Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Ultrasound Med Biol. 2013 May;39(5):882-92. doi: 10.1016/j.ultrasmedbio.2013.01.006. Epub 2013 Mar 1.
Lipid-coated bubbles exhibit oscillation responses capable of enhancing the sensitivity of ultrasound imaging by improving contrast. Further improvements in performance enhancement require control of the size distribution of bubbles to promote correspondence between their resonance frequency and the frequency of the ultrasound. Here we describe a size-controlling technique that can shift the size distribution using a currently available agitation method. This technique is based on regulating the membrane dynamic fluidity of lipid mixtures and provides a general size-controlling variable that could also be applied in other fabrication methods. Three materials (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine, 1,2-dioctadecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) and polyethylene glycol 40 stearate) with distinct initial fluidities and phase behaviors were used to demonstrate the use of fluidity regulation to control bubble sizes. Bubble size distributions of different formulations were determined by electrical impedance sensing, and bubble volumes and surface areas were calculated. To confirm the relationship between regulated fluidity and mean bubble size, the membrane fluidity of each composition was determined by fluorescence anisotropy, with the results indicating linear relations in the compositions with similar main transition temperatures. Compositions with a higher molar proportion of polyethylene glycol 40 stearate showed higher fluidities and larger bubbles. B-mode ultrasound imaging was performed to investigate the echogenicity and lifetime of the fabricated bubbles, with the results indicating that co-mixing a high-transition-temperature charged lipid (i.e., 1,2-dioctadecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) extends the tailoring range of this fluidity regulation technique, allowing refined and continuous changes in mean bubble size (from 0.93 to 2.86 μm in steps of ∼0.5 μm), and also prolongs bubble lifetime. The polydispersity of each composition was also determined to evaluate practicality in particular applications. Our study demonstrates a feasible approach to naturally controling bubble size distribution and provides a practical reference for other fabrication systems and ultrasound imaging applications.
脂质气泡表现出的振荡响应能够通过提高对比度来增强超声成像的灵敏度。进一步提高性能增强需要控制气泡的大小分布，以促进其共振频率与超声频率之间的对应关系。在这里，我们描述了一种使用现有搅拌方法可以改变大小分布的控制技术。该技术基于调节脂质混合物的膜动态流变性，并提供了一种通用的大小控制变量，也可应用于其他制造方法。我们使用三种具有不同初始流变性和相行为的材料（1,2-二硬脂酰基-sn-甘油-3-磷酸胆碱、1,2-二油酰基-sn-甘油-3-磷酸-(1'-rac-甘油)和聚乙二醇 40 硬脂酸酯）来演示使用流变性调节来控制气泡大小。通过电阻抗感应测定不同配方的气泡大小分布，并计算气泡体积和表面积。为了确认调节流变性与平均气泡大小之间的关系，通过荧光各向异性测定了每种组成的膜流变性，结果表明在具有相似主相变温度的组成中呈线性关系。具有较高摩尔比例的聚乙二醇 40 硬脂酸酯的组成表现出较高的流变性和较大的气泡。进行 B 模式超声成像以研究所制备气泡的回声和寿命，结果表明共混高相变温度带电脂质（即 1,2-二油酰基-sn-甘油-3-磷酸-(1'-rac-甘油））扩展了该流变性调节技术的调整范围，允许平均气泡大小进行精细和连续的变化（从 0.93 至 2.86μm，步长约为 0.5μm），并延长了气泡寿命。还测定了每种组成的多分散性，以评估其在特定应用中的实用性。我们的研究证明了一种可行的方法来自然控制气泡大小分布，并为其他制造系统和超声成像应用提供了实用参考。
