Introduction

Contrast agents are used in all imaging modalities to increase the sensitivity of the imaging technique by altering the image contrast between different structures. Ultrasonic contrast agents are composed of a solution of gas-filled microbubbles. It is the dramatic increase in scattering which can be achieved with these microbubbles which has made them useful both in difficult-to-image patients and in areas for which the ultrasound signal is reduced. Injection of the contrast microbubbles and observation of their real-time passage in an ultrasound image can significantly improve the sensitivity and diagnostic power of ultrasonic imaging.

Ultrasonic contrast agents were initially used by a cardiologist in the 1960s, who used physiological saline as an intra-cardiac ultrasound contrast medium in the anatomic identification of mitral valve echoes. Microbubbles, formed in the saline after shaking, increased the contrast in the images. Intravenously injected agitated saline is still used today in cardiac studies in the assessment of patent foramen ovale. However, it was not until the mid-1980s that clinical interest resulted in development of a wide range of potential ultrasound contrast agents, some of which were the early precursors of current commercially available contrast agents. A history of the early development of ultrasonic contrast agents can be found in Ophir and Parker (1989).