Generating precision microbubbles for use as an echocardiographic contrast agent

To investigate whether precision microbubbles can be simply generated and used for quantitative contrast echocardiographic studies, precision microbubbles were fabricated in gelatin using a simple generator. The generator consisted of a fluid pump, a generating site containing a narrow bore tube and a bubble stream output port. Up to 5,000 microbubbles/s were generated with a controllable radius of 80 to 150 mu. No detectable interbubble size variation was observed under high power microscopy. To examine whether these bubbles could be used for quantitative contrast echocardiographic studies, they were then infused into a tube with a known flow of degassed water during ultrasonic imaging. The resulting ultrasonic contrast effect in the tube lumen at steady state was recorded and subsequently measured by videodensitometry. The precision microbubbles were visually and microscopically stable during the experimental run. Correlations between microbubble infusion rate and luminal videodensitometry on individual runs were r = 0.89, 0.83, 0.73 and 0.71. It is concluded that precision microbubbles can be generated in sufficient quantities on site to serve as an echocardiographic contrast agent for quantitative studies in vitro and at a very modest cost. These precision microbubbles are sufficiently stable to be collected and stored for short periods of time.