Simultaneous Ultrasound Therapy and Monitoring of Microbubble-Seeded Acoustic Cavitation Using a Single-Element Transducer

Abstract

Ultrasound-driven microbubble (MB) activity is used in therapeutic applications such as blood clot dissolution and targeted drug delivery. The safety and performance of these technologies are linked to the type and distribution of MB activities produced within the targeted area, but controlling and monitoring these activities in vivo and in real time has proven to be difficult. As therapeutic pulses are often milliseconds long, MB monitoring currently requires a separate transducer used in a passive reception mode. Here, we present a simple, inexpensive, integrated setup, in which a focused single-element transducer can perform ultrasound therapy and monitoring simultaneously. MBs were made to flow through a vessel-mimicking tube, placed within the transducer's focus, and were sonicated with therapeutic pulses (peak rarefactional pressure: 75-827 kPa, pulse lengths: [Formula: see text] and 20 ms). The MB-seeded acoustic emissions were captured using the same transducer. The received signals were separated from the therapeutic signal with a hybrid coupler and a high-pass filter. We discriminated the MB-generated cavitation signal from the primary acoustic field and characterized MB behavior in real time. The simplicity and versatility of our circuit could make existing single-element therapeutic transducers also act as cavitation detectors, allowing the production of compact therapeutic systems with real time monitoring capabilities.

Temporal Stability of Lipid-Shelled Microbubbles During Acoustically-Mediated Blood-Brain Barrier Opening

“…We also assumed a dimensionless resistance value of 1 for simplicity, therefore energy units are given in V 2 s and not in Joule. Control sonications without MBs were used to estimate the baseline signal [58], whose energy was subtracted from the MB acoustic emissions at each time point [43]. We then assessed the normalized cumulative energy (Figure 2C) to investigate the temporal distribution of cavitation emissions during the pulse.…”

Pulse inversion enhances the passive mapping of microbubble-based ultrasound therapy

“…1). The strong odd harmonics were mainly produced due to the high transmit transfer function of the therapeutic transducer at these frequencies, 12 following the application of a broadband single-cycle voltage pulse, and partially due to non-linear ultrasound propagation.…”

“…11 PCD can be performed using two separate co-aligned transducers 6,11 or a single transducer. 12 Using linear or hemispherical arrays, one can localize the spatial location of the acoustic sources to perform cavitation mapping during therapy. 7,13,14 Passive imaging techniques can be used to monitor ultrasound therapies at arbitrary pulse lengths; however, their axial resolution remains poor despite recent advances.…”