual evaluations) after injection of SH U 555 A. Accumulation phase imaging could begin as early as 10 minutes after administration.

SPIO-enhanced 2D-TOF MR angiography of the portal venous system: results of an intraindividual comparison.

The purpose of this study was to investigate whether MR angiography (MRA) of the portal venous system may be improved by means of superparamagnetic iron oxides (SPIOs) during accumulation phase imaging and to study the underlying contrast mechanisms. MRA of the portal venous system was performed on 48 patients before and after intravenous injection of a new SPIO (Resovist, Schering AG, Berlin, Germany). Resovist, as a predominantly liver parenchymal darkening agent on T2-weighted MR images with uptake into the reticuloendothelial cell system, was administered intravenously by bolus injection of 8 to 12 micromol Fe/kg body weight. Patients were scanned with breath-hold coronal and axial two-dimensional (2D) time of flight (TOF) MRA (TR = 31.0 msec, TE = 9.8 msec, flip angle (FA) = 50 degrees, and 6.9-second acquisition time per section) sequences. Signal intensity values of liver parenchyma, the portal venous system, and background were obtained for quantitative analysis. The clinical relevance of additional plain and contrast-enhanced MRA studies for surgical planning was assessed by independent reading of three readers. Liver signal-to-noise ratio (SNR) significantly decreased following iv injection of Resovist; however, SNR values of the portal veins or hepatic veins did not change significantly. Visibility of the portal venous system improved significantly (tertiary branches visible: pre in 15.2% versus post in 87.0% of patients). Resovist-enhanced 2D-TOF MRA may improve planning of liver resections by better demonstrating the relationship of central liver lesions and vessels on source images. The decrease in liver SNR at a constant vessel SNR after iv injection of Resovist improves MRA of the liver. SPIO-enhanced 2D-TOF MRA scans are superior to plain 2D-TOF MRA studies and may be added for the workup of preoperative patients.

Detection of focal liver lesions: CT of the hepatobiliary system with gadoxetic acid disodium, or Gd-EOB-DTPA.

PURPOSE: To evaluate the efficacy and safety of gadoxetic acid disodium, or Gd-EOB-DTPA, as a tissue-specific hepatobiliary contrast agent at computed tomography (CT) in patients with liver metastases. MATERIALS AND METHODS: Fifteen patients with known liver metastases underwent CT before and at 30, 80, and, in seven cases, 150 minutes after initiation of intravenous infusion of 0.2, 0.35, and 0.5 mmol Gd/kg gadoxetic acid disodium (five patients per dose group). Attenuation in liver tissue and metastases was measured at each time point. Visualization of metastases, bile ducts, and gallbladder was graded subjectively by two investigators aware of the dose administered and the imaging time point. Patients were monitored for adverse events clinically, and numerous laboratory tests were performed over the 24 hours after administration of the contrast material. RESULTS: The net mean increase in liver attenuation with 0.2, 0.35, and 0.5 mmol Gd/kg was 13 HU +/- 4 (standard deviation), 27 HU +/- 6, and 34 HU +/- 8, respectively. Visualization of liver metastases with doses of 0.35 and 0.5 mmol Gd/kg was graded as good or excellent. Visualization of the gallbladder and common bile duct with doses of 0.35 and 0.5 mmol Gd/kg was improved from minimal to excellent in 89% and 57% of patients, respectively, on 80-minute postcontrast scans. No serious adverse events occurred. Four of 15 patients experienced mild or moderate adverse events possibly or probably related to the contrast medium. Levels of aspartate and alanine aminotransferase increased in three patients by 12-26 and 21-48 U/L, respectively, from normal or moderately elevated baseline levels. These changes may be related to the contrast medium or to the metastases. CONCLUSION: Patient tolerance of gadoxetic acid disodium was acceptable, and liver enhancement and visualization of liver lesions and the biliary system was improved at CT.

[Dynamic and static MRI using superparamagnetic MRI contrast medium Resovist for visualizing primary and secondary liver tumors]. / Dynamische und statische MRT mit dem superparamagnetischen MRT-Kontrastmittel Resovist zur Darstellung von primären und sekundären Lebertumoren.

PURPOSE: To analyse characteristics of benign and malignant liver tumours in dynamic and static MR imaging with the superparamagnetic MR contrast medium Resovist. MATERIAL AND METHODS: All 30 patients were examined on a 1.5 Tesla MR unit (Magnetom 63 SP, Siemens AG, Erlangen, Germany) using proton density (PD) weighted (w), T2-weighted-spin-echo, a T1-weighted SE, and a T1-weighted FLASH-2 D gradient echo (GRE) sequence before, during and after the application of Resovist. Dynamic imaging was performed using a T2-weighted GRE-sequence (TurboFLASH; TR/TE = 11/30; flip angle = 10 degrees; Tl = 600 ms). Histopathology revealed benign liver lesions in 8 patients and malignant lesions in 22 patients. RESULTS: Dynamic T2-weighted sequence revealed an early loss of signal intensity in normal liver parenchyma (percentage signal intensity loss (PSIL) = 40.0 +/- 12.2% by 4 mumol Fe/kg, 47.2 +/- 18.8% by 8 mumol Fe/kg and 62.7 +/- 13.0% by 16 mumol Fe/kg), in the spleen, as well as in FNH (PSIL = 49.5 +/- 7.3% by 8 mumol Fe/kg), and regenerating nodules in the first minute after application of Resovist. In two of 4 cases with HCC a short drop in signal intensity was immediately observed after the application, whereas signal intensity remained unchanged in all other malignant liver tumours. Enhanced PDw and T2-weighted SE-sequences revealed an improved detection and delineation of malignant liver lesions versus plain MR imaging. 17 liver lesions of a size lower 10 mm were additionally detected in postcontrast T2-weighted SE-sequences in 4 patients. CONCLUSION: Dynamic and static versus plain MR imaging of primary and secondary liver lesions is markedly improved by the superparamagnetic contrast material Resovist, especially in case of intravenous bolus application of this liver-specific contrast medium.

Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence.

PURPOSE: To investigate the efficacy of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in the detection of focal liver lesions with respect to dose, side effects, and pulse sequence. MATERIALS AND METHODS: A randomized double-blinded trial was performed in 33 patients with focal solid liver lesions. A bolus of Gd-EOB-DTPA, a liver-specific contrast agent, was intravenously administered at three different doses (12.5, 25, and 50 mumol per kilogram of body weight). Magnetic resonance imaging with different T1-weighted techniques was performed 20 and 45 minutes after administration of Gd-EOB-DTPA. Changes in liver signal intensity, lesion-liver contrast-to-noise ration (C/N), detectable liver lesions, side effects, and adverse events were evaluated. RESULTS: Gd-EOB-DTPA significantly (P < .05) increased liver signal intensity and lesion-liver C/N within the dose range tested. Lesion detection was improved 20 and 45 minutes after administration of Gd-EOB-DTPA. A dose of 12.5 mumol was sufficient for the detection of focal liver lesions, and the breath-hold, T1-weighted, fast low-angle shot pulse sequence was the most useful. No significant changes in vital signs, clinical laboratory test results, and urinalysis were observed. CONCLUSION: Gd-EOB-DTPA is an efficient, diagnostically useful, and safe contrast agent.

[New MR contrast media in liver diagnosis. Initial clinical results with hepatobiliary Eovist (gadolinium-EOB-DTPA) and RES-specific Resovist (SH U 555 A)]. / Neue MR-Kontrastmittel in der Leberdiagnostik. Erste klinische Ergebnisse mit hepatobilliärem Eovist (Gadolinium-EOB-DTPA) und RES-spezifischem Resovist (SH U 555 A).

The purpose of this work is to describe our initial clinical experience (in 66 patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We focus our report on safety aspects, dose finding, and optimization and technical parameters. Both contrast agents were well tolerated and improved the detectability of focal liver lesions. With Resovist, postcontrast MRI may be started as early as 10 min following injection. The dose of 8 mumol Fe/kg bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels. Since Eovist can also be administered as a bolus, dynamic enhancement patterns may be studied for tumor characterization as well. Breath-hold T1-weighted FLASH images were superior to other T1-weighted techniques with and without fat saturation.

Bilateral primary synchronous renal cell carcinoma.

We report a case of bilateral primary "synchronous" renal cell carcinoma (RCC) with different differentiation rates. Computed tomography (CT), ultrasonography (US), angiography, and fine needle aspiration biopsy (FNAB) were performed followed by right radical and left partial nephrectomy. Findings on ultrasonography were non-specific, CT scan showed bilateral solid renal mass. On angiography of the right renal artery no tumoral vessels were seen and FNAB yielded a false negative result on the left side. Histological examination revealed a cystic renal cell carcinoma on the right and a multinodular renal cell carcinoma on the left side. We could not find similar report in the current literature.

Crohn's disease and sclerosing cholangitis: CT and PTC diagnosis, with MR findings.

Computed tomography (CT), percutaneous transhepatic cholangiography (PTC) and magnetic resonance imaging (MRI) findings in a case of sclerosing cholangitis associated with Crohn's disease of the colon and terminal ileum are described. CT gives additional information on dilatation of peripheral bile ducts and confirms findings of PTC, i.e. a decreased arborization of the biliary tree, a nodular appearance of the common bile duct and multifocal bile duct strictures. CT findings could be recognized on MRI which provided no additional information.

Is it a haemangioma?

A retrospective study of 92 cases of proven haemangiomas is presented. In this study, we evaluated the degree of confidence of the radiologist in differentiating haemangioma by ultrasound (US), computed tomography (CT), angiography (AR), and magnetic resonance imaging (MRI) in an incidental and an oncologic (high risk) population. The diagnosis of haemangioma was confirmed by surgery, by fine needle aspiration biopsy (FNAB) and by long follow-up. Maximum lesions were diagnosed with high confidence by MRI (88-93%) and by angiography (85-91%) in both incidental and oncologic group. 44% of the lesions were confidently diagnosed in incidental group as compared to the 11% of the lesions in oncologic group by ultrasound. Similarly, lesions were diagnosed with maximum confidence in 76% in incidental group as compared to 48% in oncologic group by dynamic contrast bolus CT. Confidence was also evaluated according to the size of the lesions but due to the low number of lesions in < 1.5 cm category, the difference in the confidence levels was not apparent. We conclude that in high risk group, MRI, if available, should be directly performed after US. In the incidental finding group, if the lesion has typical features, US follow-up every 6 months is sufficient.

Some salient features of 'Kitabul-Hashaish' with special reference to the manuscript preserved in Khuda Baksh O.P. Library, Patna.

The contributions of Dioscorides in the field of materia medica and pharmacology are unparalleled in the history of medicine. This great botanist of the 1st century A.D. made personal observations of the specific properties of drugs and presented them through illustrations for the first time. Almost all the physician authors of Unani system of medicine from Galen to Azam Khan have quoted Dioscorides. Kitabul-Hashaish was rendered into English and arabic and published repeatedly in the West. The book has great value and is quoted widely due to its authenticity. This unique work needs to be edited critically and afterwards translated into Urdu and other languages for the benefit of the present day students and scholars.

Unusual cystic liver lesions: a pictorial essay.

Cystic liver lesions are being increasingly detected by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). These lesions produce a wide spectrum of radiological features. Unfortunately their appearance is not always specific and they may resemble and be mistaken for other lesions. Cystic lesions can be classified into congenital, inflammatory, neoplastic and miscellaneous groups. In this pictorial essay a number of unusual cystic lesions are illustrated with a brief analysis of morphological features of the individual lesion and a diagnostic approach for cystic liver lesions is suggested.

Mucinous cystadenocarcinoma of the pancreas with liver metastases. An unusual presentation of a rare tumor.

We present a case of mucinous cystadenocarcinoma of the pancreas with liver metastases. Initially, the patient presented as pancreatitis and pseudocyst which was marsupialised into the stomach in 1983. Eight years later, a tumor with liver metastases was detected. The liver metastases mimicked multiple abscesses. Over a period of forty-four days, CT features changed considerably and there was explosive enlargement of the lesions in the postoperative period. The reason for this dramatic increase in size was the anaplastic component of the tumor. To our knowledge, no such case has been reported in literature.