Search

Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor – a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 μL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.

Microbubbles are used as contrast agents in clinical ultrasound for Left Ventricular Opacification (LVO) and perfusion imaging. They are also the subject of promising research in therapeutics as a drug delivery mechanism or for sonoporation and co-administration. For maximum efficacy in these applications, it is important to understand the acoustic characteristics of the administered microbubbles. Despite this, there is significant variation in the experimental procedures and equipment used to measure the acoustic properties of microbubble populations. A chamber was designed to facilitate acoustic characterisation experiments and was manufactured using additive manufacturing techniques. The design has been released to allow wider uptake in the research community. The efficacy of the chamber for acoustic characterisation has been explored with an experiment to measure the scattering of SonoVue® microbubbles at the fundamental frequency and second harmonic under interrogation from emissions in the frequency range of 1.6 to 6.4 MHz. The highest overall scattering values were measured at 1.6 MHz and decreased as the frequency increased, a result which is in agreement with previously published measurements. Statistical analysis of the acoustic scattering measurements have been performed and a significant difference, at the 5% significance level, was found between the samples containing contrast agent and the control sample containing only deionised water. These findings validate the proposed design for measuring the acoustic scattering characteristics of ultrasound contrast agents.

As an alternative to delay-and-sum beamforming, a novel beamforming technique called filtered-delay multiply and sum (FDMAS) was introduced recently to improve ultrasound B-mode image quality. Although a considerable amount of work has been performed to evaluate FDMAS performance, no study has yet focused on the beamforming step size, , in the lateral direction. Accordingly, the performance of FDMAS was evaluated in this study by fine-tuning to find its optimal value and improve boundary definition when balloon snake active contour (BSAC) segmentation was applied to a B-mode image in ultrafast imaging. To demonstrate the effect of altering in the lateral direction on FDMAS, measurements were performed on point targets, a tissue-mimicking phantom and in vivo carotid artery, by using the ultrasound array research platform II equipped with one 128-element linear array transducer, which was excited by 2-cycle sinusoidal signals. With 9-angle compounding, results showed that the lateral resolution (LR) of the point target was improved by 67.9% and 81.2%, when measured at −6 dB and −20 dB respectively, when was reduced from to . Meanwhile the image contrast ratio (CR) measured on the CIRS phantom was improved by 10.38 dB at the same reduction and the same number of compounding angles. The enhanced FDMAS results with lower side lobes and less clutter noise in the anechoic regions provides a means to improve boundary definition on a B-mode image when BSAC segmentation is applied.

This paper proposes a new approach to determine the depth and location of buried pipelines using the remote magnetic field measured by aboveground magnetometer surveys. Calculation is presented and verified by the experimental results on 152-mm (6-in.). steel vessels. Performance of the technique is also evaluated through field trials against industrial pipe locators. The depth calculated from the measured magnetic field using this proposed technique agreed within the tolerance interval representing the confidence level of 99.7% of the depth determined by the industrial devices and was able to trend changes of the buried depth. In addition, it was possible to map the target pipeline using the survey route coordinates by calculating the lateral position of the survey route relative to the pipeline centerline from the measured magnetic field. So far, the depth measured by this proposed technique has shown a potential error of 8%. By producing a three-dimensional profile of buried pipelines through quick aboveground surveys, the proposed technique can be considered as a screening technique for asset and integrity management such as monitoring geohazard conditions.

The production and stability of microbubbles (MBs) is enhanced by increasing the viscosity of both the formation and storage solution, respectively. Glycerol is a good candidate for biomedical applications of MBs, since it is biocompatible, although the exact molecular mechanisms of its action is not fully understood. Here, we investigate the influence glycerol has on lipid-shelled MB properties, using a range of techniques. Population lifetime and single bubble stability were studied using optical microscopy. Bubble stiffness measured by AFM compression is compared with lipid monolayer behavior in a Langmuir–Blodgett trough. We deduce that increasing glycerol concentrations enhances stability of MB populations through a 3-fold mechanism. First, binding of glycerol to lipid headgroups in the interfacial monolayer up to 10% glycerol increases MB stiffness but has limited impact on shell resistance to gas permeation and corresponding MB lifetime. Second, increased solution viscosity above 10% glycerol slows down the kinetics of gas transfer, markedly increasing MB stability. Third, above 10%, glycerol induces water structuring around the lipid monolayer, forming a glassy layer which also increases MB stiffness and resistance to gas loss. At 30% glycerol, the glassy layer is ablated, lowering the MB stiffness, but MB stability is further augmented. Although the molecular interactions of glycerol with the lipid monolayer modulate the MB lipid shell properties, MB lifetime continually increases from 0 to 30% glycerol, indicating that its viscosity is the dominant effect on MB solution stability. This three-fold action and biocompatibility makes glycerol ideal for therapeutic MB formation and storage and gives new insight into the action of glycerol on lipid monolayers at the gas–liquid interface.

Gold nanorods (AuNRs) can be synthesised with different sizes but similar aspect ratios and therefore similar surface plasmon resonances (SPRs). Their strong optical absorbance governed by their SPRs facilitates their ability to be used as molecular-targeted contrast agents for photoacoustic (PA) imaging. The size of AuNRs has an effect on the PA conversion efficiency, melting threshold, and cytotoxicity, indicating that size can have a significant impact on overall biomedical efficacy. We investigated these factors for four different AuNRs (widths of 10, 25, 40 and 50 nm) all with SPRs of 815 ± 26 nm. A size-dependent linear relationship between fluence and PA amplitude was observed, along with particle melting. Reshaping was confirmed via transmission electron microscopy and spectrophotometry at a laser fluence of 11 ± 1.7 mJ cm−2, 20 ± 2.2 mJ cm−2, and 40 ± 2.6 mJ cm−2. Cytotoxicity was tested on lung cancer cells (A549) via a colourimetric assay at a maximum concentration of 3 × 1010 NP ml−1. Results demonstrate the 40 nm and 50 nm AuNRs produced the highest signal for equivalent particle numbers, but displayed the highest toxicity. Conversely, the 10 nm AuNRs were the most efficient photoacoustic converters, at equivalent total mass. This study demonstrates the importance of AuNR size and concentration on selection of AuNRs for their eventual clinical use.

The importance of the excitation bandwidth is well known in diagnostic ultrasound imaging. However, the effect of excitation bandwidth in therapeutic applications of microbubbles has been mostly overlooked. A majority of contrast agent production techniques generate polydisperse microbubble populations, so a wide range of resonance frequencies exist. Therefore, wideband excitation is necessary to fully utilize microbubble resonance behavior and maximize the reradiated energy from a microbubble population, both for imaging and therapy. Oscillations of sixty SonoVue microbubbles in proximity of a rigid boundary were captured on a high speed camera at 3 Mfps, excited with a peak negative pressure of 50 kPa at 1 MHz. Measurements were analyzed according to their peak radiated pressure, radial oscillations, root mean squared pressure, and shear stress generated by microbubbles. Results showed that long duration and wideband excitation at low intensity levels was preferable for sonoporation, where microbubbles can be driven in a stable oscillation state without experiencing inertial cavitation or destruction.

High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5–35 dB for peak negative pressures between 1.19–3.19 ± 0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2–2.71 ± 0.01 MPa at a fluence of 3.4 mJ ${\rm cm}^{-2}$ . Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of $1.5 \times 10^3$ a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as providing the ability to identify and treat small multi-focal cancerous regions with minimal damage to surrounding healthy tissue.

Wave propagation in granular chains is subject to dispersive effects as well as to nonlinear effects arising from the Hertzian contact law. This enables the formation of wideband pulses, which is a desirable feature in the context of diagnostic and therapeutic ultrasound applications. However, coupling of the ultrasonic energy from a chain of spheres into biological tissue is a big challenge. In order to improve the energy transfer efficiency into biological materials, a matching layer is required. A prototype device was designed to address this by using six aluminium spheres and a vitreous carbon matching layer. The matching layer and the pre-compression force are selected specifically to maximise the acoustic pressure in water and its bandwidth. The designed device generated a train of wideband ultrasonic pulses from a narrowband input with a centre frequency of 73 kHz. An analytical model was created to simulate the behaviour of a matching layer as a flexible thin plate clamped from the edges. This model was then verified using free field hydrophone measurements in water, which successfully predicted the increased bandwidth by generation of harmonics. The shapes of the measured and the predicted waveforms were compared by calculating the normalised cross-correlation, which showed 83\% similarity between both. Since the generation of harmonics are of interest for this study, the total harmonic distortion (THD) and the -6~dB bandwidth of the signals were used to analyse signal fidelity between the hydrophone measurements and the model predictions. The acoustic signals in water had a root mean squared THD of 73\% and the model predicted a root mean squared THD of 78\%. The -6~dB bandwidths of individual pulses measured by a hydrophone and predicted with the model were 280~kHz and 252~kHz, respectively. At these high ultrasonic frequencies, it is the first experimental demonstration of resonant chains operating in water with a matching layer.\ud \ud

The present work analyzes multi-relay full-duplex systems with relay selection under multipath fading conditions in the context of channel capacity under: i) optimum power and rate adaptation; ii) truncated channel inversion with fixed rate. Useful analytic expressions are derived for these measures as well as for the associated optimum cut-off level. The offered results are then employed in the analysis of the corresponding end-to-end performance by also quantifying the effects of the involved relay self-interference. It is shown that high capacity levels are achieved even for a moderate number of relays and self-interference levels, at no considerably added system complexity. This is particularly useful in demanding emerging applications that are subject to transmit power constraints or fixed rate requirements. publishedVersion

This paper investigates the characteristics of the shadowed fading observed in off-body communications channels at 5.8 GHz. This is realized with the aid of the κ-μ/gamma composite fading model, which assumes that the transmitted signal undergoes κ-μ fading, which is subject to multiplicative shadowing. Based on this, the total power of the multipath components, including both the dominant and scattered components, is subject to non-negligible variations that follow the gamma distribution. For this model, we present an integral form of the probability density function (PDF) as well as important analytic expressions for the PDF, cumulative distribution function, moments, and moment generating function. In the case of indoor off-body communications, the corresponding measurements were carried out in the context of four explicit individual scenarios, namely: line of sight (LOS), non-LOS walking, rotational, and random movements. The measurements were repeated within three different indoor environments and considered three different hypothetical body worn node locations. With the aid of these results, the parameters for the κ-μ/gamma composite fading model were estimated and analyzed extensively. Interestingly, for the majority of the indoor environments and movement scenarios, the parameter estimates suggested that dominant signal components existed even when the direct signal path was obscured by the test subject's body. In addition, it is shown that the κ-μ/gamma composite fading model provides an adequate fit to the fading effects involved in off-body communications channels. Using the Kullback-Leibler divergence, we have also compared our results with another recently proposed shadowed fading model, namely, the κ-μ/lognormal LOS shadowed fading model. It was found that the κ-μ/gamma composite fading model provided a better fit for the majority of the scenarios considered in this paper.

It is demonstrated that broad-bandwidth ultrasonic signals containing frequency components in excess of 200 kHz can be created in spherical chains using harmonic excitation at 73 kHz. Multiple reflections created a periodic waveform containing both harmonics and sub-harmonics of the original forcing frequency, due to non-linear Hertzian contact. These discrete frequencies represented some of the many allowed non-linear normal modes of vibration of the whole chain. Excitation at a single fixed frequency could thus be used to produce wide-bandwidth impulses for different lengths of spherical chains. Experimental results were in good agreement with theoretical predictions.\ud

Energy detection (ED) is a simple and popular method of spectrum sensing in cognitive radio systems. It is also widely known that the performance of sensing techniques is largely affected when users experience fading effects. This paper investigates the performance of an energy detector over generalized κ-μ and κ- μ extreme fading channels, which have been shown to provide remarkably accurate fading characterization. Novel analytic expressions are firstly derived for the corresponding average probability of detection for the case of single-user detection. These results are subsequently extended to the case of square-law selection (SLS) diversity and for collaborative detection scenarios. As expected, the performance of the detector is highly dependent upon the severity of fading since even small variations of the fading conditions affect significantly the value of the average probability of detection. Furthermore, the performance of the detector improves substantially as the number of branches or collaborating users increase in both severe and moderate fading conditions, whereas it is shown that the κ- μ extreme model is capable of accounting for fading variations even at low signal-to-noise values. The offered results are particularly useful in assessing the effect of fading in ED-based cognitive radio communication systems; therefore, they can be used in quantifying the associated tradeoffs between sensing performance and energy efficiency in cognitive radio networks.μ