Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0586, USA.
Ultrasound Med Biol. 2012 Nov;38(11):1970-81. doi: 10.1016/j.ultrasmedbio.2012.06.012. Epub 2012 Aug 25.
Echogenic liposomes (ELIP) are multifunctional ultrasound contrast agents (UCAs) with a lipid shell encapsulating both air and an aqueous core. ELIP are being developed for molecular imaging and image-guided therapeutic delivery. Stability of the echogenicity of ELIP in physiologic conditions is crucial to their successful translation to clinical use. In this study, we determined the effects of the surrounding media's dissolved air concentration, temperature transition and hydrodynamic pressure on the echogenicity of a chemically modified formulation of ELIP to promote stability and echogenicity. ELIP samples were diluted in porcine plasma or whole blood and pumped through a pulsatile flow system with adjustable hydrodynamic pressures and temperature. B-mode images were acquired using a clinical diagnostic scanner every 5 s for a total duration of 75 s. Echogenicity in porcine plasma was assessed as a function of total dissolved gas saturation. ELIP were added to plasma at room temperature (22 °C) or body temperature (37 °C) and pumped through a system maintained at 22 °C or 37 °C to study the effect of temperature transitions on ELIP echogenicity. Echogenicity at normotensive (120/80 mmHg) and hypertensive pressures (145/90 mmHg) was measured. ELIP were echogenic in plasma and whole blood at body temperature under normotensive to hypertensive pressures. Warming of samples from room temperature to body temperature did not alter echogenicity. However, in plasma cooled rapidly from body temperature to room temperature or in degassed plasma, ELIP lost echogenicity within 20 s at 120/80 mmHg. The stability of echogenicity of a modified ELIP formulation was determined in vitro at body temperature, physiologic gas concentration and throughout the physiologic pressure range. However, proper care should be taken to ensure that ELIP are not cooled rapidly from body temperature to room temperature as they will lose their echogenic properties. Further in vivo investigations will be needed to evaluate the optimal usage of ELIP as blood pool contrast agents.
声振脂质体（ELIP）是一种多功能超声对比剂（UCA），具有包裹空气和水相核心的脂质外壳。ELIP 正在开发用于分子成像和图像引导的治疗传递。ELIP 在生理条件下的声振稳定性对于它们成功转化为临床应用至关重要。在这项研究中，我们确定了周围介质溶解气体浓度、温度转变和流体动力学压力对化学修饰的 ELIP 制剂声振性的影响，以促进其稳定性和声振性。ELIP 样品用猪血浆或全血稀释，并在具有可调节流体动力学压力和温度的脉动流系统中泵送。使用临床诊断扫描仪每隔 5s 采集一次 B 模式图像，总持续时间为 75s。在猪血浆中评估 ELIP 的声振性作为总溶解气体饱和度的函数。ELIP 在室温（22°C）或体温（37°C）下添加到血浆中，并在维持在 22°C 或 37°C 的系统中泵送，以研究温度转变对 ELIP 声振性的影响。测量正常血压（120/80mmHg）和高血压压力（145/90mmHg）下的声振性。在正常血压至高血压压力下，ELIP 在体温下在血浆和全血中具有声振性。从室温升高到体温不会改变声振性。然而，在从体温快速冷却到室温的血浆或脱气血浆中，ELIP 在 120/80mmHg 下 20s 内失去声振性。在体温、生理气体浓度和整个生理压力范围内，对改良 ELIP 制剂的声振稳定性进行了体外测定。然而，应注意确保 ELIP 不会从体温快速冷却到室温，因为它们会失去声振特性。还需要进一步的体内研究来评估 ELIP 作为血池对比剂的最佳使用。
