Acoustic properties of NC100100 and their relation with the microbubble size distribution

RATIONALE AND OBJECTIVES. NC100100 is a contrast agent for medical imaging with ultrasonography consisting of stabilized gas microbubbles in an aqueou s suspension, The objective of this article is to explore the acoustic prop erties of NC100100 and their relation with the microbubble size distributio n, The results are used to motivate the choice of a suitable assay/dosage p arameter for precise control of product efficacy, METHODS. The: concentration and size distribution of microbubbles in >50 pr eparations of NC100100 mere determined by Coulter counting, and the acousti c attenuation and backscatter/efficacy were determined for all samples, The in vivo efficacy of the product was investigated by harmonic imaging of th e heart in a dog model, RESULTS. The results demonstrated that the attenuation and backscatter effi cacy per microbubble volume vary strongly with size, showing distinct maxim a with respect to microbubble diameter, Sizes for optimal attenuation per v olume ranged from 2.6 to 5.8 mu m, depending on ultrasound frequency, The c ontribution of the smaller end tail of the microbubble distribution was sho wn to be negligible, From the observed size dependency for the acoustic pro perties, the volume concentration of microbubbles was chosen as the assay/d osage parameter for NC100100. The accuracy of this parameter as a descripto r of product efficacy was demonstrated by precise, linear relations between volume, concentration, and attenuation/backscatter. In comparison, the cor relation between the microbubble number and acoustic properties was not sig nificant, Results from, the in vivo study showed a precise, linear relation between injected microbubble volume and the observed in vivo efficacy, CONCLUSIONS. The acoustic properties of NC100100 are de; pendent on microbu bble size. The observed batch-to-batch variance in the acoustic properties of the product may be fully explained by variation in concentration and siz e. Microbubble volume is a more precise predictor of in vitro/in vivo effic acy than microbubble number and consequently was chosen as the assay/dosage parameter fur NC100100.