Effects of Temperature on Albunex and FS069 Echocardiographic Contrast Agents: In Vitro Investigation Using Ultrasonic Irradiation

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Abstract
The effects of temperature on the stability of two contrast agents, Albunex and perfluoropropane filled albumin microspheres (FS069), were investigated by studying the variations in their reflective properties, induced by high dose ultrasound irradiation at different temperatures. Diluted contrast agents were introduced into a 3.5-mL latex balloon, placed in a plastic water tank, and continuously irradiated over a period of 6 minutes using different power levels: 0, 20, 25, and 30 dB. The irradiation was interrupted for imaging every 30 seconds for 2 seconds. The protocol was carried out at three different temperatures: 8 degrees C, 22 degrees C, and 37 degrees C. For each temperature, the concentration of contrast solution was matched to produce approximately the same initial video intensity. Time variations in mean video intensity in the balloon cross section were studied. Contrast enhancement was found to be directly related to temperature. Under continuous ultrasonic irradiation, video intensity gradually decreased over time. This decrease was dependent on both transmitted power and temperature, and was more pronounced with Albunex when compared to FS069 (P < 0.05). Abruptly dropping temperature consistently resulted in rapid, irreversible disappearance of contrast induced by Albunex. Temperature affects the reflectivity and stability of diluted Albunex and FS069. To enhance the reproducibility of contrast enhancement achieved by these agents, their temperature should be carefully controlled.

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