IEEE Trans Ultrason Ferroelectr Freq Control. 2018 Aug;65(8):1389-1401. doi: 10.1109/TUFFC.2018.2841848. Epub 2018 May 29.
In this paper, we assess the importance of microbubble shell composition for contrast-enhanced imaging sequences commonly used on clinical scanners. While the gas core dynamics are primarily responsible for the nonlinear harmonic response of microbubbles at diagnostic pressures, it is now understood that the shell rheology plays a dominant role in the nonlinear response of microbubbles subjected to low acoustic pressures. Of particular interest here, acoustic pressures of tens of kilopascal can cause a reversible phase transition of the phospholipid coatings from a stiff elastic organized state to a less stiff disorganized buckled state. Such a transition from elastic to buckled shell induces a steep variation of the shell elasticity, which alters the microbubble acoustic scattering properties. We demonstrate in this paper that this mechanism plays a dominant role in contrast pulse sequences that modulate the amplitude of the insonifying pulse pressure. The contrast-to-tissue ratio (CTR) for amplitude modulation (AM), pulse inversion (PI), and amplitude modulation pulse inversion (AMPI) is measured in vitro for Definity, Sonazoid, both lipid-encapsulted microbubbles, and the albumin-coated Optison. It is found that pulse sequences using AM significantly enhanced the nonlinear response of all studied microbubbles compared to PI (up to 15 dB more) when low insonation pressures under 200 kPa were used. Further investigation reveals that the origin of the hyperechoicity is a small phase lag occurring between the echoes from the full-and half-amplitude driving pulses, and that the effect could be attributed to the shell softening dynamics of lipid and albumin coatings. We assess that this additional phase in microbubble ultrasound scattering can have a dominant role in the CTR achieved in contrast sequences using AM. We also show that the pressure dependent phase lag is a specific marker for microbubbles with no equivalent in tissue, which can be used to segment microbubbles from the tissue harmonics and significantly increase the CTR.
在本文中，我们评估了微泡壳组成对于临床扫描仪上常用的对比增强成像序列的重要性。虽然在诊断压力下，气泡核动力学主要负责微泡的非线性谐波响应，但现在已经了解到，壳流变学在低声压下的微泡非线性响应中起主导作用。在这里特别感兴趣的是，数十千帕斯卡的声压可导致磷脂涂层从刚性弹性组织状态到较少刚性的无序褶皱状态的可逆相转变。这种从弹性到褶皱壳的转变引起壳弹性的急剧变化，从而改变微泡的声散射特性。本文证明，这种机制在调制激励脉冲压力幅度的对比脉冲序列中起主导作用。在体外测量 Definity、Sonazoid（两种脂质包封的微泡）和白蛋白包被的 Optison 的幅度调制（AM）、脉冲反转（PI）和幅度调制脉冲反转（AMPI）的对比组织比（CTR）。发现当使用低于 200 kPa 的低致声压力时，与 PI 相比（高达 15 dB），使用 AM 的脉冲序列显著增强了所有研究微泡的非线性响应。进一步的研究表明，超回声的起源是来自全幅和半幅驱动脉冲的回波之间发生的小相位滞后，并且该效应可归因于脂质和白蛋白涂层的壳软化动力学。我们评估认为，这种微泡超声散射中的附加相位可能在使用 AM 的对比序列中实现的 CTR 中起主导作用。我们还表明，压力相关的相位滞后是无等效组织的微泡的特定标记，可用于将微泡与组织谐波分开，并显著提高 CTR。
