表征尺寸分布和浓度如何影响超声造影剂的回声性。

Characterizing how size distribution and concentration affect echogenicity of ultrasound contrast agents.

作者信息

Koo Bonhye, Liu Yunbo, Abboud Monica, Qin Bin, Wu Yong, Choi Stephanie, Kozak Darby, Zheng Jiwen

机构信息

Division of Therapeutic Performance, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, United States; Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, United States.

Division of Applied Mechanics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, United States.

出版信息

Ultrasonics. 2023 Jan;127:106827. doi: 10.1016/j.ultras.2022.106827. Epub 2022 Aug 27.

DOI:10.1016/j.ultras.2022.106827

PMID:36063769

Abstract

We investigated the effects of UCA gas bubble size distribution and concentration on the generated ultrasound echogenicity signal. Gas bubble size characterization using Coulter Counter and cryogenic-SEM revealed the hollow structure and rare presence of microbubbles >10 µm in a commercial UCA product, Lumason™. Volume-weighed size and concentration were observed to be more sensitive to changes in UCA bubble stability than number-weighted size and concentration. Size distribution measurements showed that the force (e.g., shaking/agitation energy) used to redisperse the sample did not affect the size distribution, concentration, or echogenicity of the UCA sample. The ultrasound backscattering coefficient (BSC) of size fractionated and serial diluted microbubbles showed that the echogenicity signal correlates most with UCA bubble concentration, especially volume-weighted concentration. Findings from this study may be used to support demonstrating the equivalence of a generic UCA product to the reference listed drug.

摘要

我们研究了超声造影剂（UCA）气泡大小分布和浓度对所产生的超声回声信号的影响。使用库尔特计数器和低温扫描电子显微镜对气泡大小进行表征，结果显示在一款商用UCA产品Lumason™中存在中空结构，且极少有大于10微米的微泡。观察发现，体积加权大小和浓度比数量加权大小和浓度对UCA气泡稳定性变化更敏感。大小分布测量表明，用于重新分散样品的力（如摇晃/搅拌能量）不会影响UCA样品的大小分布、浓度或回声性。对按大小分级和系列稀释的微泡的超声背向散射系数（BSC）研究表明，回声信号与UCA气泡浓度（尤其是体积加权浓度）的相关性最强。本研究结果可用于支持证明一种通用UCA产品与参比上市药品的等效性。