Automated Production and Analysis of Echo Contrast Agents

To develop and standardize contrast agents for use in contrast echocardiographic imaging, microbubble size, concentration, decay, and ultrasound backscatter must be known. These parameters were assessed with a scanning laser particle counter, a commercial ultrasound unit, and various sonicated intravenous solutions. The scanning laser particle counter proved to be a fast and effective means of evaluating microbubble size, concentration, and stability. In addition, sonication was found to be a reliable and reproducible technique for preparing standardized echo contrast agent solutions containing uniformly small microbubbles. The bubbles generated ranged in size from 1 to 15 micron in diameter. All solutions had mean bubble diameters less than 6 micron. The half life of solutions ranged from 44 +/- 12 seconds for Hypaque 50%, to 253 +/- 73 seconds for Iopamidol. Addition of the surfactant to dextrose 70% prolonged bubble half life from 58 +/- 12 seconds to 1018 +/- 276 seconds. Phased array two-dimensional echocardiography of sonicated microbubble solutions, and subsequent videodensitometric analysis, revealed that bubble concentration was directly proportional to echo-reflective properties, and that the solutions have significant ultrasound reflective properties in vitro at concentrations of less than 1500 bubbles/ml.