The superior scattering properties of gas bubbles compared with blood cells have made microbubble ultrasound contrast agents important tools in ultrasound diagnosis. Over the past 2 years they have become the focus of a wide and rapidly expanding field of research, with their benefits being repeatedly demonstrated, both in ultrasound image enhancement, and more recently in drug and gene delivery applications. However, despite considerable investigation, their behaviour is by no means fully understood and, while no definite evidence of harmful effects has been obtained, there remain some concerns as to their safety. In this review the existing theoretical and experimental evidence is examined in order to clarify the extent to which contrast agents are currently understood and to identify areas for future research. In particular the disparity between the conditions considered in theoretical models and those encountered both in vitro, and more importantly in vivo is discussed, together with the controversy regarding the risk of harmful bio-effects.

A problem with tissue engineering scaffolds is maintaining seeded cell viability and function due to limitations of oxygen and nutrient transfer. An approach to maintain suitable oxygen concentrations throughout the scaffold would be to controllably incorporate microchannelling within these scaffolds. This study investigated the incorporation of unidirectionally aligned soluble phosphate based glass fibers (PGF) into dense collagen scaffolds. PGF are degradable, and their degradation can be controlled through their chemistry and dimensions. Plastic compression was used to produce composite scaffolds at three different weight percentage while maintaining greater than 80% resident cell viability. PGF-collagen scaffold composition was quantified through thermogravimetric analysis as well as being morphologically and mechanically characterized. PGF degradation was measured through ion chromatography, and channel formation was verified with ultrasound imaging and SEM. The free movement of coated microbubble agents confirmed the channels to be continuous in nature and of 30-40 microm diameter. These microchannels in dense native collagen matrices could play an important role in hypoxia/perfusion limitations and also in the transportation of nutrients and potentially forming blood vessels through dense implants.

The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble.

A novel design for continuous flow sonocrystallization of adipic acid in a capillary device is presented and investigated experimentally and numerically. The effect of supersaturation and ultrasound power is studied. To elucidate the relationship between crystallization and cavitation, sonochemiluminescence and sonoemulsification experiments are performed, and numerical investigation of the wave propagation in aqueous solution is used to predict the probability of cavitation. Crystal size distribution at different operating conditions is obtained by laser diffraction. Narrow size distributions, small mean size of crystals (ca. 15 μm), and high crystal production rate are achieved when applying ultrasound. In addition, numerical simulations of pressure distribution show that high pressure amplitudes are obtainable near the vicinity of the sonoprobe tip. Using a cavitation threshold formulation, the distance from the tip where transient cavitation takes place is quantified. The results are in agreement with the experimental findings, in which by increasing the distance between capillary and sonoprobe, emulsification, sonochemiluminescence, and nucleation decrease. It is concluded that transient cavitation of bubbles is a significant mechanism for enhancing nucleation of crystals among the several proposed in the literature.

Appreciation for the medical and research potential of ultrasound neuromodulation is growing rapidly, with potential applications in non-invasive treatment of neurodegenerative disease and functional brain mapping spurring recent progress. However, little progress has been made in our understanding of the ultrasound-tissue interaction. The current study tackles this issue by measuring compound action potentials (CAPs) from an ex vivo crab walking leg nerve bundle and analysing the acoustic nature of successful stimuli using a passive cavitation detector (PCD). An unimpeded ultrasound path, new acoustic analysis techniques and simple biological targets are used to detect different modes of cavitation and narrow down the candidate biological effectors with high sensitivity. In the present case, the constituents of unmyelinated axonal tissue alone are found to be sufficient to generate de novo action potentials under ultrasound, the stimulation of which is significantly correlated to the presence of inertial cavitation and is never observed in its absence.