ABSTRACT
The introduction of microbubbles has significantly changed the field of ultrasound imaging, which previously lacked effective contrast agents compared with other fields of imaging such as computed tomography (CT) or magnetic resonance imaging (MRI), which use iodinated and gadolinium contrast agents, respectively [12, 46]. Microbubbles have been used for a few nonvascular imaging applications, including the assessment of fallopian tube patency in women [121], and vesico-ureteric reflux in children [56]. The majority of diagnostic applications nevertheless involve imaging of the vasculature, be it macro-or microcirculation. Injected intravenously, microbubbles circulate and remain for the most part in the blood pool [54]. Certain microbubble agents have, however, been shown to exhibit tropism by mechanisms that are yet unclear. For example, SonoVue® microbubbles have been shown to exhibit splenic tropism [82], leading to investigations of contrast-enhanced sonography for the imaging of splenic pathologies [106]. The liver tissuespecific phase of microbubbles has been more widely investigated, with Levovist®(Schering AG, Berlin, Germany) being well known as a liver-tropic microbubble [11]. While its strong liver specific phase is an advantage, Levovist is a poor real-time imaging agent, requiring high power output settings that disrupt the microbubbles. Levovist use is therefore being replaced by real-time methods using subsequent generation microbubbles such as SonoVue [4, 136], which are lower mechanical index (MI) agents. Whereas once inferior to CT and MRI in the study of benign and malignant hepatic lesions, the accuracy of ultrasound has now improved significantly with the use of contrast agents [136]. In hepatic malignancies, microbubbles have proven useful not only in diagnostic imaging but also in treatment monitoring [78, 126].While radiology has certainly found a role for ultrasound contrast microbubbles, cardiology is the field of medicine that uses microbubbles most often, with their
primary application in echocardiography for ventricular opacification and delineation of endocardial borders [2, 129]. Other uses have included investigations of carotid artery stenosis [15] and myocardial infarction [61, 84]. As further research explores the potential role of microbubbles in functional imaging of other disease sites such as pleural based lesions [41], the research of microbubbles is also expanding significantly in the field of molecular imaging.
