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MAGNETIC RESONANCE IMAGING


FigUre 2. Markedly improved contrast enhancement, lesion delineation and depiction of internal lesion morphology is achieved on MRI enhanced with MultiHance (A) than on MRI enhanced with Gadovist (B) when both contrast agents are administered under identical conditions at an equivalent dose of 0.1 mmol/ kg bodyweight. The improved diagnostic performance is attributable solely to the greater r1 relaxivity of MultiHance; the two-fold higher concentration of Gadovist in the vial is of no diagnostic benefit.


at 1.5T (3.6 L/mmol/sec) [11]. Although the overall conclusion of the study was that significantly higher qualitative and quantitative preference is seen with Gadovist compared to Dotarem, this was by no means the case for all end-points and all readers. Thus, significant prefer- ence for Gadovist compared to Dotarem was noted by only two of three blinded readers in terms of overall reader pref- erence, while none of the three readers considered Gadovist to be superior for lesion delineation. Likewise, only one blinded reader noted minimally sig- nificant preference for Gadovist for the definition of lesion internal structure. In terms of quantitative parameters, no significant difference was noted between the two agents for contrast-to-noise ratio while the difference in mean percent lesion enhancement, although statisti- cally significant, was approximately just 9% for Gadovist compared to Dotarem. Finally, results of an intraindividual


comparison of Gadovist with Pro- Hance, another nonionic macrocyclic contrast agent formulated as a 0.5 M solution, are available on the Food and Drug Administration (FDA) website [22] as part of the development pro- gram for the approval of Gadovist in United States. The study, which was conducted on 419 enrolled patients, demonstrated similar score param- eters for contrast enhancement, border delineation, and internal morphology when these agents were administered at similar dose. Rather than looking to demonstrate significant superiority


APRIL/MAY 2012


for Gadovist compared to ProHance (as performed for all comparative studies involving MultiHance) the study aimed solely at confirming non-inferiority for Gadovist compared to ProHance. The three blinded readers in the study demonstrated a similar accuracy of diagnosis for the two contrast agents, again with Gadovist confirmed as non- inferior to ProHance (as opposed to superior) for all readers.


CONCLUSION


The overall conclusion from these stud- ies is that it is solely the relaxivity of the GBCA that affects the visualization and contrast enhancement of enhancing cerebral lesions. Consistently superior and reproducible results were obtained across all studies only with the con- trast agent with significantly higher relaxivity,


i.e. MultiHance. Thus, the


difference in percent lesion enhance- ment of approximately 9% for Gadovist compared to Dotarem [21] reflects the slightly greater r1 relaxivity of Gadovist compared to Dotarem while the much larger difference of approximately 22% for MultiHance compared to Gadovist [20] reflects the much larger difference in r1 relaxivity between MultiHance and Gadovist. Although these data were obtained at 1.5T it is likely the same will hold true at 3T based on findings for MultiHance compared to Magnevist (a difference in percent lesion enhance- ment of approximately 45% [6]). In summary, the higher concentra- tion of gadolinium in the Gadovist


DI EUROPE


formulation is of minimal, if any, benefit compared to conventional GBCAs for the improved visualization of brain tumors. The slight benefit seen with Gadovist compared to Dotarem can be attributed solely to the slightly higher relaxivity of Gadovist compared to Dotarem and to the fact that Dotarem has the low- est relaxivity of all the available GBCAs. Additionally, no significant differences were shown when Gadovist was com- pared to ProHance; despite the double concentration of Gadovist no significant benefit was seen in terms of clinical or diagnostic effect. Conversely, the results of the MERIT study show that regardless of the two-fold higher concentration of gadolinium in the Gadovist formulation, it is solely the dose administered (i.e. the number of molecules rather than their concentration) that is important. Again the results of the MERIT study demon- strate unequivocally that it the higher relaxivity of MultiHance that makes the difference. These results confirm expectations based on considerations of GBCA molecular structure and physico- chemical properties.


REFERENCES


1. MultiHance Summary of Product Characteristics. : http://www.medicines.org.uk. Accessed 5 October 2011.


2. Knopp MV et al. Radiology 2004; 230: 55.


3. Essig M et al. Academic Radiology 2006; 13: 744.


4. Maravilla K R et al. Radiology 2006; 240: 389. 5. Kuhn MJ et al. J Neurosurg. 2007; 106: 557.


6. Rumboldt Z et al. J Mag Reson Imaging. 2009; 29: 760.


7. Rowley HA Am J Neuroradiol. 2008; 29: 1684.


8. Colosimo C et al. Neuroradiology 2004; 46: 655. 9. Yuh WT et al. Radiology 1991; 180: 485.


10. Pintaske Je t al.Invest Radiol 2006; 41: 213. Erratum in Invest Radiol 2006; 41: 859.


11. Rohrer M et al. Invest Radiol 2005; 40:715- 724.


12. de Haën C et al. J Comp Assist Tomo 1999; 23 (Suppl 1): S161.


13. Cavagna FM et al. Invest Radiol 1997; 32: 780.


14. Giesel FL et al. Invest Radiol 2006; 41: 222.


15. Achenbach M et al. J Mag Res Imaging. 2010; 32: 1166.


16. Gerretsen SC et al. Radiology. 2010; 255: 988.


17. Pediconi F et al. Am J Roentgenol. 2008; 191:1339.


18. Martincich L et al. Radiology. 2011; 258:396 .


19. Achenbach M et al. J Mag Res Imaging. 2010; 32: 1166.


20. Seidl Z et al. Am J Neuroradiol. 2012; March 1 [epub ahead of print]


21. Anzalone N et al. Eur J Radiol. 2011 Sep 2. [Epub ahead of print].


22. Available at: www.accessdata.fda.gov/drug- satfda_docs/nda/2011/201277. Accessed 8 February 2012.


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