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Polymer-shelled micro-bubbles are employed as ultrasound contrast agents (UCAs) and vesicles for targeted drug delivery. UCA-based delivery of the therapeutic payload relies on ultrasound-induced shell rupture. The fragility of two polymer-shelled UCAs manufactured by Point Biomedical or Philips Research was investigated by characterizing their response to static overpressure. The nominal diameters of Point and Philips UCAs were 3 μm and 2 μm, respectively. The UCAs were subjected to static overpressure in a glycerol-filled test chamber with a microscope-reticule lid. UCAs were reconstituted in 0.1 mL of water and added over the glycerol surface in contact with the reticule. A video-microscope imaged UCAs as glycerol was injected (5 mL/h) to vary the pressure from 2 to 180 kPa over 1 h. Neither UCA population responded to overpressure until the rupture threshold was exceeded, which resulted in abrupt destruction. The rupture data for both UCAs indicated three subclasses that exhibited different rupture behavior, although their mean diameters were not statistically different. The rupture pressures provided a measure of UCA fragility; the Philips UCAs were more resilient than Point UCAs. Results were compared to theoretical models of spherical shells under compression. Observed variations in rupture pressures are attributed to shell imperfections. These results may provide means to optimize polymeric UCAs for drug delivery and elucidate associated mechanisms. [ABSTRACT FROM AUTHOR]

This paper presents a combined ultrasound and photoacoustic (PA) imaging (PAI) system used to obtain high-quality, co-registered images of mouse-embryo anatomy and vasculature. High-frequency ultrasound (HFU, >20 MHz) is utilized to obtain high-resolution anatomical images of small animals while PAI provides high-contrast images of the vascular network. The imaging system is based on a 40 MHz, 5-element, 6 mm aperture annular-array transducer with a 800 μm diameter hole through its central element. The transducer was integrated in a cage-plate assembly allowing for a collimated laser beam to pass through the hole so that the optical and acoustic beams were collinear. The assembly was mounted on a two-axis, motorized stage to enable the simultaneous acquisition of co-registered HFU and PA volumetric data. Data were collected from all five elements in receive and a synthetic-focusing algorithm was applied in post-processing to beamform the data and increase the spatial resolution and depth-of-field (DOF) of the HFU and PA images. Phantom measurements showed that the system could achieve high-resolution images (down to 90 μm for HFU and 150 μm for PAI) and a large DOF of >8 mm. Volume renderings of a mouse embryo showed that the scanner allowed for visualizing morphologically precise anatomy of the entire embryo along with corresponding co-registered vasculature. Major head vessels, such as the superior sagittal sinus or rostral vein, were clearly identified as well as limb bud vasculature. [ABSTRACT FROM AUTHOR]

The Oak Ridge National Laboratory Spallation Neutron Source employs a high-energy pulsed proton beam incident on a mercury target to generate short bursts of neutrons. Absorption of the proton beam produces rapid heating of the mercury, resulting in the formation of acoustic shock waves and the nucleation of cavitation bubbles. The subsequent collapse of these cavitation bubbles promote erosion of the steel target walls. Preliminary measurements using two passive cavitation detectors (megahertz-frequency focused and unfocused piezoelectric transducers) installed in a mercury test target to monitor cavitation generated by proton beams with charges ranging from 0.041 to 4.1 μC will be reported on. Cavitation was initially detected for a beam charge of 0.082 μC by the presence of an acoustic emission approximately 250 μs after arrival of the incident proton beam. This emission was consistent with an inertial cavitation collapse of a bubble with an estimated maximum bubble radius of 0.19 mm, based on collapse time. The peak pressure in the mercury for the initiation of cavitation was predicted to be 0.6 MPa. For a beam charge of 0.41 μC and higher, the lifetimes of the bubbles exceeded the reverberation time of the chamber (∼300 μs), and distinct windows of cavitation activity were detected, a phenomenon that likely resulted from the interaction of the reverberation in the chamber and the cavitation bubbles. [ABSTRACT FROM AUTHOR]

A method for producing a prescribed acoustic pressure field from a piezoelectric array was investigated. The array consisted of 170 elements placed on the inner surface of a 15 cm radius spherical cap. Each element was independently driven by using individual pulsers each capable of generating 1.2 kV. Acoustic field customization was achieved by independently controlling the time when each element was excited. The set of time delays necessary to produce a particular acoustic field was determined by using an optimization scheme. The acoustic field at the focal plane was simulated by using the angular spectrum method, and the optimization searched for the time delays that minimized the least squared difference between the magnitudes of the simulated and desired pressure fields. The acoustic field was shaped in two different ways: the -6 dB focal width was increased to different desired widths and the ring-shaped pressure distributions of various prescribed diameters were produced. For both cases, the set of delays resulting from the respective optimization schemes were confirmed to yield the desired pressure distributions by using simulations and measurements. The simulations, however, predicted peak positive pressures roughly half those obtained from the measurements, which was attributed to the exclusion of nonlinearity in the simulations. [ABSTRACT FROM AUTHOR]

Measurements are presented of acoustic emissions from cavitation collapses on the surface of a synthetic kidney stone in response to shock waves (SWs) from an electrohydraulic lithotripter. A fiber optic probe hydrophone was used for pressure measurements, and passive cavitation detection was used to identify acoustic emissions from bubble collapse. At a lithotripter charging voltage of 20 kV, the focused SW incident on the stone surface resulted in a peak pressure of 43±6 MPa compared to 23±4 MPa in the free field. The focused SW incident upon the stone appeared to be enhanced due to the acoustic emissions from the forced cavitation collapse of the preexisting bubbles. The peak pressure of the acoustic emission from a bubble collapse was 34±15 MPa, that is, the same magnitude as the SWs incident on the stone. These data indicate that stresses induced by focused SWs and cavitation collapses are similar in magnitude thus likely play a similar role in stone fragmentation. [ABSTRACT FROM AUTHOR]

We investigate the role of secondary shock waves (SSWs) generated by cavitation in lithotripsy. Acoustic pressure was measured with a fiber optic probe hydrophone and cavitation using a dual passive cavitation detector (PCD) consisting of two confocal transducers. An artificial stone (∼7 mm diameter and ∼9 mm length) was placed at the focus of an electrohydraulic lithotripter. The fiber was inserted through a hole drilled through the stone so that the tip was at the proximal surface. SSWs were identified by matching the time of arrival to that of the inertial collapse signature acquired by the PCD. Measurements of SSWs were obtained for 50% of SWs fired at 20 kV and 1 Hz. The peak positive pressure for the SSW was p+=33.7±14.8 MPa, which was comparable to the pressure induced by the incident SW (p+=42.6±6 MPa). The peak pressure in water was p+=23.2±4.4 MPa. The PCD also recorded acoustic emissions from forced collapse of pre-existing bubbles caused by the incident SW. We propose that both the reflection from the semi-rigid stone boundary and SSW from the forced collapse contribute to the observed increase in the peak pressure of the incident SW in presence of a stone. [Work supported by NIH.] [ABSTRACT FROM AUTHOR]

We report measurements of a number of different shock wave therapy (SWT) devices. Two devices were electrohydraulic (EH): one had a large shock source (HMT Ossatron) and the other was a small hand-held source (HMT Evotron). The other device was a pneumatically driven device (EMS Swiss Dolorclast) and two different hand pieces were measured, one with an ‘‘unfocused’’ head and the other with a ‘‘focused’’ head. We found that the EH sources generated focused shock waves with a positive phase about 1 microsec long and peak pressure around 40 MPa, however, the acoustic output of the HMT Evotron appeared to be independent of the power setting of the machine. For the pneumatic source the duration of the positive phase was greater than 4 microsec and the peak pressure about 7 MPa. There was no clear shock front present and the waveform had a complex tail structure that was dependent on the power setting of the machine. We found that the focused hand-piece did not generate a focused acoustic field. The results are compared to reports of measurements from electromagnetic SWT devices. We contrast measurements made with different hydrophone systems: fiber-optic probe hydrophone, PVDF membrane hydrophone and PVDF bullet-shaped hydrophone. [ABSTRACT FROM AUTHOR]