High-intensity focused ultrasound sonothrombolysis: the use of perfluorocarbon droplets to achieve clot lysis at reduced acoustic power.
Authors: Pajek D, Burgess A, Huang Y, Hynynen K
The purpose of this study was to evaluate use of intravascular perfluorocarbon droplets to reduce the sonication power required to achieve clot lysis with high-intensity focused ultrasound. High-intensity focused ultrasound with droplets was initially applied to blood clots in an in vitro flow apparatus, and inertial cavitation thresholds were determined. An embolic model for ischemic stroke was used to illustrate the feasibility of this technique in vivo. Recanalization with intravascular droplets was achieved in vivo at 24 ± 5% of the sonication power without droplets. Recanalization occurred in 71% of rabbits that received 1-ms pulsed sonications during continuous intravascular droplet infusion (p = 0.041 vs controls). Preliminary experiments indicated that damage was confined to the ultrasonic focus, suggesting that tolerable treatments would be possible with a more tightly focused hemispheric array that allows the whole focus to be placed inside of the main arteries in the human brain.
Introduction
Purpose
drug delivery with BBB opening
Study Objective
Evaluate whether intravascular perfluorocarbon droplets reduce the acoustic power needed for HIFU-mediated clot lysis via inertial cavitation
Animal model / Human subject
New Zealand White Rabbits, male
Disease model
embolic model of acute ischemic stroke (AIS)
MRI or image guidance method
Yes (MRI)
Targeted brain region(s)
Middle Cerebral Artery (Mca)
Cargo name and characteristics
perfluorocarbon droplets (dodecafluoropentane, DDFP)
Route of administration
intra-arterial
Outcomes and Safety
Summary of Outcomes
Droplets reduced inertial cavitation threshold to 49±9 W in vitro. In vivo, 1 ms pulsed sonication with continuous droplet infusion achieved 71% recanalization (p=0.041) at 24±5% of the power required without droplets. Recanalization was confirmed by angiography.
Safety-related matter
Micro-extravasations (red blood cells) observed in all treated groups. Blood pooling occurred when focus was placed near skull (2/2 cases). No major vessel damage on angiography.
Brain Region
Ultrasound Parameters
Ultrasound instrument
In-house spherically focused HIFU transducer (10 cm diameter, 10 cm radius of curvature)
FUS Frequency
1.513MHz
FUS Pressure
5.8 +- 0.5MPa
FUS Mode
pulsed
Pulse duration
1ms
Duration of a single FUS session
20s
Focal Characteristics
transducer produced a -6dB focus of 0.9 mm × 7.1 mm
Treatment frequency
single session
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