National Science Foundation - Division of Chemical &Transport Systems Particulate & Multiphase Processes Program (1415)
Proposal Number: 0651912 Principal Investigators: Sarkar, Kausik Affiliation: University of Delaware Proposal Title: Modeling and Characterization of Microbubble Contrast Agents for Medical Imaging and Drug Delivery
Intellectual Merit Microbubbles are injected into a patient's body to enhance the contrast of an ultrasound image. They are also designed to deliver drugs to target tissues. The goal of this proposal is to use experiments and analysis to develop mathematical models, and to characterize these microbubble contrast agents with a view to improving their design. The focus of the effort is on modeling the protective encapsulation of a contrast microbubble made of proteins and lipids, and microbubble breakup under acoustic excitation. New interface models will be developed for the encapsulation with intrinsic surface rheological properties, and these properties will be determined for several contrast microbubbles by in vitro acoustic (attenuation and scattering) experiments. A computational code to simulate large oscillation of a microbubble under ultrasonic excitation will also be developed.
Despite previous attempts, currently there is no reliable model of encapsulated contrast microbubbles which has been systematically validated against experimental observations. A novel acoustic method will be used to determine the interfacial rheology. The same acoustic setup will also be used to investigate the microbubbles' response to ultrasound excitation. The rheological properties of a microbubble will be determined using the attenuation of an ultrasound pulse passing through a microbubble emulsion. The validity of the rheological model, and whether it extends beyond the attenuation data, will be determined by comparing model predictions with the microbubbles' scattered response.
The specific aims of this proposal are: 1. Develop dynamical models of contrast agents. Model a bubble encapsulation as an interface with characteristic surface rheological parameters. Obtain nonlinear bubble dynamics equations. Use them to predict attenuation and scattering of ultrasound in an emulsion of contrast agent. 2. Measure rheological properties of contrast microbubbles and investigate model behaviors. Experimentally determine attenuation and scattering of ultrasound through an emulsion of contrast microbubbles. Use results to validate models. Compare performance with existing models. Modify and implement additional features to improve models. Perform experiments and simulations for varying concentration and excitation parameters (amplitude, frequency and pulse-repetition frequency). 3. Investigate bubble oscillation, stability and destruction. Develop a Boundary Element Method (BEM) based computational code to investigate large deformation of contrast microbubbles. Develop an analytical model of bubble growth and shrinkage due to gas permeation through encapsulation.
Broader Impact Although the 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 echocardiographies performed in the United States in 2000 were suboptimal. A good contrast agent will enable reliable imaging of abnormal blood flows leading to early diagnosis of disease. Current methods of contrast agent design and use are empirical. Our research will help develop a rigorous methodology to customize contrast agent design for specific tasks and applications. The proposal will help train ME undergraduate and graduate students in the non-traditional cross-disciplinary interface of biology and mechanics. The PI has established a link with a collaborator in Morgan State University (an HBCU) to identify talented undergraduate research internships and to groom them for graduate study at UD.
