The Constrained Oscillation Theory And The Corresponding Analysis Method Of Microbubbles In Medical Applications

Medical bubbles have been widely applied in ultrasonic imaging (UI), targeted drug delivery (TDD) and shock wave lithotripsy (SWL). But for subgroup patients in these treatments, the injuries of renal tissue and vascular system are caused by bubbles oscillating and rupturing. Therefore, it has theoretical and clinical importance to explore the constraint oscillation mechanicsm of medical microbubbles. In this dissertation, by using the principle of liquid-solid coupled vibration and the method of computational fluid dynamics, the non-spherical oscillation characteristics of a medical microbubble and the corresponding dynamic responses of a micro blood vessel are investigated. Specific innovative contents are as follows:(1) Double-layered structural theory of the ultrasound contrast agent (UCA) and its analysis method are introduced. To obtain excellent scattering ratio and sufficient reliability in UCA, we propose a new double-layered spherical shell structure and obtain the relationship between reflectivity and frequency. We also calculate and analyze the effects of thickness, material coefficients and viscoelastic damping of outer shell on the scattering characteristics of the structure. The results show scattering features of the double-layered shell are remarkably improved by an appropriate soft outer shell in UI.(2) We present an ellipsoidal evolving model of constrained bubble according to the experimental observation in vivo, and construct an asysmmetric oscillation theory to analyze a non-spherical bubble. Computational results show that oscillating bubble profile depends on the liquid and solid boundary conditions, and indicate that the asymmetric effects of bubble oscillation due to the vessel constraint lead to a larger pressure exerted on the vessel, which is obviously underestimated or ignored by the Rayleigh–Plesset equation.(3) We propose a three-phase dynamic model of a bubble-blood-vessel coupled oscillation system with a real constraint blood vessel. Inertial effect and compliance effect of the microvessel are taken into account. Calculated results show that a vessel wall with the thinner vessel or larger circumferential stiffness or higher pre-existing blood pressure correspond to the stronger bubble asymmetric measure and larger vessel stress amplitude. Thus elders, children and some special subjects such as cardiovascular and diabete patients, are higher risk in assisted therapy involving shock waves.(4) The blood viscosity effects in course of constrained bubble oscillating are investigated. It has been proved that asymmetrical oscillation mode is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode.(5) A new dynamic model about a bubble confined inside a double-layer micovessel is proposed, and then the asymmetric oscillation characterists of the microbubble and the regarding stress changes of the vessel are analyzed. It exhibits inconspicuous fluctuation with the asymmetrical scale of bubble oscillation and the liquid pressure exerted on the vessel wall, however, the corresponding dynamic circumferential stress of inner intima layer is increasing acutely. These conclusions indicate that the atherosclerotic patients have a higher risk in SWL.We systematically propose and develop a bubble-liquid-vessel dynamic coupled model about constrained microbubble oscillation inside a micro pseudoelastic blood vessel, and investigate various effects on stresses and deformation of a vessel wall including asymmetric bubble oscillation, blood viscocity and vessel material and geometric papameters. We also prove that asymmetrical oscillation is a primary factor for vascular injury and circumferentially tearing is the dominant rupture mode. These conclusions have significant theory and application importances in safety of TDD and SWL.