Evaluation of advective solute infiltration to porous media by pulsed focused ultrasound-induced acoustic streaming effects
Jared Van Reet1 , Kate Tunnell1 , Kara Anderson1 , Hyun-Chul Kim2 , Evgenii Kim1 , Kavin Kowsari1 , Seung-Schik Yoo1
1Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
2Department of Artificial Intelligence, Kyungpook National University, Daegu, Korea
Corresponding Author: Seung-Schik Yoo ,Tel: 6177329464, Fax: 6177329185, Email: yoo@bwh.harvard.edu
Received: March 4, 2023;  Accepted: September 9, 2023.  Published online: September 9, 2023.
Acoustic streaming achieved by the application of transcranial focused ultrasound (FUS) promotes localized advective solute transport in the brain and has recently garnered research interest for drug delivery and enhancement of brain waste clearance. The acoustic streaming behavior in brain tissue is difficult to model numerically, thus warrants in vitro examination of effects from using different sonication parameters, in terms of frequency, intensity, and pulse duration (PD).

Melamine and polyvinyl alcohol (PVA) foams were used to mimic the porous brain tissue that contains leptomeningeal fenestrations and perivascular space while agar hydrogel was used to emulate denser neuropil. FUS was delivered to these media, which were immersed in a phosphate buffered saline solution containing toluidine blue O dye, across various frequencies (400, 500, and 600 kHz; applicable to transcranial delivery) in a pulsed mode at two different spatial-peak pulse-average intensities of 3 and 4 W/cm2.

Image analysis showed that the use of 400 kHz yielded the greatest dye infiltration in melamine foam, while sonication did not have any impact on infiltration in the agar hydrogel due to the dominance of diffusional transport. Using a fixed spatial-peak temporal-average intensity of 0.4 W/cm2 at 400 kHz, a PD of 75 ms resulted in the greatest infiltration depth in both melamine and PVA foams among the tested range (50–150 ms).

These findings suggest the existence of a specific frequency and PD that induce greater enhancement of solute/fluid movement for its ultimate in vivo application in promoting waste clearance from the brain.
Keywords: Radiation Force; Bulk flow; Phantom; Alzheimer’s disease; Glymphatic
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