Clustering dynamics of microbubbles exposed to low-pressure 1-MHz ultrasound
File(s)
Author(s)
Lazarus, C
Pouliopoulos, AN
Tinguely, M
Garbin, V
Choi, JJ
Type
Journal Article
Abstract
Ultrasound-driven microbubbles have been used in therapeutic applications to deliver drugs across
capillaries and into cells or to dissolve blood clots. Yet the performance and safety of these applica-
tions have been difficult to control. Microbubbles exposed to ultrasound not only volumetrically
oscillate, but also move due to acoustic radiation, or Bjerknes, forces. The purpose of this work was
to understand the extent to which microbubbles moved and clustered due to secondary Bjerknes
forces. A microbubble population was exposed to a 1-MHz ultrasound pulse with a
peak-rarefactional pressure of 50–100 kPa and a pulse length of 20 ms. Microbubbles exposed to
low-pressure therapeutic ultrasound were observed to cluster at clustering rates of 0.01–0.02 micro-
bubbles per duration (in ms) per initial average inter-bubble distance (in
l
m), resulting in 1 to 3
clustered microbubbles per initial average inter-bubble distance (in
l
m). Higher pressures caused
faster clustering rates and a larger number of clustered microbubbles. Experimental data revealed
clustering time scales, cluster localizations, and cluster sizes that were in reasonable agreement
with simulations using a time-averaged model at low pressures. This study demonstrates that clus-
tering of microbubbles occurs within a few milliseconds and is likely to influence the distribution
of stimuli produced in therapeutic applications.
capillaries and into cells or to dissolve blood clots. Yet the performance and safety of these applica-
tions have been difficult to control. Microbubbles exposed to ultrasound not only volumetrically
oscillate, but also move due to acoustic radiation, or Bjerknes, forces. The purpose of this work was
to understand the extent to which microbubbles moved and clustered due to secondary Bjerknes
forces. A microbubble population was exposed to a 1-MHz ultrasound pulse with a
peak-rarefactional pressure of 50–100 kPa and a pulse length of 20 ms. Microbubbles exposed to
low-pressure therapeutic ultrasound were observed to cluster at clustering rates of 0.01–0.02 micro-
bubbles per duration (in ms) per initial average inter-bubble distance (in
l
m), resulting in 1 to 3
clustered microbubbles per initial average inter-bubble distance (in
l
m). Higher pressures caused
faster clustering rates and a larger number of clustered microbubbles. Experimental data revealed
clustering time scales, cluster localizations, and cluster sizes that were in reasonable agreement
with simulations using a time-averaged model at low pressures. This study demonstrates that clus-
tering of microbubbles occurs within a few milliseconds and is likely to influence the distribution
of stimuli produced in therapeutic applications.
Date Issued
2017-11-20
Date Acceptance
2017-10-21
Citation
Journal of the Acoustical Society of America, 2017, 142 (5), pp.3135-3146
ISSN
0001-4966
Publisher
Acoustical Society of America
Start Page
3135
End Page
3146
Journal / Book Title
Journal of the Acoustical Society of America
Volume
142
Issue
5
Copyright Statement
© 2017 Acoustical Society of America.
Subjects
MD Multidisciplinary
Acoustics
Publication Status
Published