Biomedical Engineering Program, University of Colorado, Boulder, Colorado 80309, United States.
Mechanical Engineering Department, University of Colorado, Boulder, Colorado 80309, United States.
Bioconjug Chem. 2022 Jun 15;33(6):1106-1113. doi: 10.1021/acs.bioconjchem.2c00155. Epub 2022 Apr 27.
Microbubbles (1-10 μm diameter) have been used as conventional ultrasound contrast agents (UCAs) for applications in contrast-enhanced ultrasound (CEUS) imaging. Nanobubbles (<1 μm diameter) have recently been proposed as potential extravascular UCAs that can extravasate from the leaky vasculature of tumors or sites of inflammation. However, the echogenicity of nanobubbles for CEUS remains controversial owing to prior studies that have shown very low ultrasound backscatter. We hypothesize that microbubble contamination in nanobubble formulations may explain the discrepancy. To test our hypothesis, we examined the size distributions of lipid-coated nanobubble and microbubble suspensions using multiple sizing techniques, examined their echogenicity in an agar phantom with fundamental-mode CEUS at 7 MHz and 330 kPa peak negative pressure, and interpreted our results with simulations of the modified Rayleigh-Plesset model. We found that nanobubble formulations contained a small contamination of microbubbles. Once the contribution from these microbubbles is removed from the acoustic backscatter, the acoustic contrast of the nanobubbles was shown to be near noise levels. This result indicates that nanobubbles have limited utility as UCAs for CEUS.
微泡（直径 1-10μm）一直被用作传统超声造影剂（UCAs），用于对比增强超声（CEUS）成像。纳米泡（直径<1μm）最近被提议作为潜在的血管外 UCAs，能够从肿瘤或炎症部位的渗漏血管中外渗。然而，由于先前的研究表明纳米泡的超声背散射非常低，因此纳米泡用于 CEUS 的声振性仍然存在争议。我们假设纳米泡制剂中的微泡污染可能解释了这种差异。为了验证我们的假设，我们使用多种粒径测定技术检查了脂质包覆的纳米泡和微泡悬浮液的粒径分布，在 7MHz 和 330kPa 峰值负压的琼脂体模中用基本模式 CEUS 检查了它们的声振性，并通过修正的瑞利-普莱塞特模型模拟解释了我们的结果。我们发现纳米泡制剂中含有少量微泡。一旦从声背散射中去除这些微泡的贡献，纳米泡的声对比就接近噪声水平。这一结果表明，纳米泡作为 CEUS 的 UCAs 的应用有限。
