Passive acoustic mapping of magnetic microbubbles for cavitation enhancement and localization

Abstract

Magnetic targeting of microbubbles functionalized with superparamagnetic nanoparticles has been demonstrated previously for diagnostic (B-mode) ultrasound imaging and shown to enhance gene delivery in vitro and in vivo. In the present work, passive acoustic mapping (PAM) was used to investigate the potential of magnetic microbubbles for localizing and enhancing cavitation activity under focused ultrasound. Suspensions of magnetic microbubbles consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), air and 10 nm diameter iron oxide nanoparticles were injected into a tissue mimicking phantom at different flow velocities (from 0 to 50 mm s(-1)) with or without an applied magnetic field. Microbubbles were excited using a 500 kHz single element focused transducer at peak negative focal pressures of 0.1-1.0 MPa, while a 64 channel imaging array passively recorded their acoustic emissions. Magnetic localization of microbubble-induced cavitation activity was successfully achieved and could be resolved using PAM as a shift in the spatial distribution and increases in the intensity and sustainability of cavitation activity under the influence of a magnetic field. Under flow conditions at shear rates of up to 100 s(-1) targeting efficacy was maintained. Application of a magnetic field was shown to consistently increase the energy of cavitation emissions by a factor of 2-5 times over the duration of exposures compared to the case without targeting, which was approximately equivalent to doubling the injected microbubble dose. These results suggest that magnetic targeting could be used to localize and increase the concentration of microbubbles and hence cavitation activity for a given systemic dose of microbubbles or ultrasound intensity.

Delivery of bevacizumab to atheromatous porcine carotid tissue using echogenic liposomes

“…Other locations relative to the axial location of sustained cavitation activity, downstream of the axial location analyzed, may have experienced more robust bevacizumab delivery. Strategies enabling a broader field of view of drug distributions, such as micro-CT (Ekdawi et al, 2015), two-photon (Nhan et al, 2013), or intravital (Dewhirst et al, 2002) microscopy, together with the recent development of cavitation imaging (Salgaonkar et al, 2009; Haworth et al, 2012; Arvanitis et al, 2014; Crake et al, 2015)—a passive acoustic technique used to provide a spatial map of spectral indicators of cavitation—may provide a more comprehensive view of the temporal and spatial relationship between cavitation and drug delivery. The cavitation measured in this study corresponded to cavitation throughout the lumen of the vessel.…”

Ultrasound‐Enhanced siRNA Delivery Using Magnetic Nanoparticle‐Loaded Chitosan‐Deoxycholic Acid Nanodroplets

“…The transducer featured a rectangular cutout through which an imaging linear array (model L11-4v; Verasonics Inc., USA) was aligned. [25] Samples were exposed to 10 s of ultrasound (pulse center frequency of 500 kHz, 1 MPa peak-to-peak focal pressure, 40 cycles per burst, 1 kHz pulse repetition frequency [26] ) at five points 3 mm apart, while the imaging array passively recorded the acoustic www.advhealthmat.de www.advancedsciencenews.com emissions from every 10th burst for the first second of each exposure (100 frames, 128 channels, 170 µs per run) to an ultrasound research platform (Verasonics V1; Verasonics Inc., USA) for subsequent analysis. After ultrasound exposure, cells were further incubated at 37 °C for 24 h. The number of viable cells was determined using the MTS colorimetric assay.…”

Quantitative Frequency-Domain Passive Cavitation Imaging

“…Passive cavitation imaging has been reported on multiple systems, including those produced by Zonare Medical Systems (Z.one Imaging System, Mountain View, CA, USA) [30], [33]–[35], [39], [40], [45], [49], [61], Ardent Sound (Iris 2 Ultrasound Imaging System, Mesa, AZ, USA) [31], [37], Terason (Terason 2000 Ultrasound System, Burlington, MA, USA) [32], Verasonics (V-1 and Vantage sytems, Bothell, WA, USA) [36], [38], [42], [47], [59], and Ultrasonix, now BK Ultrasound, (SonixDAQ, Richmond, BC, Canada) [52], [54]. Some of the systems, such as the Z.one, Vantage, and Sonix-DAQ provide direct access to pre-beamformed radio frequency or in-phase and quadrature signals so that the beamforming can be performed using the researchers’ algorithms.…”

“…Direct access to pre-beamformed signals provides researchers with more flexibility in beamforming, such as windowing, apodization, and nonlinear approaches. These systems have been used to beamform emissions induced by pulsed ultrasound at a variety of duty cycles [45]–[47], [49], [53], [61]. …”