Physiologic Factors Affecting the Circulatory Persistence of Copolymer Microbubbles and Comparison of Contrast-Enhanced Effects between Copolymer Microbubbles and Sonovue.

Ultrasound contrast agents have been widely used in clinical diagnosis. Knowledge of the physiologic factors affecting circulatory persistence is helpful in preparing long-lasting microbubbles (MBs) for blood perfusion and drug delivery research. In the study described here, we prepared copolymer MBs, compared their characteristics and contrast-enhanced effects with those of SonoVue and investigated the influence of external pressure, temperature, plasma components, renal microcirculation and cardiac motion on their circulatory persistence. The mean size of the copolymer MBs was 3.57 μm, larger than that of SonoVue. The copolymer MBs had longer circulatory persistence than SonoVue. At external pressures of 110 and 150 mm Hg, neither the quantity nor the morphology of the copolymer MBs changed. Further, their quantity and size were similar after incubation at 4°C and 39.4°C and when rabbit plasma and saline were compared. In vivo contrast-enhanced ultrasonography revealed a slightly larger area under the curve for the renal artery than for the renal vein. Thus, copolymer MBs exhibited good stability. However, the quantity of copolymer MBs decreased significantly after 180 s of circulation in an isolated toad heart perfusion model, indicating that cardiac motion was the main factor affecting their circulatory persistence.