Production of microbubbles for use as echo contrast agents

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Abstract
A variety of agents have been proposed for use as contrast for ultrasound studies. Several reports suggest the use of microbubbles because of their superior son‐ographic resolution. We describe a method of producing calibrated microbubbles utilizing differential absorption and gas injection techniques. Gas injection methods are described using a Plexiglas® microbubbler apparatus with a fine needle orifice. The bubbles originally produced by this device are in a size range of 40–100 μm and consist of nitrogen (10%) and carbon dioxide (90%). The differential absorption technique uses THAM [tris(hydroxylmethyl)aminomethane hydrochloride] to absorb the carbon dioxide (diluent gas) from the bubbles selectively, leaving smaller microbubbles. The microbubbles can be calibrated using the electric gating principle of the Coulter Counter.