Influence of Bubble Size Distribution on the Echogenicity of Ultrasound Contrast Agents: a Study of SonoVue

Rationale And Objectives: To study the relative contributions of different bubble size classes to SonoVue's echogenicity in fundamental acoustic imaging modes. SonoVue is a contrast agent, previously known as BR1, with a bubble size distribution extending from approximately 0.7 to 10 microm.

Methods: A model for the acoustic response of SonoVue was determined and validated for a set of experimental data. This model was used to simulate the acoustic response of a standard batch of SonoVue as the sum of responses of non-overlapping bubble size classes.

Results: The simulation was first validated for a standard SonoVue bubble size distribution. When this distribution was considered as five size classes with equal numbers of bubbles, it was found that bubbles smaller than 2 microm accounted for 60% of the total number but contained only 5% of the total gas volume. The simulation results indicated marked differences in the acoustic contributions from these classes, with 80% of the acoustic efficacy provided by bubbles 3 to 9 microm in diameter. The study also compared bubble distributions in number, surface, and volume, with the distribution computed in terms of acoustic efficacy.

Conclusions: This study shows why bubble volume is a much better indicator of SonoVue's efficacy than is bubble count. A low threshold in diameter was found for SonoVue microbubbles at approximately 2 microm, under which size bubbles do not contribute appreciably to the echogenicity at medical ultrasound frequencies.