Even though ultrasound remains the safest and the most popular (one in every three imaging in the world) means of imaging, its utility is limited due to poor contrast. 20% of the 17 million echocardiography performed in the United States in 2000 were suboptimal, i.e. did not provide definitive diagnosis for coronary heart disease. Microbubbles intravenously injected into patients’ body can enhance the contrast of ultrasound images. A good contrast agent will enable reliable imaging of abnormal blood flows leading to early diagnosis of heart disease, as well as those of the kidney, liver and brain. They can also deliver drugs to tageted tissues. Current methods of contrast agent design and its use in drug delivery are empirical.
In collaboration with Professor Flemming Forsberg (Thomas Jefferson Medical School) we perform in vitro experiments and develop theoretical models to offer a unique and clear pathway for a rigorous methodology to customize contrast agent design for specific tasks and applications. It will be a useful tool to agent developers (e.g. GE Health Care) and scanner manufacturers (e.g. GE or Phillips). Contrast bubbles are stabilized by a thin encapsulating layer ( ~ 4-10nm) of surface active material, such as protein, lipid or surfactant. The encapsulation plays a critical role in the performance of these agents. In 2003 we first proposed and developed interfacial rheological models for the encapsulation, which has since become popular with the contrast agent reserach community. The encapsulation is treated as an interface having zero thickness and an intrinsic surface rheology (surface viscosity and elasticity). The rationale for our model vis-à-vis ones with a thick layer is the anisotropy and inhomogeneity (in thickness direction) in the molecular structure of the encapsulation. Our hypothesis is that a model, if it retains the essential physics, will offer applicability over a wide range of acoustic excitations. We adopted a two-prongted approach of determination and validation. After we determine the model parameters from one set of experiments, we proceed to validate the model using a different set of experiments. The model is validated by comparing its prediction against the scattered nonlinear (sub- and super-harmonic) response measured at higher amplitudes. We have succesfully applied this approach to model commercialy available agents such as Optison® (Mallinckrodt, St Loius, MO) and Definity® (Bristol Meyer-Squibb Imaging, N. Billerica, MA). Our current focus has been further model development, applicatiosn to newer agents and developing underlying physics of other applications such as subharmonic aided noninvasive pressure estimation (SHAPE).