Smith Denise A B, Porter Tyrone M, Martinez Janet, Huang Shaoling, MacDonald Robert C, McPherson David D, Holland Christy K
Department of Biomedical Engineering, Colleges of Engineering and Medicine, University of Cincinnati, Cincinnati, OH, USA.
Ultrasound Med Biol. 2007 May;33(5):797-809. doi: 10.1016/j.ultrasmedbio.2006.11.017. Epub 2007 Apr 6.
Echogenic liposomes (ELIP) are submicron-sized phospholipid vesicles that contain both gas and fluid. With antibody conjugation and drug incorporation, these liposomes can be used as novel targeted diagnostic and therapeutic ultrasound contrast agents. The utility of liposomes for contrast depends upon their stability in an acoustic field, whereas the use of liposomes for drug delivery requires the liberation of encapsulated gas and drug payload at the desired treatment site. The objective of this study was twofold: (1) to characterize the stability of liposome echogenicity after reconstitution and (2) to quantitate the acoustic destruction thresholds of liposomes as a function of peak rarefactional pressure (P(r)), pulse duration (PD) and pulse repetition frequency (PRF). The liposomes were insonified in an anechoic sample chamber using a Philips HDI 5000 diagnostic ultrasound scanner with a L12-5 linear array. Liposome stability was evaluated with 6.9-MHz fundamental and 4.5-MHz harmonic B-mode pulses at various P(r) at a fixed PRF. Liposome destruction thresholds were determined using 6.0-MHz Doppler pulses, by varying the PD with a fixed PRF of 1.25 kHz and by varying the PRF with a fixed PD of 3.33 micros. Videos or freeze-captured images were acquired during each insonation experiment and analyzed for echogenicity in a fixed region of interest as a function of time. An initial increase in echogenicity was observed for fundamental and harmonic B-mode imaging pulses. The threshold for acoustically driven diffusion of gas out of the liposomes using 6.0-MHz Doppler pulses was weakly dependent upon PRF and PD. The rapid fragmentation thresholds, however, were highly dependent upon PRF and PD. The quantification of acoustic destruction thresholds of ELIP is an important first step in their development as diagnostic and drug delivery agents.
回声脂质体（ELIP）是含有气体和液体的亚微米级磷脂囊泡。通过抗体偶联和药物包封，这些脂质体可用作新型靶向诊断和治疗超声造影剂。脂质体用于造影的效用取决于其在声场中的稳定性，而脂质体用于药物递送则需要在所需治疗部位释放包封的气体和药物载荷。本研究的目的有两个：（1）表征重构后脂质体回声性的稳定性；（2）定量脂质体的声破坏阈值，作为峰值负压（P(r)）、脉冲持续时间（PD）和脉冲重复频率（PRF）的函数。使用配备L12 - 5线性阵列的飞利浦HDI 5000诊断超声扫描仪在消声样品室中对脂质体进行超声照射。在固定PRF下，使用6.9 MHz基波和4.5 MHz谐波B模式脉冲在不同P(r)下评估脂质体稳定性。通过使用6.0 MHz多普勒脉冲，在固定PRF为1.25 kHz时改变PD以及在固定PD为3.33微秒时改变PRF来确定脂质体破坏阈值。在每次超声照射实验期间采集视频或冻结捕获的图像，并分析固定感兴趣区域内回声性随时间的变化。对于基波和谐波B模式成像脉冲，观察到回声性最初增加。使用6.0 MHz多普勒脉冲使气体从脂质体中进行声驱动扩散的阈值对PRF和PD的依赖性较弱。然而，快速破碎阈值高度依赖于PRF和PD。定量ELIP的声破坏阈值是其作为诊断和药物递送剂开发的重要第一步。
