This study explored the thermal conditions necessary for the vaporization of superheated perfluorocarbon nanodrops. Droplets C3F8 and C4F10 coated with a homologous series of saturated diacylphosphatidylcholines were formed by condensation of 4 μm diameter microbubbles. These drops were stable at room temperature and atmospheric pressure, but they vaporized back into microbubbles at higher temperatures. The vaporization transition was measured as a function of temperature by laser light extinction. We found that C3F8 and C4F10 drops experienced 90% vaporization at 40 and 75 °C, respectively, near the theoretical superheat limits (80-90% of the critical temperature). We therefore conclude that the metastabilty of these phase-change agents arises not from the droplet Laplace pressure altering the boiling point, as previously reported, but from the metastability of the pure superheated fluid to homogeneous nucleation. The rate of C4F10 drop vaporization was quantified at temperatures ranging from 55 to 75 °C, and an apparent activation energy barrier was calculated from an Arrhenius plot. Interestingly, the activation energy increased linearly with acyl chain length from C14 to C20, indicating that lipid interchain cohesion plays an important role in suppressing the vaporization rate. The vaporized drops (microbubbles) were found to be unstable to dissolution at high temperatures, particularly for C14 and C16. However, proper choice of the fluorocarbon and lipid species provided a nanoemulsion that could undergo at least ten reversible condensation/vaporization cycles. The vaporization properties presented in this study may facilitate the engineering of tunable phase-shift particles for diagnostic imaging, targeted drug delivery, tissue ablation, and other applications.

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The microbubble offers a unique platform to study lung surfactant mechanics at physiologically relevant geometry and length scale. In this study, we compared the response of microbubbles (∼15 μm initial radius) coated with pure dipalmitoyl-phosphatidylcholine (DPPC) versus naturally derived lung surfactant (SURVANTA) when subjected to linearly increasing hydrostatic pressure at different rates (0.5-2.3 kPa/s) at room temperature. The microbubbles contained perfluorobutane gas and were submerged in buffered saline saturated with perfluorobutane at atmospheric pressure. Bright-field microscopy showed that DPPC microbubbles compressed spherically and smoothly, whereas SURVANTA microbubbles exhibited wrinkling and smoothing cycles associated with buckling and collapse. Seismograph analysis showed that the SURVANTA collapse amplitude was constant, but the collapse rate increased with the pressurization rate. An analysis of the pressure-volume curves indicated that the dilatational elasticity increased during compression for both shell types. The initial dilatational elasticity for SURVANTA was nearly twice that of DPPC at higher pressurization rates (>1.5 kPa/s), producing a pressure drop of up to 60 kPa across the film prior to condensation of the perfluorobutane core. The strain-rate dependent stiffening of SURVANTA shells likely arises from their composition and microstructure, which provide enhanced in-plane monolayer rigidity and lateral repulsion from surface-associated collapse structures. Overall, these results provide new insights into lung surfactant mechanics and collapse behavior during compression.

Microbubbles (MBs) are micrometre sized gas spheres comprising a biocompatible shell that provide vascular contrast for diagnostic ultrasound (US) imaging. MBs volumetrically oscillate in an ultrasonic field and scatter acoustic energy over a range of frequencies that can be separated from the tissue response. MBs can also provide organ perfusion rates by imaging their “wash-in” to a region of interest which can be correlated to vascular flow. When driven at higher acoustic pressures, localized biological effects can be induced, including increased tissue permeabilization, thermal effects and localised release of drugs that can be encapsulated in the MBs themselves. Both hydrophobic and hydrophilic drugs can be loaded on to MBs e.g. through the use of liposomal carriers or direct attachment of drug molecules to the bubble shell. Since the early 2000s, MB-based technologies have been well researched, though there was significant regulatory push back starting in 2006 based on a controversial clinical trial. From that point, both physicians and researchers have consistently demonstrated the robust safety of MBs as ultrasound contrast agents and their significant clinical utility. Within the last 5 years, more indications have been approved. A recent first-in-man clinical trial of therapeutic US with MBs reversibly opening the blood brain barrier has also been shown to be safe in amyotrophic lateral sclerosis patients. The following article outlines the coupling of US and MBs as a diagnostic and therapeutic platform with a particular focus on their application to the therapy of surgical diseases.

The drive toward minimally invasive surgery has yielded multiple benefits for patients but has also increased the incidence of pseudoaneurysms (PSA). The current standard of care is ultrasound‐guided thrombin injection to coagulate blood in the PSA sac and seal the ruptured vessel. There is, however, a risk of downstream thrombosis if thrombin escapes into the communicating vessel and this limits patient eligibility for thrombin injection. In this study, the feasibility of using magnetic targeting to reduce the risk of distal thrombosis is investigated. Thrombin‐loaded magnetic microbubbles are formulated and injected into tissue‐mimicking phantoms of PSAs with different geometries using either saline or whole (equine) blood. Ultrasound imaging is used to quantify the concentration of bubbles remaining in the sac with and without application of a custom‐built magnetic array. An absorbance‐based assay is also used to quantify the concentration of thrombin escaping from the sac. Magnetic targeting enables a significant increase in thrombin retention in all femoral artery PSA models except one, with up to 97% ± 2.5% of the injected thrombin being retained. It is also confirmed that the enzymatic activity of thrombin is maintained, and that clot formation can be successfully achieved in whole blood.

Advances in magnetic materials have enabled the development of new therapeutic agents which can be localised by external magnetic fields. These agents offer a potential means of improving treatment targeting and reducing the toxicityrelated side effects associated with systemic delivery. Achieving sufficiently high magnetic fields at clinically relevant depths in vivo, however, remains a challenge. Similarly, there is a need for techniques for real-time monitoring that do not rely on magnetic resonance imaging (MRI). Here, we present a hand-held device to meet these requirements, combining an array of permanent magnets and a thin 64-element capacitive micromachined ultrasound transducer (CMUT) interfaced to a real-time imaging system.Drug carrier localisation was assessed by measuring the terminal velocity of magnetic microbubbles in a column of fluid above the magnetic array. It was found that the magnetic pull force was sufficient to overcome buoyancy at equivalent tissue depths of at least 35 mm and that the median terminal velocity ranged from 0.7 -20 µm/s over the distances measured. A Monte Carlo study was performed to estimate capture effectiveness in tumour microvessels over a range of different tissue depths and flow rates. Finally, B-mode and contrast-enhanced ultrasound imaging were demonstrated using a gel flow phantom containing a 1.6 mm diameter vessel. Real-time monitoring provided visual confirmation of retention of magnetic microbubbles along the vessel wall at a flow rate of 0.5 mL/min. These results indicate that the system can successfully retain and image magnetic microbubbles at tissue depths and flow rates relevant for clinical applications such as molecular ultrasound imaging of artherosclerosis, sonodynamic and antimetabolite cancer therapy, and clot dissolution via sonothrombolysis.

Background Of patients admitted to intensive care, 56% possess or will acquire acute respiratory failure (ARF) with slightly less than onethird of these patients progress to the most severe form of respiratory failure known as acute respiratory distress syndrome (ARDS) [1]. Effective methods of oxygen delivery are essential to improve outcomes in ARF and ARDS; however, with currently available medical treatments the mortality rate in these cases has been reported at 32-75% [1]. Therefore, research continues to look for more effective