Three Decades of Ultrasound Contrast Agents: A Review of the Past, Present and Future Improvements

Abstract

Initial reports from the 1960s describing the observations of ultrasound contrast enhancement by tiny gaseous bubbles during echocardiographic examinations prompted the development of the first ultrasound contrast agent in the 1980s. Current commercial contrast agents for echography, such as Definity, Optison, Sonazoid and SonoVue, have proven to be successful in a variety of on-and off-label clinical indications. Whereas contrast-specific technology has seen dramatic progress after the introduction of the first approved agents in the 1990s, successful clinical translation of new developments has been limited during the same period, while understanding of microbubble physical, chemical and biologic behavior has improved substantially. It is expected that for a successful development of future opportunities, such as ultrasound molecular imaging and therapeutic applications using microbubbles, new creative developments in microbubble engineering and production dedicated to further optimizing microbubble performance are required, and that they cannot rely on bubble technology developed more than 3 decades ago.

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma

“…In contrast-enhanced ultrasound (CEUS), echogenic particles such as microbubbles are administered to obtain information on vascularization or delineation of body cavities during ultrasound (US) imaging. FDA and EMA approved microbubbles consist of perfluorocarbons or sulfur hexafluoride (SF 6 ) gas surrounded by a thin biocompatible shell generally made of phospholipids or proteins [ 77 , 78 ]. Due to their compressibility and the large difference in acoustic impedance between gas and the surrounding liquid (i.e., blood or lymph) they strongly scatter ultrasound pulses.…”

The value of transvaginal 4-dimensional hysterosalpingo-contrast sonography in predicting the necessity of assisted reproductive technology for women with tubal factor infertility

“…However, this view is still controversial, and a large-scale prospective study is needed for verification (55). Nevertheless, there is no doubt that using the contrast agent, perfluoropropane-albumin microsphere in TV 4D HyCoSy not only plays a part in flushing and dredging the fallopian tube, but can also improve blood supply and promote the absorption of inflammation, while the use of an oil-based contrast agent may impose potential negative effects on thyroid function and neurodevelopment (56,57). Overall, TV 4D HyCoSy is a safe inspection method that does not impinge on pregnancy and fetal outcomes (58).…”

Effect of a Radiotherapeutic Megavoltage Beam on Ultrasound Contrast Agents

“…Ultrasound contrast agents (UCAs) together with ultrasound imaging were proposed as a new method to determine the delivered dose (Verboven et al 2014). The UCAs used for clinical imaging are suspensions of microbubbles coated with a viscoelastic layer that produce strong echoes, compared with tissue, when they are imaged using ultrasound (Frinking et al 2020). When a difference in the acoustics of UCA populations was measured after radiotherapeutic irradiation (Verboven et al 2014), it was hypothesized that this difference could be detected by means of an acoustic imaging device and subsequently related to the radiation dose delivered.…”