A Combined Magnetic‐Acoustic Device for Simultaneous, Coaligned Application of Magnetic and Ultrasonic Fields

Lester C Barnsley,Michael D Gray,Estelle Beguin,Eleanor Stride,Dario Carugo

doi:10.1002/admt.201800081

Abstract

AbstractAcoustically‐responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. There has also been considerable interest in magnetically‐functionalised microbubbles as multi‐modality imaging agents and carriers for targeted drug delivery. In this paper, we present a design for an integrated device capable of generating co‐aligned magnetic and acoustic fields in order to accumulate microbubbles at a specific location and to activate them acoustically. For this proof‐of‐concept study, the device was designed to concentrate microbubbles at a distance of 10 mm from the probe's surface, commensurate with relevant tissue depths in preclinical small animal models. Previous studies have indicated that both microbubble concentration and duration of cavitation activity are positively correlated with therapeutic effect. The utility of the device was assessed in vitro tests in a tissue‐mimicking phantom containing a single vessel (1.2 mm diameter). At a peak fluid velocity of 4.2 mm s−1 microbubble accumulation was observed under B‐mode ultrasound imaging and the corresponding cavitation activity was sustained for a period more than 4 times longer than that achieved with an identical acoustic field but in the absence of a magnet. The feasibility of developing a larger scale device for human applications is discussed.

Highlights

Acoustically-responsive microbubbles have been widely researched as agents renewed interest with the advent of superfor both diagnostic and therapeutic applications of ultrasound
The magnet consisted of two parts made from N52 grade NdFeB permanent magnet material designed so that they would only self-assemble in one stable configuration due to dipole interactions
We have previously shown that, the force from optimized magnet designs typically decays exponentially with distance, a Halbach array with a volume of 1000 cm3 would be capable of generating a field of 0.1 T and a normalized force of ≈4 T m−1 at a range of 50 mm.[28]

Summary

Introduction

Acoustically-responsive microbubbles have been widely researched as agents renewed interest with the advent of superfor both diagnostic and therapeutic applications of ultrasound. MDT is seen as a promising co-aligned magnetic and acoustic fields in order to accumulate microbubbles at means of improving the effectiveness of a specific location and to activate them acoustically. For this proof-of-concept therapy noninvasively and reducing the study, the device was designed to concentrate microbubbles at a distance of 10 mm from the probe’s surface, commensurate with relevant tissue depths in preclinical small animal models. At a peak fluid velocity of 4.2 mm s−1 microbubble accumulation was observed under B-mode ultrasound imaging and the corresponding cavitation activity was sustained for a period more than 4 times longer than that achieved ingly apparent that the magnet must be designed to generate a sufficient magnetic force over the target region to capture a therapeutically relevant quantity of carrier particles from the circulatory system.[7–. Microbubbles have been used clinically for decades as an ultrasound contrast agent due to their strong, nonlinear response to acoustic fields.[13,14] microbubbles can be formulated to carry bioactive molecules,[15,16] and uti-

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