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.

Nonlinear propagation effects on broadband attenuation measurements and its implications for ultrasonic tissue characterization.

A study is presented in which the influence of the pressure amplitude of the incident pulse on the estimated frequency dependency of the attenuation coefficient is shown. First, the effect is demonstrated with a simple theoretical model for both transmission and reflection measurements. Simulations show that for both measurement techniques a high-amplitude incident pulse results in a biased estimate of the attenuation coefficient due to nonlinear interaction of the different frequency components of the incident pulse. It is shown that in transmission and reflection measurements the biases have opposite signs. The effect of bandwidth, central frequency, and phase of the incident pulse on this bias is investigated. Second, the effect is demonstrated both in vitro, using a broadband through-transmission substitution technique on a tissue mimicking gelatine phantom, and in vivo, using reflection measurements with standard clinical equipment. The experimental results agree well with the theoretical model. The relevance of this study for ultrasonic tissue characterization is shown.

Estimation of three-dimensional cardiac velocity fields: assessment of a differential method and application to three-dimensional CT data.

We have investigated an optical flow method for the estimation of the three-dimensional endocardial wall motion from high-resolution X-ray CT data. This method was originally proposed by Song and Leahy. It is based on the optical flow, the divergence-free and the smoothness constraints. Due to the characteristics of the imaging modality, we studied the restriction of this approach to the boundary of the left ventricular (LV) cavity. The behaviour of the method is quantified through simulations approximating the overall motion of the LV cavity through an affine transform involving a dilation and a rotation. The method implies the choice of three parameters weighting the constraints. The results show a weak dependence of the velocity field on the weighting of the optical flow constraint. The accuracy of the method relies more heavily on the relative weighting of the smoothness and divergence-free constraints. In our experiments, the best results were obtained for a largely predominant divergence-free constraint. The results also show that the accuracy of the method is reasonable for low values of the rotation angle (minimum mean error of 1.1 voxel for 5 degrees). This is compatible with values reported in other studies for the overall rotation of the LV. We provide a qualitative description of the results obtained in vivo on a canine heart by visualizing the distribution of the estimated velocity vector magnitudes over the endocardial surface. These results (evolution of the field over time, maximum velocities) are in agreement with the known physiological behaviour of the heart.