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

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

doi:10.1016/j.ultras.2022.106827

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

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

Authors

Bonhye Koo¹, Yunbo Liu², Monica Abboud², Bin Qin³, Yong Wu⁴, Stephanie Choi³, Darby Kozak⁵, Jiwen Zheng⁶

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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. Electronic address: darby.kozak@fda.hhs.gov.
⁶ 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. Electronic address: jiwen.zheng@fda.hhs.gov.

PMID: 36063769
DOI: 10.1016/j.ultras.2022.106827

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.

Keywords: Backscattering coefficient; Coulter counter; Echogenicity; Size distribution; Ultrasound contrast agent.

Publication types

Review

MeSH terms

Contrast Media*
Microbubbles*
Ultrasonography

Substances

Contrast Media