Department of Electrical and Computer Engineering, University of Rochester, Rochester, New York 14627, USA.
Med Phys. 2013 Aug;40(8):082903. doi: 10.1118/1.4813017.
Subharmonic imaging is of interest for high frequency (>10 MHz) nonlinear imaging, because it can specifically detect the response of ultrasound contrast agents (UCA). However, conventional UCA produce a weak subharmonic response at high frequencies, which limits the sensitivity of subharmonic imaging. We hypothesized that modifying the size distribution of the agent can enhance its high-frequency subharmonic response. The overall goal of this study was to investigate size-manipulated populations of the agent to determine the range of sizes that produce the strongest subharmonic response at high frequencies (in this case, 20 MHz). A secondary goal was to assess whether the number or the volume-weighted size distribution better represents the efficacy of the agent for high-frequency subharmonic imaging.
The authors created six distinct agent size distributions from the native distribution of a commercially available UCA (Targestar-P®). The median (number-weighted) diameter of the native agent was 1.63 μm, while the median diameters of the size-manipulated populations ranged from 1.35 to 2.99 μm. The authors conducted acoustic measurements with native and size-manipulated agent populations to assess their subharmonic response to 20 MHz excitation (pulse duration 1.5 μs, pressure amplitudes 100-398 kPa).
The results showed a considerable difference between the subharmonic response of the agent populations that were investigated. The subharmonic response peaked for the agent population with a median diameter of 2.15 μm, which demonstrated a subharmonic signal that was 8 dB higher than the native agent. Comparing the subharmonic response of different UCA populations indicated that microbubbles with diameters between 1.3 and 3 μm are the dominant contributors to the subharmonic response at 20 MHz. Additionally, a better correlation was observed between the subharmonic response of the agent and the number-weighted size-distribution (R2=0.98) than with the volume-weighted size distribution (R2=0.53).
Modifying the size distribution of the agent appears to be a viable strategy to improve the sensitivity of high-frequency subharmonic imaging. In addition, when the size distribution of the UCA has not been suitably modified, the number-weighted size distribution is a useful parameter to accurately describe the efficacy of the agent for high-frequency subharmonic imaging.
次谐波成像是高频（>10MHz）非线性成像的研究热点，因为它可以特异性地探测超声造影剂（UCA）的反应。然而，传统的 UCA 在高频时产生较弱的次谐波反应，这限制了次谐波成像的灵敏度。我们假设改变造影剂的大小分布可以增强其高频次谐波反应。本研究的总体目标是研究经过大小处理的造影剂群体，以确定在高频（在此情况下为 20MHz）下产生最强次谐波反应的大小范围。次要目标是评估数量加权或体积加权大小分布是否更好地代表造影剂用于高频次谐波成像的效果。
作者从市售 UCA（Targestar-P®）的天然分布中创建了六个不同的造影剂大小分布。天然造影剂的中值（数量加权）直径为 1.63μm，而经过大小处理的群体的中值直径范围为 1.35μm 至 2.99μm。作者对天然和大小处理的造影剂群体进行了声学测量，以评估它们对 20MHz 激励的次谐波反应（脉冲持续时间 1.5μs，压力幅度 100-398kPa）。
结果显示，研究中的造影剂群体的次谐波反应存在显著差异。中值直径为 2.15μm 的造影剂群体的次谐波反应达到峰值，其次谐波信号比天然造影剂高 8dB。比较不同 UCA 群体的次谐波反应表明，直径在 1.3μm 至 3μm 之间的微泡是 20MHz 下次谐波反应的主要贡献者。此外，与体积加权大小分布（R2=0.53）相比，造影剂的次谐波反应与数量加权大小分布（R2=0.98）之间的相关性更好。
改变造影剂的大小分布似乎是提高高频次谐波成像灵敏度的可行策略。此外，当 UCA 的大小分布未得到适当修改时，数量加权大小分布是准确描述造影剂用于高频次谐波成像效果的有用参数。
