| Background: Ultrasonography is becoming the first line-imaging tool in the clinical practice because of its low cost, wide availability. But in some clinical conditions, the detail information of the internal structure is especially difficult to distinguish from the surrounding tissue in an ultrasound image without contrast.One approach to enhancing the ultrasound images is to inject a highly echogenic microbubble agent into the venous system, ultrasound interacts much more strongly with microbubbles than other imaging modalities. The combinations of ultrasound and contrast agents improve diagnostic efficiency and increase diagnostic confidence. Contrast ultrasound can improve the image quality to detect and characterize lesions, it may reduce patients referred for higher-priced or invasive procedures. So contrast imaging becomes the research focus spanning several specific fields. For lacking of ideal contrast agent theapplication of contrast ultrasound is limited, so developing a novel ultrasound contrast agent is a promising research work. Because biodegradable polymers are well established in the pharmaceutical, medical and biomedical field as biomaterials for a variety of applications, and can be developed as a hollow microsphere. By changing the polymer compositions, the elasticity and compressibility of the solid shell can be controlled, as a result, the optimal ultrasound property such as attenuation coefficient, backscatter coefficient and second harmonic properties of the microbubbles can be obtained. So polyester microbubble could be a very good candidate as the contrast agent.Objectives: There are four parts in the current dissertation to evaluate the basic characteristics and potential diagnosis value of the novel agent and to evaluate its effects on hemodynanics and pulmonary gas exchange and its microvascular behavior verifying its feasibility and safety to be used as a ultrasound contrast agent (UCA). Methods: the physicochemical properties (bubble inner characteristics concentration, size distribution, and stability) were determined with SEM (scanning electron microscope, laser confocal microscope, andlight microscope). The resistance to pressure and the acoustic properties of the novel polymer agent were evaluated in vitro with a self-made set. Its effects on pulmonary gas exchange and homodynamics were investigated in nine healthy dogs. Its microcirculation rheology characteristics were investigated in Wister rat's mesentery with vital microscope. And pathologic slides were made to exam the effects on important organs such as heart, lung, liver, kidney, and brain. The diagnosis value of the polymer contrast agent was further evaluated in dogs. Left heart image were recorded after injection of different doses of the agent and under different imaging modes with ultrasound energy at a variety of MI values (from 0.1 to 1.5).Result: The polylatone microcapsule was formulated as a lyophilized product, which after addition of saline, provides a suspension containing 1.0 x 109microbubbles/ml,with mean diameter of 1.5 μm, 98 % of the bubbles diameters were below 8μm. It is resistant to pressures such as the ones occurring in the left ventricle. In vitro study this kind of echo-contrast agent showed high echogenicity. Injections in animals provide a homogenous, dose-dependent opacification of theleft ventricle, whereas harmonic imaging increases left ventricle gray intensity by more than five times (p < 0.001) compared with fundamental imaging. And left ventricle gray intensity had a linear relation with ML There was no significant adverse effect on hemodynamics and blood gas analysis; the microcirculation rheology of this kind of microbubble is similar to that of erythrocyte. Conclusion: the above results suggersts that the novel polylatone microcapsule contrast agent is a promising ultrasound contrast agent for its high echogenicity, outstanding stability, and resistance to pressure changes.
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