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

Peter Frinking*, Tim Segers, Ying Luan, François Tranquart

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

168 Citations (Scopus)
233 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)892-908
Number of pages17
JournalUltrasound in medicine and biology
Issue number4
Early online date13 Jan 2020
Publication statusPublished - Apr 2020


  • Contrast agents
  • Definity
  • Microbubbles
  • Monodisperse
  • Optison
  • Sonazoid
  • SonoVue
  • Ultrasound
  • 22/2 OA procedure


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