Superparamagnetic iron oxide nanoparticle-embedded encapsulated microbubbles as dual contrast agents of magnetic resonance and ultrasound imaging

An encapsulated microbubble (EMB) of a novel construct is proposed to enhance the magnetic resonance imaging contrast by introducing superparamagnetic iron oxide (SPIO) nanoparticles (mean diameter is 12 nm) into the polymer shell of the microbubble. Such microbubble vesicle has nitrogen gas in the core and its mean diameter is 3.98 μm. An in vitro MR susceptibility experiment using a phantom consisting EMBs has shown that the relationship between the transverse relaxation rate R2 and the Fe3O4 nanoparticle concentration in the shell (the volume fraction of EMBs is kept constant) can be fitted to a linear function and an exponentially growth function is observed between R2 and the SPIO-inclusion microbubble concentration. The in vivo MRI experiments also show that the SPIO-inclusion microbubbles have longer contrast-enhancement duration time in rat liver than non-SPIO-inclusion microbubbles. An in vitro ultrasound imaging experiment of SPIO-inclusion microbubbles also shows that they can enhance the ultrasound contrast significantly. Additionally, the interaction between the SPIO-inclusion microbubbles and cells indicates that such microbubble construct can retain the acoustic property under the ultrasound exposure by controlling the SPIO concentration in the shell. Therefore, the proposed SPIO nanoparticle-embedded EMBs potentially can become effective MR susceptibility contrast agents while also can be good US contrast agents.