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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
In vivo imaging of microfluidic-produced microbubbles
Ali H Dhanaliwala1, Adam J Dixon, Dan Lin
1Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
In situ microfluidic production of microbubbles in mouse vasculature offers a novel approach for ultrasound contrast enhancement. This method bypasses the need for high production rates and long stability, demonstrating feasibility in vivo.
Area of Science:
- Biomedical Engineering
- Medical Imaging
- Nanotechnology
Background:
- Microfluidics enables precise microbubble production for medical applications like ultrasound contrast.
- Current methods face limitations in production rate, stability, and diameter control.
- In situ vascular production could overcome these limitations.
Purpose of the Study:
- To investigate the feasibility of in situ microfluidic microbubble production directly within the vasculature.
- To assess the ultrasound contrast enhancement capabilities of these microbubbles in vivo.
- To evaluate the safety and physiological impact of direct vascular administration.
Main Methods:
- Microfluidic device used to generate nitrogen gas microbubbles stabilized with bovine serum albumin and dextrose.
- Microbubbles injected intravenously into wild-type C57BL/6 mice via tail-vein catheter.
- Ultrasound imaging (12.5 MHz) of cardiac ventricles to analyze microbubble transit and image intensity over time.
Main Results:
- Microbubbles produced at rates of approximately 10^5 bubbles/s were observed in both right and left ventricles.
- Median transit times in the right ventricle: 2.9s (rise), 21.3s (duration), 14.3s (decay).
- Mice tolerated the procedure well, with no observable respiratory or cardiac distress, even with microbubbles up to 19 μm.
Conclusions:
- In situ microfluidic microbubble generation in the vasculature is feasible for ultrasound contrast.
- This approach demonstrates potential for simplified in vivo contrast agent administration.
- The method shows promise for applications in diagnostic imaging and potentially drug/gene delivery.
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