Time-reversal acoustics and ultrasound-assisted convection-enhanced drug delivery to the brain.
Authors: Olbricht W, Sistla M, Ghandi G, Lewis G, Sarvazyan A
Time-reversal acoustics is an effective way of focusing ultrasound deep inside heterogeneous media such as biological tissues. Convection-enhanced delivery is a method of delivering drugs into the brain by infusing them directly into the brain interstitium. These two technologies are combined in a focusing system that uses a "smart needle" to simultaneously infuse fluid into the brain and provide the necessary feedback for focusing ultrasound using time-reversal acoustics. The effects of time-reversal acoustics-focused ultrasound on the spatial distribution of infused low- and high-molecular weight tracer molecules are examined in live, anesthetized rats. Results show that exposing the rat brain to focused ultrasound significantly increases the penetration of infused compounds into the brain. The addition of stabilized microbubbles enhances the effect of ultrasound exposure.
Introduction
Purpose
Drug delivery WITHOUT BBB opening
Study Objective
To evaluate whether time-reversal acoustics–focused ultrasound delivered via a smart needle enhances penetration and spatial distribution of infused low- and high-molecular-weight tracers in rat brain, and whether microbubbles augment this effect.
Animal model / Human subject
Rat (Rattus norvegicus), strain: not specified, age: not specified, sex: not specified
Disease model
Healthy
MRI or image guidance method
Time-reversal acoustics using feedback from a 'smart needle' (no MRI/image guidance)
Cargo name and characteristics
Tracer molecules (low-molecular-weight and high-molecular-weight tracers; small-molecule and high-MW tracer compounds)
Route of administration
Intracerebral infusion (convection-enhanced delivery / direct infusion into brain interstitium via a needle)
Outcomes and Safety
Summary of Outcomes
Time-reversal acoustics-focused ultrasound during convection-enhanced delivery significantly increased penetration of both low- and high-molecular-weight tracer molecules into rat brain. The addition of stabilized microbubbles further enhanced the ultrasound-induced increase in tracer penetration.
Safety-related matter
No adverse effects or safety concerns are mentioned in the provided text; the paper reports only increased tracer penetration and enhancement by microbubbles in anesthetized rats.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
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