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Purpose To investigate the possible role of Zn as a trigger for NSF we were using a previously established preclinical model. The depletion of endogenous Zinc ions (Zn) caused by the administration of gadolinium-based contrast agents (GBCAs) has been suggested as a possible pathomechanism for nephrogenic systemic fibrosis (NSF). Materials and Methods In the Zn supplementation study, rats were injected with Gadodiamide, Omniscan, and Magnevist with or without Zn supplementation. In the Zn depletion study, animals were kept on a Zn-deficient diet or a special control diet and received injections of Omniscan, OptiMARK, Magnevist, Gadovist, and Gd-EDTA. Gd, Zn, and Cu concentrations in tissue were measured and histology of the skin was performed. Results As seen in earlier studies, a difference in Gd concentration in the skin was observed following treatment with the different GBCAs. High Gd concentration in the skin correlated with the occurrence of NSF-like skin lesions. We observed no differences in the occurrence of skin lesions between the Zn supplementation and the Zn-deficient groups compared to their respective control groups. Conclusion We found no significant effect of Zn on the initiation of NSF-like skin lesions. The results further support data from previous studies highlighting the importance of complex stability of the investigated GBCAs. J. Magn. Reson. Imaging 2009;30:374–383. © 2009 Wiley-Liss, Inc.

Various types of intravascular contrast agents, either based on the binding of paramagnetic chelates to carriers such as synthetic polymers or biological macromolecules or on ultrasmall particles of superparamagnetic iron oxides (USPIO), are currently investigated in experimental and clinical studies (1–9). USPIO offer an increased r1/ r2-ratio and a prolonged intravascular retention compared to small particles of iron oxides (SPIO), which were designed as T2*-contrast agents for imaging of the reticuloendothelial system (RES). Therefore, USPIO provide the potential for use as an intravascular contrast agent for T1-weighted MRI (2–6). The purpose of our study was to evaluate imaging properties of different doses of a new ultra-small iron oxide MR contrast agent (SH U 555 C, Schering AG, Germany) for first-pass and equilibrium phase MRA of aortoiliac vessels in elderly male volunteers with risk factors for arterial vascular diseases. MATERIALS AND METHODS

OBJECTIVE:: To evaluate the diagnostic efficacy (accuracy, sensitivity, specificity) of 1.0 M gadobutrol versus 0.5 M gadopentetate for the classification of lesions as either benign or malignant in patients with known or suspected liver lesions. METHODS AND MATERIALS:: A multicenter, phase-III, randomized, interindividually controlled comparison study with blinded reader evaluation was performed to investigate the diagnostic efficacy of a bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentetate at a dose of 0.1 mmol Gd/kg BW.The imaging protocol included a dynamic 3D-evaluation, static conventional, and fat saturated T1-weighted sequences. MR datasets were evaluated by 3 independent radiologists. The standard of reference was defined by an independent truth panel (radiologist or hepatologist).The safety evaluation included adverse events, vital signs, and physical examination. RESULTS:: A total of 497 of 572 patients were eligible for the final efficacy analysis. Noninferiority of gadobutrol-enhanced magnetic resonance imaging (MRI) for the classification of liver lesions was demonstrated on the basis of diagnostic accuracy determined by the on-site investigators (-0.098, 0.021) as well as for the average reader of the blinded evaluation (-0.096, 0.014) (95% confidence interval), compared with the predefined standard of reference. Very similar increases in sensitivity (ranging from approximately 10% to approximately 55%) and specificity (ranging from approximately 1%- approximately 18%) compared with precontrast MRI were also observed for the 2 contrast agent groups, with maximum differences of 4%.Very similar, low rates of adverse events were recorded for each of the 2 groups. No clinically relevant changes in vital signs or the results of the physical examination were observed in any patient. CONCLUSION:: This study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol (0.1 mmol/kg body weight) to 0.5 M gadopentetate (0.1 mmol/kg body weight) in the diagnostic assessment of liver lesions with contrast-enhanced MRI. The known excellent safety profile of gadobutrol was confirmed in this clinical trial and is similar to that of gadopentetate.

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.

Purpose Prospective evaluation of diagnostic accuracy of single field-of-view contrast-enhanced MR Angiography (ceMRA) with 1.0 M gadobutrol compared to intraarterial DSA in body arteries. Materials and methods In an European multicenter study 179 patients underwent ceMRA and DSA. For each indication five prospectively defined vessel segments were evaluated by local investigators onsite and by three site-independent blinded readers (BR) independently. Results The agreement between ceMRA and DSA diagnosis was statistically significant in the onsite (96.6%) and blinded reader (86.6–90.2%) evaluation. Sensitivity, specificity, accuracy, positive (PPV) and negative predictive values (NPV) for detection of relevant stenosis (>50%) were calculated for the right and left internal carotid arteries, and common and external iliac arteries: Sensitivity was 95–98% (onsite) and 76–96% (BR), specificity 94–96% (onsite) and 86–94% (BR), accuracy 96% (onsite) and 87–93% (BR), NPV 98–99% (onsite) and 84–98% (BR), and PPV 79–93% (onsite) and 44–91% (BR), respectively. Conclusion CeMRA of body arteries using 1.0 M gadobutrol provides diagnostic information comparable to intraarterial DSA.