Ultrasound Imaging Based on Magnetic Lipid Microbubble Contrast Agent with Fe₃O₄ Nanoparticles

To construct magnetic microbubbles with dual response characteristics of ultrasound and magnetic field. The surfactant-based microbubble ultrasound contrast agent (ST68) was prepared using acoustic cavitation. Magnetic Fe₃O₄ nanoparticles having a negative charge on the surface were prepared by the polyol method. The microbubbles were used as the template, and the magnetic microbubbles were prepared by alternating deposition of polyethyleneimine and magnetic Fe₃O₄ nanoparticles on the surface of microbubbles using electrostatic attraction for a layer-by-layer selfassembly. An in vitro ultrasound contrast device was set up to compare the ultrasound images of the silicone tube in the device before and after the injection of human magnetic microbubbles (3×10/M), and to observe the movement of the magnetic microbubbles after the magnetic field was applied to the silicone tube. To evaluate the contrast effect of magnetic microbubbles in vivo, we compared the renal ultrasound images of New Zealand white rabbits before and after injection of human magnetic microbubbles. The surface of Fe₃O₄ nanoparticles displayed a stable negative charge (-24.6±67 mV). More than 98% of the assembled magnetic microbubbles were smaller than 8 μm, which met the basic size requirement for an ultrasound contrast agent. There was no echo signal in the silicone tube before the injection of magnetic microbubbles. Following injection, a solid echo was detected in the silicone tube. After the application of the magnetic field, the magnetic microbubbles migrated in the direction of magnetic field. Contrast-enhanced ultrasound did not image the kidney before the injection of magnetic microbubbles, while the kidney shadow was clear following injection. Magnetic targeted microbubbles and contrast-enhanced ultrasound provide good imaging, which lays the foundation for further studies of magnetic targeted microbubble contrast agents in diagnosis and treatment.