High-speed imaging of microsphere transport by cavitation activity in a tissue-mimicking phantom

Journal article

Objective
Ultrasound-mediated cavitation has been harnessed to improve the delivery of various therapeutics, including the extravasation of small molecule drugs and nanoparticles (<1 µm) into soft tissue. This study investigated whether cavitation could also enhance the extravasation of larger (>10 µm) therapeutic particles, representative of radio- or chemo-embolic particles, in a tissue-mimicking phantom.

Methods
High-speed (10³–10⁶ frames/s) optical imaging was used to observe the motion of glass microspheres with diameters of 15–32 or 105–107 µm in an agar phantom under exposure to high-intensity focused ultrasound (0.5 MHz) at a range of peak negative pressures (1.9–2.8 MPa) in the presence of SonoVue microbubbles.

Results
In contrast to the microstreaming reported to be responsible for nanoparticle transport, the formation and translation of bubble clouds were found to be primarily responsible for the motion of glass microspheres. The bubble clouds were seen both to create channels in the phantom and to travel along them under the action of primary acoustic radiation force, either propelling or entraining microspheres with them. Collisions between microspheres were also seen to promote cloud formation and cavitation activity.

Conclusion
Ultrasound-mediated cavitation can promote the transport of solid microparticles in tissue-mimicking material. Further work is needed to understand the influence of tissue mechanical properties and ultrasound exposure parameters on the extent and uniformity of particle distribution that can be achieved.

Authors: Vince, J; Lewis, A; Stride, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Ultrasound in Medicine and Biology
• Volume: 49
• Issue: 6
• Pages: 1415-1421
• Publication date: 2023-03-15
• Acceptance date: 2023-01-30
• DOI: 10.1016/j.ultrasmedbio.2023.01.025
• EISSN: 1879-291X
• ISSN: 0301-5629
• Language: English
• Keywords: Extravasation; Therapeutic ultrasound; Embolic microspheres; FFR; High-speed imaging; Cavitation