Cardiac Magnetic Resonance Angiography using Blood-Pool Contrast Agents: Comparison of Citrate-Coated Very Small Superparamagnetic Iron Oxide Particles with Gadofosveset Trisodium in Pigs

Abstract

Purpose: To compare citrate-coated very small superparamagnetic iron oxide particles (VSOP) with gadofosveset trisodium as blood pool contrast agents for cardiac magnetic resonance angiography (CMRA) in pigs.

Materials and Methods: Animal experiments were approved by the responsible authority. 10 CMRA-like examinations were performed at 1.5 T after administration of VSOP (0.06 mmol Fe/kg; 5 examinations) and gadofosveset trisodium (0.03 mmol Gd/kg; 5 examinations). The CMRA protocol included ECG-gated inversion-recovery-prepared T1-weighted gradient echo imaging (IR-GRE; one slice) and ECG-gated inversion recovery prepared steady state free precession imaging (IR SSFP; one slice) before and 1, 3, 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after injection. At each time point, three different inversion times (TI; 200 msec, 300 msec, and 400 msec) were applied. Contrast-to-noise ratios (CNR) between blood and myocardium were calculated and compared using mixed linear models.

Results: No significant differences of CNR were found between IR-GRE and IR SSFP. At 3 and 5 min after contrast agent administration, VSOP showed a significantly higher CNR than gadofosveset trisodium when TI of 200 msec and 300 msec were applied (TI of 200 msec at 3 min: 8.2 ± 0.7 vs. 5.4 ± 0.7; TI of 200 msec at 5 min: 7.9 ± 0.7 vs. 3.5 ± 0.8; TI of 300 msec at 3 min: 11.7 ± 0.7 vs. 8.8 ± 0.8; TI of 300 msec at 5 min: 11.4 ± 0.7 vs. 8.0 ± 0.8; p < 0.05). Moreover, significant differences in favor of VSOP were found for all time points from 10 to 40 min irrespective of TI (p < 0.05).

Conclusion: VSOP has superior blood-pool properties compared to gadofosveset trisodium resulting in prolonged improvement of CNR on CMRA.

Zusammenfassung

Ziel: Vergleich von citratbeschichteten sehr kleinen superparamagnetischen Eisenoxidpartikeln (VSOP) mit Gadofosveset Trisodium als Blutpool-Kontrastmittel zur kontrastverstärkten Magnetresonanzangiografie des Herzens (CMRA) am Schwein.

Material und Methoden: Nach entsprechender Genehmigung des Tierexperiments wurden 10 CMRA-Untersuchungen bei 1,5 T nach Gabe von VSOP (0,06 mmol Fe/kg; 5 Untersuchungen) und Gadofosveset Trisodium (0,03 mmol Gd/kg; 5 Untersuchungen) durchgeführt. Das CMRA-Protokoll beinhaltete eine EKG-getriggerte, Inversion-Recovery-präparierte T1-gewichtete Gradientenecho-Sequenz (IR-GRE; eine Schicht) und eine EKG-getriggerte, Inversion-Recovery-präparierte Steady-State-Free-Precession-Sequenz (IR-SSFP; eine Schicht) vor und 1, 3, 5, 10, 15, 20, 25, 30, 40, 50 sowie 60 min nach Kontrastmittelgabe. Zu jedem Zeitpunkt wurden 3 verschiedene Inversionszeiten (TI; 200 ms, 300 ms und 400 ms) angewendet. Das Verhältnis von Kontrast zu Rauschen (CNR) zwischen Blut und Myokard wurde berechnet und unter Verwendung gemischter linearer Regressionsmodelle verglichen.

Ergebnisse: In Bezug auf das CNR bestand zwischen IR-GRE und IR-SSFP kein signifikanter Unterschied. 3 und 5 min nach Kontrastmittelgabe zeigte VSOP bei TI von 200 ms und 300 ms ein signifikant höheres CNR als Gadofosveset Trisodium (TI von 200 ms nach 3 Minuten: 8,2 ± 0,7 vs. 5,4 ± 0,7; TI von 200 ms nach 5 min: 7,9 ± 0,7 vs. 3,5 ± 0,8; TI von 300 ms nach 3 min: 11,7 ± 0,7 vs. 8,8 ± 0,8; TI von 300 ms nach 5 min: 11,4 ± 0,7 vs. 8,0 ± 0,8; p < 0,05). Daneben war das CNR von VSOP unabhängig von TI zu jedem Zeitpunkt zwischen 10 und 40 Minuten signifikant höher (p < 0,05).

Schlussfolgerung: Im Vergleich zu Gadofosveset Trisodium hat VSOP einen ausgeprägteren Blutpool-Effekt mit einem anhaltend höheren CNR in der CMRA.

Key words

experimental study - contrast agents - heart - blood vessels

• References

• 1 Lauffer RB, Parmelee DJ, Dunham SU et al. MS-325: albumin-targeted contrast agent for MR angiography. Radiology 1998; 207: 529-538
• 2 Port M, Corot C, Violas X et al. How to compare the efficiency of albumin-bound and nonalbumin-bound contrast agents in vivo: the concept of dynamic relaxivity. Invest Radiol 2005; 40: 565-573
• 3 Bluemke DA, Stillman AE, Bis KG et al. Carotid MR angiography: phase II study of safety and efficacy for MS-325. Radiology 2001; 219: 114-122
• 4 Corot C, Violas X, Robert P et al. Comparison of different types of blood pool agents (P792, MS325, USPIO) in a rabbit MR angiography-like protocol. Invest Radiol 2003; 38: 311-319
• 5 Goyen M, Shamsi K, Schoenberg SO. Vasovist-enhanced MR angiography. Eur Radiol 2006; 16: B9-B14
• 6 Prompona M, Cyran C, Nikolaou K et al. Contrast-enhanced whole-heart MR coronary angiography at 3.0 T using the intravascular contrast agent gadofosveset. Invest Radiol 2009; 44: 369-374
• 7 Wagner M, Rief M, Asbach P et al. Gadofosveset trisodium-enhanced magnetic resonance angiography of the left atrium – a feasibility study. Eur J Radiol 2010; 75: 166-172
• 8 Wagner M, Rosler R, Lembcke A et al. Whole-heart coronary magnetic resonance angiography at 1.5 Tesla: does a blood-pool contrast agent improve diagnostic accuracy?. Invest Radiol 2011; 46: 152-159
• 9 Taupitz M, Schnorr J, Abramjuk C et al. New generation of monomer-stabilized very small superparamagnetic iron oxide particles (VSOP) as contrast medium for MR angiography: preclinical results in rats and rabbits. J Magn Reson Imaging 2000; 12: 905-911
• 10 Wagner S, Schnorr J, Pilgrimm H et al. Monomer-coated very small superparamagnetic iron oxide particles as contrast medium for magnetic resonance imaging: preclinical in vivo characterization. Invest Radiol 2002; 37: 167-177
• 11 Allkemper T, Bremer C, Matuszewski L et al. Contrast-enhanced blood-pool MR angiography with optimized iron oxides: effect of size and dose on vascular contrast enhancement in rabbits. Radiology 2002; 223: 432-438
• 12 Taupitz M, Schnorr J, Wagner S et al. Coronary MR angiography: experimental results with a monomer-stabilized blood pool contrast medium. Radiology 2002; 222: 120-126
• 13 Taupitz M, Wagner S, Schnorr J et al. Phase I clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging. Invest Radiol 2004; 39: 394-405
• 14 Wagner M, Wagner S, Schnorr J et al. Coronary MR angiography using citrate-coated very small superparamagnetic iron oxide particles as blood-pool contrast agent: Initial experience in humans. J Magn Reson Imaging 2011;
• 15 Rohrer M, Bauer H, Mintorovitch J et al. Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol 2005; 40: 715-724
• 16 Schnorr J, Wagner S, Ebert W et al. MR-Angiographie der Koronararterien: Vergleich des Blutpoolkontrastmittels Gadomer mit Gd-DTPA am Schwein. Fortschr Röntgenstr 2003; 175: 822-829
• 17 Li D, Zheng J, Weinmann HJ. Contrast-enhanced MR imaging of coronary arteries: comparison of intra- and extravascular contrast agents in swine. Radiology 2001; 218: 670-678
• 18 Fink C, Goyen M, Lotz J. Magnetic resonance angiography with blood-pool contrast agents: future applications. Eur Radiol 2007; 17: B38-B44
• 19 Stuber M, Botnar RM, Danias PG et al. Contrast agent-enhanced, free-breathing, three-dimensional coronary magnetic resonance angiography. J Magn Reson Imaging 1999; 10: 790-799
• 20 Huber ME, Paetsch I, Schnackenburg B et al. Performance of a new gadolinium-based intravascular contrast agent in free-breathing inversion-recovery 3D coronary MRA. Magn Reson Med 2003; 49: 115-121
• 21 de Haen C, Anelli PL, Lorusso V et al. Gadocoletic acid trisodium salt (b22956/1): a new blood pool magnetic resonance contrast agent with application in coronary angiography. Invest Radiol 2006; 41: 279-291
• 22 Herborn CU, Barkhausen J, Paetsch I et al. Coronary arteries: contrast-enhanced MR imaging with SH L 643A – experience in 12 volunteers. Radiology 2003; 229: 217-223
• 23 Dirksen MS, Lamb HJ, Kunz P et al. Improved MR coronary angiography with use of a new rapid clearance blood pool contrast agent in pigs. Radiology 2003; 227: 802-808
• 24 Taupitz M, Schmitz S, Hamm B. Superparamagnetische Eisenoxidpartikel: Aktueller Stand und zukünftige Entwicklungen. Fortschr Röntgenstr 2003; 175: 752-765
• 25 Weissleder R, Elizondo G, Wittenberg J et al. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 1990; 175: 489-493
• 26 Warmuth C, Schnorr J, Kaufels N et al. Whole-heart coronary magnetic resonance angiography: contrast-enhanced high-resolution, time-resolved 3D imaging. Invest Radiol 2007; 42: 550-557
• 27 Stark DD, Weissleder R, Elizondo G et al. Superparamagnetic iron oxide: clinical application as a contrast agent for MR imaging of the liver. Radiology 1988; 168: 297-301
• 28 Kaufels N, Korn R, Wagner S et al. Magnetic resonance imaging of liver metastases: experimental comparison of anionic and conventional superparamagnetic iron oxide particles with a hepatobiliary contrast medium during dynamic and uptake phases. Invest Radiol 2008; 43: 496-503
• 29 Schnorr J, Wagner S, Abramjuk C et al. Focal liver lesions: SPIO-, gadolinium- and ferucarbotran-enhanced dynamic T1-weighted and delayed T2-weighted MR imaging in rabbits. Radiology 2006; 240: 90-100