Creating brain lesions with low-intensity focused ultrasound with microbubbles: a rat study at half a megahertz.
Authors: Huang Y, Vykhodtseva NI, Hynynen K
Low-intensity focused ultrasound was applied with microbubbles (Definity, Lantheus Medical Imaging, North Billerica, MA, USA; 0.02 mL/kg) to produce brain lesions in 50 rats at 558 kHz. Burst sonications (burst length: 10 ms; pulse repetition frequency: 1 Hz; total exposure: 5 min; acoustic power: 0.47-1.3 W) generated ischemic or hemorrhagic lesions at the focal volume revealed by both magnetic resonance imaging and histology. Shorter burst time (2 ms) or shorter sonication time (1 min) reduced the probability of lesion production. Longer pulses (200 ms, 500 ms and continuous wave) caused significant near-field damage. Using microbubbles with focused ultrasound significantly reduced acoustic power levels and, therefore, avoided skull heating issues and potentially can extend the treatable volume of transcranial focused ultrasound to brain tissues close to the skull.
Introduction
Purpose
Thermal ablation
Study Objective
To evaluate whether low-intensity focused ultrasound combined with microbubbles can produce brain lesions in rats at reduced acoustic power and to determine how sonication parameters affect lesion formation.
Animal model / Human subject
Rat (Rattus norvegicus); strain None; age None; sex None; n=50
Disease model
Ischemic and hemorrhagic brain lesions
MRI or image guidance method
MR imaging
Outcomes and Safety
Summary of Outcomes
Focused ultrasound with microbubbles at 558 kHz using burst sonications (10 ms bursts, 1 Hz PRF, 5 min total exposure) at acoustic powers 0.47–1.3 W produced focal ischemic or hemorrhagic brain lesions in rats. Shorter bursts (2 ms) or shorter sonication time (1 min) reduced lesion probability, while longer pulses (200 ms, 500 ms, or continuous wave) caused significant near-field damage.
Safety-related matter
Low-intensity focused ultrasound with microbubbles produced ischemic or hemorrhagic brain lesions at the focal volume, and longer pulses (200 ms, 500 ms, continuous wave) caused significant near-field damage; shorter bursts or shorter sonication reduced lesion probability. Use of microbubbles lowered required acoustic power and avoided skull heating issues.
Brain Region
Ultrasound Parameters
FUS Frequency
558 kHz
FUS Mode
pulsed
Pulse duration
10 ms
Duration of a single FUS session
5 min
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single session
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