Experimental and Numerical Investigation of Therapeutic Ultrasound Angioplasty

Therapeutic ultrasound angioplasty is an emerging minimally invasive cardiovascular surgical procedure that involves the delivery of ultrasonic displacements to the distal-tip of small diameter wire waveguides. The ultrasonic distal-tip displacements affect atherosclerotic plaque and thrombus by direct contact ablation, pressure wave components and cavitation, in addition to an acoustic streaming event around the distal-tip. This study uses experimental and numerical methods to investigate ultrasonic displacements in wire waveguides and the effect the distal-tip displacements have on the surrounding fluid. An experimental therapeutic ultrasound wire waveguide apparatus is described that delivers displacements to the distal-tip of 1.0 mm and tapered 0.35 mm diameter nickel-titanium (NiTi) waveguides. The operating frequency of the apparatus has been experimentally determined to be 23.5 kHz and for the power settings tested delivers displacements of up to 85 µm peak-to-peak (p-p) to the distal-tip of 1.0 mm diameter waveguides. The apparatus has been shown to directly ablate calcified materials with a stiffer response when compared with atherosclerotic plaques and to generate cavitation and acoustic streaming. A coupled fluid-structure numerical model of the waveguide and fluid surrounding the distal-tip has been developed that predicts the waveguide displacements and stresses along the entire length of the wire waveguide. The structural results of the model have been validated against experimental measurements of the displacements of the waveguide with the inclusion of a constant damping value of 4.5%. The fluid results of the model predict the pressure amplitudes developed in the surrounding fluid and compare closely with values reported in literature. The model predicts the distal-tip displacements required to cause cavitation, a major disruptive event, and has been compared with experimental observations made with the ultrasonic wire waveguide apparatus. The waveguide numerical model will prove a valuable design tool in the further development and improvement of this emerging cardiovascular technology

A Numerical Acoustic Fluid-structure Model of a Therapeutic Ultrasound Angioplasty Device

Ultrasonic angioplasty involves the use of ultrasonic vibrations delivered to the distal-tip of small diameter wire waveguides and is an emerging technology the may have potential use in the treatment of complicated atherosclerotic plaques during cardiovascular surgery. Complicated plaques, including chronic total occlusions and calcified lesions, seriously reduce success rates during standard intervention involving guidewire access, followed by balloon dilation or stent delivery. The large amplitude (0-150 μm) wire waveguide distal-tip displacements in the low-frequency ultrasonic (18-45 kHz) range have been shown to disrupt plaque material by direct contact ablation and cavitation, acoustic streaming and pressure wave components in adjacent fluid 1. The effects on this surrounding fluid are complex and are related to the distal-tip geometry, frequency of operation, vibration amplitude, as well as the operating environment, including, fluid properties and boundary conditions. While the majority of work to date on ultrasound angioplasty has focused on experimental and clinical studies 2, 3, further understanding of distal-tip effects is necessary. This work describes a numerical fluid-structure model of the wire waveguide distal-tip and is used to predict the pressures developed in the fluid region near the tip wall, the acoustic pressure field and, with the inclusion of appropriate threshold intensity, when cavitation will occur. The model has been validated against experimental acoustic pressure field results reported in the literature. The model can be further used to predict the effects of parameters such as distal-tip geometry, displacement amplitude and frequency of operation and will prove a valuable design aid in the choice of optimum powers to disrupt various biological materials

The impact of SARS-CoV-2 on the mental health of healthcare workers in a hospital setting—A Systematic Review

Objectives The SARS-CoV-2 global pandemic has subjected healthcare workers (HCWs) to high risk of infection through direct workplace exposure, coupled with increased workload and psychological stress. This review aims to determine the impact of SARS-CoV-2 on mental health outcomes of hospital-based HCWs and formulate recommendations for future action. Methods A systematic review was performed between 31st December 2019 and 17th June 2020 through Ovid Medline and Embase databases (PROSPERO ID CRD42020181204). Studies were included for review if they investigated the impact of SARS-CoV-2 on mental health outcomes of hospital-based HCWs and used validated psychiatric scoring tools. Prevalence of ICD-10 classified psychiatric disorders was the primary outcome measure. Results The initial search returned 436 articles. Forty-four studies were included in final analysis, with a total of 69,499 subjects. Prevalence ranges of six mental health outcomes were identified: depression 13.5%-44.7%; anxiety 12.3%-35.6%; acute stress reaction 5.2%-32.9%; post-traumatic stress disorder 7.4%-37.4%; insomnia 33.8%-36.1%; and occupational burnout 3.1%-43.0%. Direct exposure to SARS-CoV-2 patients was the most common risk factor identified for all mental health outcomes except occupational burnout. Nurses, frontline HCWs, and HCWs with low social support and fewer years of working experience reported the worst outcomes. Conclusion The SARS-CoV-2 pandemic has significantly impacted the mental health of HCWs. Frontline staff demonstrate worse mental health outcomes. Hospitals should be staffed to meet service provision requirements and to mitigate the impact onmental health. This can be improved with access to rapid-response psychiatric teams and should be continually monitored throughout the pandemic and beyond its conclusion

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5.01; HR, 1.71; P,.001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5.002, and HR, 1.47; P,.001), as was overall survival (HR, 1.32; P,.001, and HR, 1.45; P,.001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease

A Numerical Acoustic Fluid-structure Simulation of Therapeutic Ultrasound Angioplasty

INTRODUCTION Therapeutic ultrasound angioplasty is the delivery of high amplitude ultrasonic displacements to the distal-tip of small diameter wire waveguides with the goal of disrupting atherosclerotic plaques. This is a minimally invasive procedure that may have potential\u27 in the treatment of complicated chronic total occlusions. The disruption of plaque is due to direct contact ablation and also cavitation, pressure waves and acoustic streaming in the fluid surrounding the vibrating waveguide distal-tip [1]. Cavitation appears to play a major role and some authors have suggested that plaque ablation is only evident above the cavitation threshold [2]. Makin and Everbach [3] performed experimental measurements of the acoustic pressures in the field surrounding a vibrating wire waveguide distal-tip (frequency = 22.5 kHz, displacement amplitude = 651lm, tip diameter = 2.46mm). The measured acoustic pressures in the region ahead of the distal-tip are shown in Figure I. No measurements could be made in the region close to the tip but the authors concluded that these pressures would be sufficient to cause the cavitation that was observed, based on the trend in Figure I. This work describes a numerical acoustic fluidstructure model of the wire waveguide and fluid surrounding the distal-tip. The model will predict wire waveguide behaviour to a prescribed ultrasonic input displacement and will predict pressures developed around the distal-tip. METHODS An axisymmetric numerical model of the wire waveguide and fluid surrounding the distal-tip based on the device description by Makin and Everbach [3] was developed in ANSYS©. The model consisted of both structural elements (Plane42) for the waveguide and acoustic elements (Fluid29) for the fluid. A tluidstructure interface was placed at element couplings and infinite acoustic boundary elements (Fluid 129) defined the extremities of the model preventing acoustic reflection RESULTS A comparison of the experimental [3] and the numerical results are shown in Figure l. A close comparison is achieved and, in addition, the numerical model can predict pressures at the fluid-structure interface. With the inclusion of a cavitation threshold (CT), displacements and frequencies required to cause cavitation can be predicted. CONCLUSION The validated model can be used to investigate the effects of changing device parameters such as frequency of operation, displacement amplitudes and geometry, on both waveguide structural response (displacements and stresses) and pressures developed in the surrounding fluid

Development and Performance Characteristics of an Ultrasound Angioplasty Device

INTRODUCTION The effect of atherosclerosis is well documented and many procedures such as balloon angioplasty and stentimplantation have been developed to reopen occluded arteries. However, there are considerable differences in the material properties of various atherosclerotic lesions as they develop. Many authors have suggested that rigid calcified plaques may require specific procedures that target this rigid material through de-bulking or complete removal (Salunke et al, 1997). Ultrasound angioplasty is the delivery of high power low frequency ultrasound via a wire waveguide to the lesion location. This results in distal tip wire displacements of up to 100um peak-to-peak (p-p) at frequencies of between 20-45 kHz (Atar, 1999 and Yock, 1997). Ultrasound angioplasty was shown to be effective in the ablation of fibrous and calcified blockages in arteries (Siegel, 1993). At the displacements and frequencies mentioned the pressure field developed can produce disruptive cavitations around the distal tip (Gavin et al, 2004). The principal objective of this study was to develop an ultrasound angioplasty device and investigate its performance characteristics both experimentally and numerically. MATERIALS AND METHODS Ultrasound was generated by a piezoelectric transducer driven by an ultrasonic generator. The ultrasonic generator drives the transducer at its resonant frequency, in the case of the present device, 22.5 kHz with output displacements of between 3-18 um (p-p). This output was passed into an acoustic horn with a wire waveguide attached to the distal end. These amplify the displacement characteristics and the waveguide has a working flexibility similar to present balloon catheters and a working length of approximately 500mm. The wire waveguide was ensheathed in a catheter with the distal end of the wire protruding at the tip. The output (p-p) displacements at the distal end of the wire waveguide were measured using an optical microscope with video acquisition and measurement. The characteristics of the system along the length of the wire waveguide have also been numerically simulated using FEA RESULTS The output displacement characteristics of the wire waveguide showed achievable peak-to-peak output displacements of 15- 90 um (p-p) at 22.5 kHz. Fig. 1 shows an image obtained by the optical measurement system of the distal tip of a 1mm wire waveguide subjected to ultrasonic energy. DISCUSSION This initial testing of tip displacements has proved promising and the comparison of the FEA and experimental results has shown good agreement. Future studies involve identifying cavitations and testing is to be carried out on various materials that simulate plaque with a focus on rigid calcified lesions

Pressure Distribution around Spherical Distal Ball-tip in Ultrasound Angioplasty

INTRODUCTION Ultrasound Angioplasty has been shown to be effective in the removal and re-canalising of blockages in arteries (Siegel RJ, 1993). By delivering therapeutic ultrasound to the blockage, via a wire waveguide to a ball-tip, the lesion or thrombus is affected by pressure waves, micro streaming, cavitation and direct contact with the oscillating ball-tip. Most work to date has concentrated on a spherical ball-tip geometry at the distal end of the wire waveguide (Steffen, 1994 and Rosenschein, 1996). Tip displacements usually lie between 10 - 100m (peak-to peak) and ball tip diameters between 1 - 2mm (Atar, 1999 and Yock, 1997). The analytical solution of an oscillating sphere is given in Equation 1 and has previously been used to describe pressures in ultrasound angioplasty (Siegel, 1996). METHODS To simulate the interaction between the ball-tip and surrounding fluid a Finite Element Acoustic Model using fluid-solid interaction and acoustic elements was developed. The displacement and frequency were the input loads on the solid ball tip, while outputs included maximum nodal pressures at points in the acoustic field. From this numerical solution a comparison was performed with the analytical solution to validate the model. DISCUSSION The correspondence between the finite element solution and the analytical solution for an oscillating sphere is shown in Figure 1. This is a plot of the maximum pressures at points axially parallel to the tip at a distance of 1mm. This location is similar to that of the arterial wall, although the presence of the wall is ignored here. Areas of cavitation activity may be identified where the maximum pressure amplitude exceeds ambient fluid pressure. This information may aid in the design of the devices such as desirable ball-tip size, geometry and exposure time. In future work the validated model will be used to solve the pressure distribution around more complex geometries to determine possible advantages in the use of non-spherical ball-tips

Facile and efficient one-pot synthesis of 2-arylbenzoxazoles using hydrogen tetrachloroaurate as catalyst under oxygen atmosphere*

In this paper, we presented a novel method for the facile and efficient one-pot synthesis of 2-arylbenzoxazoles, which were directly synthesized from 2-aminophenol and aldehydes catalyzed by hydrogen tetrachloroaurate (HAuCl4·4H2O) under an oxygen atmosphere with anhydrous tetrahydrofuran (THF) as solvent or in solvent-free condition. The results show that this method could bring excellent yields as high as 96%. THF was proven to be the best choice among several solvents screened and the reaction was tolerated with a variety of aromatic aldehydes possessing electron-donating or withdrawing groups. The advantages of the present method lie in catalytic process using economic and environmentally benign dioxygen as oxidant