Gas-filled microbubbles--a novel susceptibility contrast agent for brain and liver MRI

Gas-filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. However, in vivo demonstration of microbubble susceptibility effect is limited so far and microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (AMBs) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue), were investigated with in vivo dynamic brain and liver MRI in Sprague-Dawley rats at 7 Tesla. Transverse relaxation rate enhancements (DeltaR2*) maps were computed for brain and liver, yielding results similar to those obtained with a common MR blood pool contrast agent. These results indicate that gas-filled microbubbles can serve as an intravascular MR contrast agent at high field. Enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into microbubbles was also investigated at 7 T in vitro. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas-filled microbubble susceptibility effect can be substantially increased using iron oxides nanoparticles. With such approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications.