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Multi-timescale Microscopy Methods for the Characterization of Fluorescently-labeled Microbubbles for Ultrasound-Triggered Drug Release
Published on: June 12, 2021
Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells
Kyosuke Yanagisawa1, Fuminori Moriyasu, Takeo Miyahara
1Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Abstract:
Delayed parenchymal phase images of the liver more than 5 min after IV injection of ultrasound contrast agents are thought to be related to the phagocytosis of contrast agent microbubbles by macrophages. In this study, we examined whether liver-specific macrophages, Kupffer cells, phagocytosed the microbubbles and whether their elimination affected the delayed parenchymal images of the liver. Phase-contrast microscope observations showed that Kupffer cells phagocytosed various contrast agents in vitro. Among the contrast agents used, 99% of Sonazoid and Optison, and 47% of Levovist were phagocytosed, whereas only 7.3% of SonoVue and 0% of Imavist were phagocytosed. Elimination of Kupffer cells in vivo by gadolinium chloride (GdCl(3)) resulted in decreased intensity of the delayed parenchymal images with Sonazoid and Levovist, while SonoVue showed no changes compared with control. Our findings suggested that Kupffer cells phagocytosed contrast agents and they were responsible for the delayed images of contrast ultrasound in the liver.
Insights
Kupffer cells, the liver's macrophages, engulf ultrasound contrast agent microbubbles. This phagocytosis is responsible for the delayed parenchymal liver images seen in contrast-enhanced ultrasound.
Area of Science:
- Hepatology
- Radiology
- Immunology
Background:
- Delayed parenchymal phase liver images in ultrasound contrast imaging are linked to macrophage phagocytosis of microbubbles.
- The specific role of liver-resident macrophages (Kupffer cells) in this process remains to be fully elucidated.
Purpose of the Study:
- To investigate whether Kupffer cells phagocytose ultrasound contrast agents.
- To determine if Kupffer cell elimination impacts delayed liver parenchymal phase imaging.
Main Methods:
- In vitro phase-contrast microscopy to observe Kupffer cell phagocytosis of various ultrasound contrast agents.
- In vivo Kupffer cell depletion using gadolinium chloride (GdCl(3)).
- Assessment of delayed liver parenchymal phase imaging intensity following contrast agent administration in control and Kupffer cell-depleted mice.
Main Results:
- Kupffer cells demonstrated in vitro phagocytosis of Sonazoid, Optison, Levovist, and SonoVue, with varying efficiencies (99% for Sonazoid/Optison, 47% for Levovist, 7.3% for SonoVue).
- In vivo Kupffer cell elimination led to reduced delayed parenchymal image intensity with Sonazoid and Levovist.
- No significant changes in delayed imaging were observed with SonoVue after Kupffer cell depletion.
Conclusions:
- Kupffer cells actively phagocytose ultrasound contrast agents.
- Kupffer cell phagocytosis is a key mechanism responsible for the delayed parenchymal phase liver images in contrast-enhanced ultrasound.
- The degree of Kupffer cell involvement varies depending on the specific ultrasound contrast agent used.
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