Microbubbles in imaging: Applications beyond ultrasound

Since their introduction as ultrasound contrast agents, microbubbles have demonstrated the potential to revolutionise the use of ultrasound at the bedside. Aside from clinical application, where microbubbles are used to enhance ultrasonic assessment of myocardial perfusion, they have demonstrated potential in an exciting host of preclinical ultrasound imaging and therapeutic applications. These include the ability to target specific cellular markers of disease, provide dynamic blood flow estimation, deliver localised chemotherapy, potentiate the mechanisms of gene therapy, enhance lesion ablation through cavitation and spatiotemporally permeabilise the blood-brain barrier. The unique and flexible construction of microbubbles not only enables a variety of ultrasound applications, but also opens the door to detection of microbubbles with modalities other than ultrasound. In this review, non-ultrasound imaging applications utilising microbubbles are discussed, including magnetic resonance imaging (MRI), positron emission tomography (PET) and diffraction enhanced X-ray imaging (DEI). These various imaging approaches illustrate novel applications of microbubbles, and may provide the groundwork for future multimodality imaging or image guided therapeutics. In MRI microbubble response has been enhanced by incorporating paramagnetic iron oxide particles into the shell and by use of a hyperpolarised core gas. In PET contrast is achieved with the use of radiolabelling, whereas is DEI scattering at the gas/water interface.