Acoustic properties of NC100100 (SONAZOIDTM) and their relationship with the microbubble size distribution: “motivation for choice of assay and dosage parameter”

NC100100 (SONAZOID^TM) is a new contrast agent for ultrasonography consisting of surfactant stabilised perfluorocarbon microbubbles in aqueous suspension. By use of custom developed in vitro sonometry techniques, we have studied relations between the acoustic properties of NC100100 and the microbubble size distribution. By comparing measurements to theoretical predictions of the attenuation spectrum, the authors found that NC100100 microbubbles with a diameter of 3.5 μm may be described by a bulk modulus and volume viscosity of 0.6 MPa and 0.015 Pa s, respectively. Using these values in theoretical expressions the authors found that the extinction and scattering cross sections per microbubble volume varies strongly with size, showing distinct maxima with respect to microbubble diameter. Sizes for optimal backscatter per volume were found to 2.9 and 5.3 μm, for 5.0 and 2.0 MHz, respectively. Utilising multivariate partial least square regression methods, the predictions from the theoretical model were verified by empirical observations. The results were used to motivate the choice of the microbubble volume concentration as assay and dosage parameter for NC100100. The relevance of this choice was demonstrated by in vitro analysis of more than 50 batches of NC100100, resulting in relatively precise linear correlations between microbubble volume and the acoustic attenuation, fundamental and second harmonic backscatter. In comparison the correlations between these acoustic properties and the microbubble number concentration of the same batches was not significant. These findings were confirmed in vivo in a second harmonic study of myocardial perfusion in dog hearts