Acoustic Properties of NC100100 and Their Relation With the Microbubble Size Distribution

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Abstract
Sontum PC, Østensen J, Dyrstad K, Hoff L. Acoustic properties of NC100100 and their relation with the microbubble size distribution. Invest Radiol 1999;34:268–275. NC100100 is a contrast agent for medical imaging with ultrasonography consisting of stabilized gas microbubbles in an aqueous suspension. The objective of this article is to explore the acoustic properties of NC100100 and their relation with the microbubble size distribution. The results are used to motivate the choice of a suitable assay/dosage parameter for precise control of product efficacy. The concentration and size distribution of microbubbles in >50 preparations of NC100100 were determined by Coulter counting, and the acoustic attenuation and backscatter efficacy were determined for all samples. The in vivo efficacy of the product was investigated by harmonic imaging of the heart in a dog model. The results demonstrated that the attenuation and backscatter efficacy per microbubble volume vary strongly with size, showing distinct maxima with respect to microbubble diameter. Sizes for optimal attenuation per volume ranged from 2.6 to 5.8 μm, depending on ultrasound frequency. The contribution of the smaller end tail of the microbubble distribution was shown to be negligible. From the observed size dependency for the acoustic properties, the volume concentration of microbubbles was chosen as the assay/dosage parameter for NC100100. The accuracy of this parameter as a descriptor of product efficacy was demonstrated by precise, linear relations between volume, concentration, and attenuation/backscatter. In comparison, the correlation between the microbubble number and acoustic properties was not significant. Results from the in vivo study showed a precise, linear relation between injected microbubble volume and the observed in vivo efficacy. The acoustic properties of NC100100 are dependent on microbubble size. The observed batch-to-batch variance in the acoustic properties of the product may be fully explained by variation in concentration and size. Microbubble volume is a more precise predictor of in vitro/in vivo efficacy than microbubble number and consequently was chosen as the assay/dosage parameter for NC100100.