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Updated: May 5, 2026

Imaging and Quantification of the Area of Fast-Moving Microbubbles Using a High-Speed Camera and Image Analysis
Published on: September 5, 2020
Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles
J R Lindner1, P A Dayton, M P Coggins
1Cardiovascular Division, University of Virginia School of Medicine, Charlottesville, USA. jlindner@virginia.edu
Background:
We have previously shown that microbubbles adhere to leukocytes in regions of inflammation. We hypothesized that these microbubbles are phagocytosed by neutrophils and monocytes and remain acoustically active, permitting their detection in inflamed tissue.
Methods And Results:
In vitro studies were performed in which activated leukocytes were incubated with albumin or lipid microbubbles and observed under microscopy. Microbubbles attached to the surface of activated neutrophils and monocytes, were phagocytosed, and remained intact for up to 30 minutes. The rate of destruction of the phagocytosed microbubbles on exposure to ultrasound was less (P=0.05) than that of free microbubbles at all acoustic pressures applied. Intravital microscopy and simultaneous ultrasound imaging of the cremaster muscle was performed in 6 mice to determine whether phagocytosed microbubbles could be detected in vivo. Fifteen minutes after intravenous injection of fluorescein-labeled microbubbles, when the blood-pool concentration was negligible, the number of phagocytosed/attached microbubbles within venules was 7-fold greater in tumor necrosis factor-alpha (TNF-alpha)-treated animals than in control animals (P<0.01). This increase in retained microbubbles resulted in a 5- to 6-fold-greater (P<0.01) degree of ultrasound contrast enhancement than in controls.
Conclusions:
After attaching to activated neutrophils and monocytes, microbubbles are phagocytosed intact. Despite viscoelastic damping, phagocytosed microbubbles remain responsive to ultrasound and can be detected by ultrasound in vivo after clearance of freely circulating microbubbles from the blood pool. Thus, contrast ultrasound has potential for imaging sites of inflammation.
Insights
Microbubbles are phagocytosed by immune cells at inflammation sites and remain detectable by ultrasound. This contrast-enhanced ultrasound technique shows promise for imaging inflammatory tissues.
Area of Science:
- Biomedical Engineering
- Diagnostic Imaging
- Immunology
Background:
- Microbubbles previously shown to adhere to leukocytes in inflamed areas.
- Hypothesis: Microbubbles are phagocytosed by neutrophils and monocytes, remaining acoustically active for detection.
Purpose of the Study:
- To investigate if phagocytosed microbubbles remain acoustically active and detectable in vivo.
- To assess the potential of contrast-enhanced ultrasound for imaging inflammation.
Main Methods:
- In vitro studies: activated leukocytes incubated with microbubbles, observed via microscopy.
- In vivo studies: intravital microscopy and ultrasound imaging in mice after microbubble injection.
- Assessed microbubble attachment, phagocytosis, acoustic activity, and ultrasound contrast enhancement.
Main Results:
- Microbubbles were phagocytosed by neutrophils and monocytes, remaining intact for up to 30 minutes.
- Phagocytosed microbubbles showed reduced destruction under ultrasound compared to free microbubbles.
- In vivo, inflamed tissues had 7-fold more phagocytosed microbubbles and 5-6 fold greater ultrasound contrast enhancement.
Conclusions:
- Phagocytosed microbubbles remain intact and acoustically responsive.
- Contrast-enhanced ultrasound can detect phagocytosed microbubbles in vivo after circulating microbubbles clear.
- This technique holds potential for imaging inflammatory sites.
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