First‐pass and equilibrium‐MRA of the aortoiliac region with a superparamagnetic iron oxide blood pool MR contrast agent (SH U 555 C): results of a human pilot study

Abstract

The purpose of this study was to study different doses for first-pass and equilibrium phase MRA of aortoiliac vessels with a superparamagnetic iron oxide (SPIO) intravascular MR contrast agent (SH U 555 C) after single i.v. bolus injection. Sixteen healthy volunteers were prospectively enrolled into this single-blind, placebo-controlled clinical trial. SHU 555 C was injected as an i.v. bolus at stepwise increased dose levels of 5, 10, 20 and 40 mmol Fe/kg bodyweight (b.w.) corresponding to injection volumes of 0.01, 0.02, 0.04 and 0.08 ml/kg b.w. Serial high-resolution three-dimensional MRA of the aortoiliac vessels was acquired during first-pass and equilibrium, at 6 min intervals up to 42 min after contrast application using a breath-hold three-dimensional FLASH sequence on a 1.5 T scanner. Intravascular enhancement was calculated within the abdominal aorta and the inferior vena cava and a statistical analysis for significant differences in vessel enhancement was performed during the bolus and equilibrium phases. The visibility of vessels was ranked and effects of potential artifacts on image quality were graded for each time point and dose group. SH U 555 C showed a dose-dependent intravascular enhancement during the observation period (42 min). The highest dose of 40 mmol Fe/kg b.w. revealed the highest image quality during first-pass and equilibrium phases. The intravascular enhancement in the aorta increased dose-dependently from 5 to 40 mmol/kg b.w. during first-pass and equilibrium phases ( p < 0.05). Intravascular signal inhomogeneities were observed at lower doses and decreased with increasing doses. First-pass MRA was diagnostic at doses of 10, 20 and 40 mmol Fe/kg b.w. For equilibrium MRA, a dose of 40 mmol Fe/kg b.w. was considered to be diagnostic. SH U 555 C proved to be a contrast agent with a high T 1 -effect suitable for both first-pass MRA comparable to gadolinium-enhanced MRA and high resolution equilibrium MRA up to 42 min post-injection (p.i.).

The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages

“…Blood pool agents, i. e. intravascular contrast agents including SupravistÔ remain in the blood compartment for a prolonged period of time compared to conventional contrast agents, which diffuse quickly into the interstitial space. Magnetic resonance angiography, cardiovascular imaging, or contrast enhanced MRI are possible over an hour or more upon intravascular injection of such a contrast agent [14,15].…”

Characterization of carotid artery plaques with USPIO-enhanced MRI: assessment of inflammation and vascularity as in vivo imaging biomarkers for plaque vulnerability

“…The USPIO SHU 555 C has been proposed for CE-MRA and allows in contrast to Ferumoxtran-10, for first-pass CE-MRA [32]. In a study of the aorto-iliac vessels by Tombach et al [32] SHU 555 C proved to be a contrast agent with a high T1-effect suitable for both first-pass MRA comparable to gadoliniumenhanced MRA and high resolution equilibrium MRA up to 42 min post-injection. Accordingly, our results showed a diagnostic relevant image quality for first-pass CE-MRA of the supra-aortal vessels.…”

“…Due to prior performance of first-pass CE-MRA, the early plaque perfusion was missed. Another possible approach is to perform DCE-MRI first, followed by equilibrium CE-MRA, which has been reported to be diagnostic for the aorto-iliac region [32], but is yet to be proven for the supra-aortal vessels. USPIO suffer in general from very low absolute T1-w signal enhancement due to low rates of contrast agent extravasation [20].…”

“…The blood-pool half-life time of SHU 555 C was reported to be 7-8 h in humans. SHU 555 C is currently evaluated in clinical trials and little safety data is yet available, but a similar safety profile to Ferucarbotran is expected [31,32]. SHU 555 C was applied at a total dose of 40 lmol Fe/kg body weight (BW), corresponding to an injection volume of mean 5.9 ml in this study.…”

Tumor blood vessel visualization

“…This technique improved significantly the signal-to-noise ratio, particularly in anatomical cortical vascular imaging (Burgess et al, 1999), by achieving resolutions of vessels of around 100 mm in diameter (Dashner et al, 2004). In combination with ultrasmall superparamagnetic iron oxide (USPIO) blood pool contrast agents which remain intravascular for a long period of time (Weissleder et al, 1990;Tombach et al, 2004), an improved capability of data in terms of resolution can be achieved. In a study of Christoforides et al, (Christoforidis et al, 2009) not only vessels with diameters of 20 mm were identified after USPIO administration in an UHF MRI approach but also the state of hypoxia within the tumor was determined.…”