Mechanical Engineering, University of Delaware, Newark, DE 19716, United States.
Ultrasonics. 2012 Sep;52(7):962-9. doi: 10.1016/j.ultras.2012.03.007. Epub 2012 Mar 29.
Echogenic liposomes (ELIP) are an excellent candidate for concurrent imaging and drug delivery applications. They combine the advantages of liposomes-biocompatibility and ability to encapsulate both hydrophobic and hydrophilic drugs-with strong reflections of ultrasound. The objective of this study is to perform a detailed in vitro acoustic characterization - including nonlinear scattering that has not been studied before - along with an investigation of the primary mechanism of echogenicity. Both components are critical for developing viable clinical applications of ELIP. Mannitol, a cryoprotectant, added during the preparation of ELIP is commonly believed to be critical in making them echogenic. Accordingly, here ELIP prepared with varying amount of mannitol concentration are investigated for their pressure dependent linear and non-linear scattered responses. The average diameter of these liposomes is measured to be 125-185nm. But they have a broad size distribution including liposomes with diameters over a micro-meter as observed by TEM and AFM. These larger liposomes are critical for the overall echogenicity. Attenuation through liposomal solution is measured with four different transducers (central frequencies 2.25, 3.5, 5, 10MHz). Measured attenuation increases linearly with liposome concentration indicating absence of acoustic interactions between liposomes. Due to the broad size distribution, the attenuation shows a flat response without a distinct peak in the range of frequencies (1-12MHz) investigated. A 15-20dB enhancement with 1.67 μg/ml of lipids is observed both for the scattered fundamental and the second harmonic responses at 3.5MHz excitation frequency and 50-800kPa amplitude. It demonstrates the efficacy of ELIP for fundamental as well as harmonic ultrasound imaging. The scattered response however does not show any distinct subharmonic peak for the acoustic excitation parameters studied. Small amount of mannitol proves critical for echogenicity. However, mannitol concentration above 100mM shows no effect.
声敏脂质体（ELIP）是一种很有前途的同时用于成像和药物输送的候选物。它们结合了脂质体的优点——生物相容性和包封疏水性和亲水性药物的能力——以及超声的强反射。本研究的目的是对其进行详细的体外声学特性分析——包括以前未研究过的非线性散射，以及对其声敏性的主要机制进行研究。这两个方面对于开发可行的 ELIP 临床应用都至关重要。甘露醇是一种在制备 ELIP 时添加的冷冻保护剂，通常被认为是使其具有声敏性的关键。因此，在这里研究了具有不同甘露醇浓度的 ELIP 对其压力相关的线性和非线性散射响应。这些脂质体的平均直径测量为 125-185nm。但它们的尺寸分布很宽，包括通过 TEM 和 AFM 观察到的直径超过微米的脂质体。这些较大的脂质体对于整体声敏性至关重要。通过四种不同的换能器（中心频率为 2.25、3.5、5 和 10MHz）测量脂质体溶液的衰减。测量的衰减随脂质体浓度线性增加，表明脂质体之间没有声相互作用。由于尺寸分布较宽，衰减在研究的频率（1-12MHz）范围内没有明显的峰值，呈现出平坦的响应。在 3.5MHz 激励频率和 50-800kPa 幅度下，观察到脂质浓度为 1.67μg/ml 时，基波和二次谐波散射响应分别增强了 15-20dB。这证明了 ELIP 在基波和谐波超声成像中的有效性。然而，在所研究的声激励参数下，散射响应没有显示出任何明显的次谐波峰值。少量的甘露醇对声敏性至关重要。然而，甘露醇浓度高于 100mM 时没有效果。
