In vivo high-speed microscopy of microbubbles in the chorioallantoic membrane model
Rojin Anbarafshan1,2, Carly Pellow2, Kevin Kiezun2
1Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7, Canada.
Theranostics
|March 20, 2024
Summary
High-pressure focused ultrasound causes microbubbles to extravasate from microvessels, leading to red blood cell leakage. This study provides the first in vivo evidence linking microbubble extravasation to microvessel rupture during ultrasound therapy.
Area of Science:
- Biomedical Engineering
- Ultrasound Therapeutics
- Microvascular Physiology
Background:
- Acoustic stimulation of microbubbles induces bioeffects like permeabilization and perfusion shutdown.
- Microbubble-microvessel interactions are poorly understood at high pressures due to limited in vivo data.
- Linking microbubble-microvessel interactions, cavitation, and bioeffects is crucial for focused ultrasound development.
Purpose of the Study:
- To investigate high-pressure focused ultrasound-induced microbubble-microvessel interactions in vivo.
- To establish the link between microbubble extravasation and microvascular damage.
- To provide direct in vivo observations of these phenomena.
Main Methods:
- Developed a system for simultaneous high-speed intravital imaging and cavitation monitoring.
- Used Definity™ microbubbles in a chorioallantoic membrane model.
- Conducted exposures at 1 MHz, 0.5-3.5 MPa, with 5 ms pulse length.
Main Results:
- Ultrasound-activated microbubbles induced localized microvessel wall deformations, increasing with pressure.
- Microbubble extravasation occurred in 34-79% of vessels and increased with pressure, affecting larger vessels.
- Red blood cell leakage followed microbubble extravasation in 96% of cases at pressures ≥1 MPa.
Conclusions:
- This is the first high-speed in vivo study of high-pressure focused ultrasound and microbubble-microvessel interactions.
- Direct evidence shows activated microbubble extravasation occurs in vivo.
- Microbubble extravasation is linked to microvessel wall perforations causing red blood cell leakage, explaining microvessel rupture.
