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Published on: June 12, 2021
Influences of microbubble diameter and ultrasonic parameters on in vitro sonothrombolysis efficacy
Michael J Borrelli1, William D O'Brien, Eric Hamilton
1Department of Radiology, University of Arkansas for Medical Sciences, 4301 West Markham Street Slot #556, Little Rock, AR 72205, USA. mjborrelli@uams.edu
Purpose:
To quantify the effects of microbubble (MB) size, elasticity, and pulsed ultrasonic parameters on in vitro sonothrombolysis (ultrasound [US]-mediated thrombolysis) efficacy.
Materials And Methods:
Monodispersive MBs with diameters of 1 μm or 3 μm were exposed to pulsed US (1 MHz or 3 MHz) to lyse rabbit blood clots. Sonothrombolysis efficacy (clot mass loss) was measured as functions of MB size and concentration, ultrasonic frequency and intensity, pulse duration (PD), pulse repeat frequency (PRF), and duty factor.
Results:
Sonothrombolysis at 1 MHz was more effective using 3-μm MBs and at 3 MHz using 1-μm MBs. Sonothrombolysis was more effective at 1 MHz when≥75% of MBs remained intact, especially for 3-μm MBs; improving sonothrombolysis by increasing PRF from 100 Hz to 400 Hz at 3 MHz was associated with increasing 3-μm MB survival. However, 60% of 1-μm MBs were destroyed during maximal sonothrombolysis at 3 MHz, indicating that considerable MB collapse may be required for sonothrombolysis under these conditions.
Conclusions:
The ability to control MB size and elasticity permits using a wide range of US parameters (eg, frequency, intensity) to produce desired levels of sonothrombolysis. Comparable, maximal sonothrombolysis efficacy was achieved at 20-fold lower intensity with 3-μm MBs (0.1W/cm(2)) than with 1-μm MBs (2.0W/cm(2)), a potential safety issue for in vivo sonothrombolysis. US parameters that maximized MB survival yielded maximal sonothrombolysis efficacy except with 1-μm MBs at 3MHz where most MBs were destroyed.
Insights
Microbubble size and ultrasound parameters significantly impact sonothrombolysis efficacy. Optimal results depend on matching microbubble size to ultrasound frequency for effective clot lysis.
Area of Science:
- Biomedical Engineering
- Acoustic Medicine
- Thrombosis Research
Background:
- Sonothrombolysis utilizes ultrasound to enhance clot dissolution.
- Microbubbles (MBs) are crucial agents in ultrasound-mediated thrombolysis.
- Optimizing MB properties and ultrasound parameters is key for therapeutic efficacy.
Purpose of the Study:
- To quantify the effects of microbubble size, elasticity, and pulsed ultrasonic parameters on in vitro sonothrombolysis efficacy.
- To determine the relationship between microbubble characteristics and ultrasound settings for optimal clot lysis.
- To investigate potential safety implications of varying parameters for in vivo applications.
Main Methods:
- Monodisperse microbubbles (1 μm and 3 μm) were used to lyse rabbit blood clots.
- Pulsed ultrasound at 1 MHz and 3 MHz was applied.
- Sonothrombolysis efficacy was measured based on clot mass loss, varying microbubble size, concentration, ultrasound frequency, intensity, pulse duration, pulse repeat frequency, and duty cycle.
Main Results:
- Sonothrombolysis was more effective with 3-μm MBs at 1 MHz and 1-μm MBs at 3 MHz.
- Maximal efficacy was achieved when microbubbles largely remained intact, particularly 3-μm MBs at 1 MHz.
- Significant microbubble destruction was observed with 1-μm MBs at 3 MHz, suggesting a role for microbubble collapse in lysis.
Conclusions:
- Microbubble size and elasticity can be tailored to optimize ultrasound parameters for sonothrombolysis.
- Comparable maximal sonothrombolysis was achieved with significantly lower ultrasound intensity using 3-μm MBs compared to 1-μm MBs.
- Ultrasound parameters maximizing microbubble survival generally yielded maximal sonothrombolysis, with exceptions noted for 1-μm MBs at 3 MHz.
