Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Ultrasound Med Biol. 2012 May;38(5):846-63. doi: 10.1016/j.ultrasmedbio.2012.01.011. Epub 2012 Mar 6.
There are a range of contrast ultrasound applications above 10 MHz, a frequency regime in which nonlinear microbubble behavior is poorly understood. Lipid-encapsulated microbubbles have considerable potential for use at higher frequencies because they have been shown to exhibit pronounced nonlinear activity at frequencies up to 40 MHz. The objective of this work was to investigate the influence of agent formulation on the subharmonic response of lipid-encapsulated microbubbles at high frequencies with a view to providing information relevant to improving contrast agent design and imaging performance. An optical-acoustical setup was used to measure the subharmonic emissions from small (d < 3 μm) individual lipid-encapsulated microbubbles as a function of transmit pressure, size and composition. In this study, five agent formulations (Definity™, MicroMarker™ and three in-house agents manipulated to exhibit different levels of shell microstructure heterogeneity) were insonified at 25 MHz over a peak negative pressure (P(n)) range of 0.02-1.2 MPa. All agents exhibited distinctly different subharmonic behavior, both in terms of amplitude and active sizes. MicroMarker™ exhibited the strongest, broadest and most consistent subharmonic response, 22% greater in power than that of Definity™ and as much as 50% greater than the in-house formulations. No clear relation between in-house agents' shell microstructure and nonlinear response was found, other than the variability in the nonlinear response itself. An analysis of the response of MicroMarker™ bubbles suggests that these bubbles exhibit "expansion-dominated" oscillations, in contrast to "compression-only" oscillations observed for similar bubbles at lower frequencies (f < 11 MHz).
在 10MHz 以上的频率范围内，存在多种对比超声应用，而在这个频率范围内，非线性微泡行为还没有被很好地理解。脂质包裹的微泡在更高的频率下具有很大的应用潜力，因为它们已经被证明在高达 40MHz 的频率下表现出明显的非线性活动。这项工作的目的是研究制剂配方对高频下脂质包裹微泡的次谐波响应的影响，以期为改进造影剂设计和成像性能提供相关信息。采用光声装置测量了小（d<3μm）单个脂质包裹微泡的次谐波发射，作为传输压力、尺寸和组成的函数。在这项研究中，五种制剂配方（DefinityTM、MicroMarkerTM和三种为了表现出不同程度的壳层微观结构异质性而人为处理的内部制剂）在 25MHz 下被超声照射，峰值负压（P(n)）范围为 0.02-1.2MPa。所有制剂都表现出明显不同的次谐波行为，无论是在幅度还是在有效尺寸方面。MicroMarkerTM表现出最强、最宽和最一致的次谐波响应，功率比 DefinityTM高 22%，比内部制剂高 50%。除了非线性响应本身的可变性外，没有发现内部制剂的壳层微观结构和非线性响应之间有明显的关系。对 MicroMarkerTM微泡响应的分析表明，这些微泡表现出“扩张主导”的振荡，与在较低频率（f<11MHz）下观察到的类似微泡的“仅压缩”振荡形成对比。
