P2A-2 A New Model for the Maximum Reflectivity Enhancement from Targeted Contrast Agents

Targeted contrast agents and ultrasound imaging are now used in combination for the assessment and tracking of biomarkers in animal models in-vivo [Lindner, JR, 2004]. These applications have triggered interest in the description and prediction of the echoes from contrast agents bound to cells and vessel walls. A model to predict the reflectivity enhancement of discrete particles bound at low density to a poorly reflective flat surface has been proposed previously [Couture, O, et al., 2006]. This study tries to explain the echo from a surface covered with high concentrations of particles and particles with large scattering cross-sections. It is hypothesized that the reflection coefficient of a surface covered with particles increases with their surface density until reaching saturation which can arise from an interference between layers (interference model) or if the incident beam is fully scattered (Angel´s [Angel, YC, et al.,2005] model). The two models have been tested experimentally with glass beads and with bound microbubbles. Glass beads, which have a scattering cross-section significantly smaller than their geometric cross-section, have been deposited in layers over a poorly reflective surface. Their reflection coefficient was determined, between 10 and 80 MHz, by comparing the echo of these layers of beads with respect to the echo from the reference reflector. The experimental reflection coefficient deviated from linearity when more than 2 layers of particles were present and saturated when more than three layers of beads were present. The interference model also peaked when a third layer of particles was present on the surface. The peak reflectivities determined experimentally and theoretically were 0.38 plusmn 0.02 and 0.42, respectively. Bound microbubbles, which have a scattering cross-section close to their geometric cross-section, have been bound to a surface of gelatin through the avidin-biotin complex. The reflection coefficient was determined for s- urface densities up to a surface coverage of about 20%. The reflection coefficient peaked at 0.8 when 10% of the surface was covered with microbubbles (about 70 microbubbles in the transducer beam area). The multiple scattering model (Angel) corresponded very well to the values of the first trial. This study highlights the interference phenomenon in the reflectivity when several layers are accumulated. It also shows that the reflection coefficient of a surface covered with microbubbles can be higher than that of a polished quartz surface. The two simple models proposed seems capable of predicting the reflectivity coefficient of beads and microbubbles deposited or bound on a surface even at very high concentrations. The fact that it can determine the maximum enhancement from targeted contrast agents might be very useful for choosing the optimal agent for molecular imaging with ultrasound