A combined magnetic-acoustic device for simultaneous, co-aligned application of magnetic and ultrasonic fields

Acoustically-responsive microbubbles have been widely researched as agents for both diagnostic and therapeutic applications of ultrasound. Recently, there has also been considerable interest in magnetically functionalised microbubbles as multi-modality imaging agents and carriers for magnetically targeted drug delivery. The latter application in particular requires simultaneous application of magnetic and acoustic fields to a target region. This can present a significant practical challenge, especially in vivo where access is typically limited. 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 then to activate them acoustically. For the purposes of this proof of concept study, the magnetic component of 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. The ultrasound transducer was designed to maximise the acoustic intensity in the same region in order to induce cavitation of the magnetically captured microbubbles. Previous studies have indicated that both microbubble concentration and duration of cavitation activity are positively correlated with therapeutic effect. The ability of the device to trap and activate microbubbles was therefore assessed by a series of in vitro tests in a tissue mimicking phantom containing a single vessel of 1.2 mm diameter. At a flow rate of 4.2 mm/s magnetic trapping produced an increase in intensity under B-mode ultrasound imaging consistent with the predicted accumulation profile. When the microbubbles were exposed to the ultrasound field from the probe, the resulting 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.