Ultrasonic humidifiers use sound vibrations at frequencies higher than can be heard by humans (> 20,000 Hz) to generate aerosolized water also have potential for inducing sonochemical reactions for chemicals present in water. This research focuses on examining oxidants formed within ultrasonic humidifiers, as well as the oxidants effects of contaminants in water used in the systems. Hydroxyl radicals were found using DMPO as a spin trap. Caffeine and 17β-estradiol, as pharmaceutical contaminants of drinking water, were both emitted from the humidifier when present in the water reservoir and would enter breathing air. Emitted 17β-estradiol was found at 60% of the initial concentration filled in the ultrasonic humidifier after 480 minutes. Caffeine exhibited less degradation than 17β-estradiol. Degradation of both pharmaceuticals was attributed to ultrasonic processes, most likely oxidation with hydroxyl radicals produced. Bromide as a contaminant of the fill water was found to remain constant over time. / MS / Ultrasonic humidifiers carry health benefits from humidified air, but also have potential for chemical reactions within the systems that can impact human health. This research focuses on examining oxidants formed in ultrasonic humidifiers, as well as the degradation of contaminants in water used in the ultrasonic humidifiers. Hydroxyl radicals were found to be generated within the humidifier system. Caffeine and 17β-estradiol, a common estrogen, are possible contaminants in drinking water, which may be used to fill a humidifier. Both were introduced and emitted from the ultrasonic humidifier. Emitted 17β-estradiol was found at 60% of the initial concentration filled in the ultrasonic humidifier at the start of 8 hours. Degradation of both pharmaceuticals was attributed to ultrasonic processes, most likely oxidation with hydroxyl radicals produced.

A reticulonodular splenic pattern is commonly associated with neoplastic or infectious etiologies. However, this has been described as an age-related variant in both humans and dogs, likely representing lymphoid follicles. The purpose of this study was to determine whether the ultrasonographic appearance of the spleens of growing kittens mimics the canine presentation. This was a prospective, descriptive study design. Healthy kittens up to 18 months old were scanned using a high frequency linear transducer. A reticulonodular pattern was present in (89%) of spleens. After 4 months of age, there was an overall negative correlation with age and the grade of the imaged spleen, which persisted even amongst the kittens that were enrolled serially. The findings of this study suggest that a reticulonodular pattern in young cats and kittens may be a normal finding within this population.

Yes / The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable Combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC-MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery. / The work was funded by the Medical Research Council (grant number: MR/L01629X MRC Medical Bioinformatics Centre) and the EPSRC (grant number EP/P023266/1 Health Impact Partnership). EPSRC (EP/I000623/1, EP/K023845/1). Laura E. McVeigh was funded by an EPSRC PhD Studentship (EP/L504993/1).

Yes / Advanced drug delivery systems, such as ultrasound-mediated drug delivery, show great promise for increasing the therapeutic index. Improvements in delivery by altering the ultrasound parameters have been studied heavily in vitro but relatively little in vivo. Here, the same therapeutic microbubble and tumour type are used to determine whether altering ultrasound parameters can improve drug delivery. Liposomes were loaded with SN38 and attached via avidin: biotin linkages to microbubbles. The whole structure was targeted to the tumour vasculature by the addition of anti-vascular endothelial growth factor receptor 2 antibodies. Tumour drug delivery and metabolism were quantified in SW480 xenografts after application of an ultrasound trigger to the tumour region. Increasing the trigger duration from 5 s to 2 min or increasing the number of 5 s triggers did not improve drug delivery, nor did changing to a chirp trigger designed to stimulate a greater proportion of the microbubble population, although this did show that the short tone trigger resulted in greater release of free SN38. Examination of ultrasound triggers in vivo to improve drug delivery is justified as there are multiple mechanisms at play that may not allow direct translation from in vitro findings. In this setting, a short tone burst gives the best ultrasound parameters for tumoural drug delivery. / This research was funded by the EPSRC (EP/I000623/1, EP/L504993/1 and EP/P023266/1). S.D.E. is supported by the National Institute for Health Research infrastructure at Leeds. J.R.M. is supported by an EPSRC UKRI Innovation Fellowship (EP/S001069/1).

Yes / An ultrasound sensor system has been applied to the mould of both the water and gas assisted injection moulding processes. The mould has a cavity wall mounted pressure sensor and instrumentation to monitor the injection moulding machine. Two ultrasound sensors are used to monitor the arrival of the fluid (gas or water) bubble tip through the detection of reflected ultrasound energy from the fluid polymer boundary and the fluid bubble tip velocity through the polymer melt is estimated. The polymer contact with the cavity wall is observed through the reflected ultrasound energy from that boundary. A theoretically based estimation of the residual wall thickness is made using the ultrasound reflection from the fluid (gas or water) polymer boundary whilst the samples are still inside the mould and a good correlation with a physical measurement is observed.

Ultrasonic wave propagation through a two-dimensional nonreciprocal phononic crystal with asymmetric aluminum rods in viscous water is studied for its application in Anderson localization and trapping of acoustic energy. A one-dimensional disorder in the otherwise 2D periodic crystal is introduced by disorienting the asymmetric rods along the rows and by keeping them equally oriented along the columns. An exponential decay of sound waves travelling along the direction of disorder is observed demonstrating Anderson localization whereas sound propagates as extended wave along the ordered direction. Localization length for the case of strong disorder with high randomness in the orientation of rods and weak disorder with weak fluctuations in the orientation of rods is evaluated. The degree of randomness in the orientation of the rods controls the localization length of the wave. Thouless's theoretical prediction for the scaling of Lyapunov exponent with disorder is experimentally observed for weak disorder at frequency in the transmission band and anomalous scaling is observed for band edge frequency. Transmission spectra of acoustic waves is also measured for opposite direction of propagation and nonreciprocity is observed for the exponentially weak transmission in the disordered direction as well as for extended states in the ordered direction. Breaking of reciprocity in the current structure is due to the broken PT symmetry. The T symmetry or the time reversal symmetry is broken by the viscous dissipation at the boundaries of scatterers and the water, and the P symmetry is broken by the asymmetric shape of the rods. Acoustic energy trapping inside a nonreciprocal phononic crystal cavity is studied by creating three configurations of cavities. These configurations are based on the orientation of the asymmetric scatterers on each side of the cavity. Only one of these configuration utilizes the nonreciprocal property of the structure. Enhancement of energy trapping in the cavity is observed for the cavity orientation utilizing nonreciprocity. The proposed enhancement of energy trapping occurs at the transmission band frequency unlike the extensively used mechanism of energy trapping at the defect modes of the band gap of the phononic crystal. All the experimental results are verified numerically using finite element based modelling in COMSOL Multiphysics. The proposed devices can be utilized for applications in one way sound transmission, noise control, isolators, circulators and energy harvesting.

This paper focuses on improving speckle reduction and denoising performance in ultrasound images by leveraging neural networks. A dataset of simulated ultrasound images was created using Field-II simulation software based on CT scan images, to create clean and noisy image pairs. Various Convolutional Neural Network models based on U-Net and generative adversarial networks were developed and tested. Peak Signal-to-Noise-Ratio (PSNR) and Structural Similarity Index Measurement (SSIM) were used as metrics along with qualitative assessment. Results show that our tuned U-Net generator network outperformed traditional filtering such as Lee and BM3D.

Although the drug-eluting stent (DES) has dramatically reduced the rate of coronary restenosis, it still occurs in up to 20% of patients with a DES. Monitoring drug delivery could be one way to decrease restenosis rates. We demonstrate real-time photoacoustic imaging and spectroscopy (PAIS) using a wavelength-tunable visible laser and clinical ultrasound scanner to track cardiac drug delivery. The photoacoustic signal was initially calibrated using porcine myocardial samples soaked with a known concentration of a drug surrogate (Dil). Next, an in situ coronary artery was perfused with DiI for 20 min and imaged to monitor dye transport in the tissue. Finally, a partially DiI-coated stent was inserted into the porcine brachiocephalic trunk for imaging. The photoacoustic signal was proportional to the DiI concentration between 2.4 and 120 mu g/ml, and the dye was detected over 1.5 mm from the targeted coronary vessel. Photoacoustic imaging was also able to differentiate the DiI-coated portion of the stent from the uncoated region. These results suggest that PAIS can track drug delivery to cardiac tissue and detect drugs loaded onto a stent with sub-mm precision. Future work using PAIS may help improve DES design and reduce the probability of restenosis. (C) 2017 Society of Photo-Optical Instrumentation Engineers (SPIE)

A caracterização de tecido ósseo por ultra-som para o diagnóstico de osteoporose tem sido investigada como uma alternativa a densitometria óssea baseada em radiação ionizante. A interação do ultra-som com o tecido ósseo é fundamentalmente diferente da que ocorre com a energia ionizante. O potencial da técnica ultra-sônica baseia-se nos efeitos sobre a propagação do campo acústico causados pela estrutura, composição e massa do tecido que está sendo investigado. Quatro estudos in-vitro e um estudo clínico estão descritos neste trabalho. O primeiro estudo in-vitro compara a correlação entre medidas ultra-sônicas e de densidade mineral óssea (em g/cm3) em tecido trabecular humano e bovino. A velocidade e atenuação ultra-sônicas em amostras ósseas foram determinadas pela técnica de inserção convencional (modo de transmissão) e a medida de densidade mineral óssea foi realizada por absortometria de um fóton (SPA). O mecanismo de interação do ultra-som com osso trabecular é pouco conhecido. O segundo estudo in-vitro investigou como a presença da medula óssea afeta as medidas de velocidade e atenuação. As correlações entre medidas ultrasônicas e de densidade mineral óssea (em g/cm3) por SPA, com e sem a presença da medula óssea, são também determinadas. A medida ultra-sônica de inserção convencional é comparada a medida de inserção por contato. O terceiro estudo in-vitro investigou em amostras de calcâneo as correlações entre medidas ultra-sônicas e de densidade mineral óssea (em g/cm3 e em g/cm2) por SPA. A determinação da densidade mineral Óssea em g/cm2 (BMD) a partir de medidas ultra-sônicas nas amostras foi pela primeira vez investigada, utilizando-se uma técnica de regressão linear univariável e multivariável e uma técnica multivariável não-linear baseada em redes neurais. Um novo parâmetro, baseado na média da frequência instantânea (MIF) do sinal da amostra e de referência, foi proposto para caracterizar o tecido ósseo devido a sua alta correlação com a atenuação. O efeito das corticais ósseas do calcâneo nas medidas ultra-sônicas é pouco conhecido. O quarto estudo in-vitro determinou a correlação entre medidas ultrasônicas e de densidade mineral óssea (em g/cm3) por SPA, com e sem a presença das corticais ósseas. Finalmente, no estudo clínico foram determinadas as correlações entre medidas ultra-sônicas no calcanhar e de densidade mineral óssea por DEXA (em g/cm2) no cólo femoral. A determinação da densidade óssea a partir de medidas ultra-sônicas no calcanhar foi pela primeira vez investigada, utilizando-se uma técnica de regressão linear univariável e multivariável e uma técnica multivariável não-linear baseada em redes neurais. / Ultrasonic assessment of bone for managing osteoporosis has been investigated as an alternative to radition-based bone densitometry technology. In contrast with the ionizing electromagnetic radiation of such clinical bone densitometric technique, ultrasound is a mechanical wave and thus interacts with bone in a fundamentally distinct manner. Ultrasound is viewed as having great potential for assessing bone since its propagation is affected by the structure, composition, and mass of the bone tissue being interrogated. Four in-vitro and one clinical study are reported in this work. In the first in-vitro study a comparison is reported on the ultrasonic assessment of human trabecular and bovine trabecular bone samples. Both ultrasonic velocity and attenuation were evaluated through a standard transmission insertion technique and correlated with bone mineral density (in g/cm3 ) as determined with single photon absorptiometry (SPA). There is a relatively limited understanding of how ultrasound interacts with cancellous bone. One potentially model leads analytically to the demonstration that ultrasound propagation through bone is dependent on several factors, including the properties of the fluid, which saturates the pores of the cancellous bone tissue. The second in-vitro study was carried out to assess how the presence of marrow affects the velocity and attenuation measurements. The correlation between ultrasonic and densitometric measurements (in g/cm3) by SPA, with and without the bone marrow, are also determined. A second part of this study compared the measurements of ultrasonic attenuation and velocity on bovine cancellous bone samples using a standard insertion technique with those obtained using a contac method. The thrid in-vitro study with the calcis trabecular samples investigated the correlations between ultrasonic measurements and bone mineral density (in g/cm3 e em g/cm2) as measured by SPA. A nonlinear multivariate estimation technique based on neural network was the first time investigated to determine the ability of ultrasonic measurements to estimate bone mineral density in g/cm2 (BMD). A linear univariate and multivariate estimation of BMD was compared with the neural network approach. A new parameter to characterize the trabecular bone is been proposed, which is based on the mean instantaneous frequency (MIF) of the sample and reference signals after transmission through the os calcis. It was founded a high correlation between MIF and the attenuation (BUA). Little is known about the effect of the os calcis cortical shell on ultrasonic measurements. The fourth in-vitro study with os calcis samples determined the correlation between ultrasonic and densitometric measurements (in g/cm3) by SPA with and without the cortical shell. Finally, a nonlinear multivariate estimation technique based on neural network was the first time investigated to determine the ability of clinical ultrasonic measurements in the heel to estimate bone mineral density (BMD) in the femoral neck. A linear univariate and multivariate estimation to predict BMD in patients is also compared with the neural network approach.

A level set-based segmentation procedure has been implemented to identify target object boundaries from 3D medical ultrasound images. Several test images (simulated, scanned phantoms, clinical) were subjected to various preprocessing methods and segmented. Two metrics of segmentation accuracy were used to compare the segmentation results to ground truth models and determine which preprocessing methods resulted in the best segmentations. It was found that by using an anisotropic diffusion filtering method to reduce speckle type noise with a 3D active contour segmentation routine using the level set method resulted in semi-automated segmentation on par with medical doctors hand-outlining the same images.