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Encapsulated Microbubbles: From echocardiography to noninvasive blood pressure
monitoring and targeted drug delivery
Kausik Sarkar
Department of Mechanical and Aerospace Engineering,
George Washington University
Micron-size gas bubbles are intravenously injected into a patient’s body to improve the contrast of
ultrasound blood flow images. Currently in the USA, two such contrast agentsOptison (GE Health Care)
and Definity (Lantheus Medical Imaging)are approved by the Food and Drug Administration for
echocardiography. These bubbles are encapsulated by a thin layer (4-10nm) of protein, lipids and other
surface-active materials to prevent their premature dissolution in the blood. They can be chemically
functionalized to attach to target tissues and aid in molecular imaging and targeted delivery. Their
destruction by strong ultrasound pulses is being used in real-time blood flow velocity measurement,
stimulating arteriogenesis (generation of new arteries), and targeted drug delivery. For the past decade, we
have been performing experimental and analytical research on contrast microbubbles. We first proposed
and subsequently developed an interface model of the encapsulationhas an intrinsic surface rheology with
surface viscosities and elasticitiesthat addresses the wide disparity of scales between the overall bubble
size and that of the encapsulation. In this talk, I will discuss material characterization of these contrast
agents that includes determination of rheological properties of a contrast microbubble’s encapsulation using
one set of in vitro experiments, followed by model validation using another set. I will present a hierarchical
approach with increasing sophistication in constitutive modeling of the encapsulation as warranted by the
determining experiments and underlying physics. A new model for the dissolution of microbubbles that
accounts for the effects of encapsulation: the encapsulation hinders the permeability of the gas-liquid
surface, and its elasticity balances the surface tension-induced dissolution stress. We investigate the use
subharmonic signals to noninvasively monitor organ-level blood pressure. I will show and explain unusual
behaviors of subharmonic response in sharp contrast to “plausible expectations” and classical results from
free bubble dynamics. I will also briefly discuss specifically targeted and triggered cytosolic delivery of cancer
drugs from “echogenic liposomes”.
Time permitting, I will provide an overview of other research efforts at our lab. It includes direct numerical
simulation of multiphase flowsemulsions of deformable viscous and viscoelastic drops, capsules, their
rheology, adhesion and migration of leukocytes on active substrates in presence of receptor-ligand
bindingas well as ultrasound mediated bone fracture healing and cancer therapy.