Pitt Shield

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

We are open to feedback. If you see a mistake or have a suggestion, please contact us.

← Back to Search