Effects of gas pockets on high-intensity focused ultrasound field

The paper describes experimental and numerical studies of the effects of gas pockets on a high-intensity focused ultrasound (HIFU) field. Air bubbles ranging from 0.8 to 2.4 mm in radius were produced in transparent polyacrylamide tissue-mimicking gels. A single-element 3.5-MHz HIFU transducer was used to sonicate the gel phantoms. The changes in the HIFU beam pattern for air bubbles at different positions were visualized by the Schlieren method. Quantitative measurements of pressure at the HIFU focus by a calibrated needle hydrophone showed considerable reduction in the focal pressure with the presence of an air pocket. The presence of a single 1.2-mm-radius air bubble, at a 5 mm axial pre-focal position, reduced the focal intensity by 50% and increased the lateral focal dimension by 50%. For air bubbles at pre-focal position close to the focus, lesion formation was observed not at the theoretical focus, but in front of the air bubble and the air bubble became a barrier for the post-focal ultrasound propagation. The effects of reflection were simulated numerically and were compared with the experiments. The results can be used as guidelines for evaluation of potential safety concerns produced by trapped gas-pockets in various HIFU therapies.     

Design and characterization of dual-curvature 1.5-dimensional high-intensity focused ultrasound phased-array transducer

A dual-curvature focused ultrasound phased-array transducer with a symmetric control has been developed for noninvasive ablative treatment of tumors. The 1.5-D array was constructed in-house and the electro-acoustic conversion efficiency was measured to be approximately 65%. In vitro experiments demonstrated that the array uses 256 independent elements to achieve 2-D wide-range high-intensity electronic focusing.     

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm2 for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.     

Numerical study of a simple transcranial focused ultrasound system applied to blood-brain barrier opening

In this paper, we investigate the focalization properties of single-element transducers at low frequencies (300 to 1000 kHz) through primate and human skulls. The study addresses the transcranial targeting involved in ultrasound- induced blood-brain barrier (BBB) opening with clinically relevant targets such as the hippocampus and the basal ganglia, which are typically affected by early Alzheimer's and Parkinson's disease, respectively. A finite-difference, timedomain simulation platform is used to solve the 3-D linear acoustic wave equation with CT-based acoustic maps of the skulls. The targeted brain structures were extracted from 3-D brain atlases registered with the skulls and used to virtually position and orient the transducers. The effect of frequency is first investigated and the targeting of the different structures is then tested. The frequency of 500 kHz provided the best tradeoff between phase aberrations and standing wave effects in the human case, whereas the frequency of 800 kHz was most suitable in the case of the primate skull. A fast periodic linear chirp method was developed and found capable of reducing the standing wave effects. Such a simple, affordable, and convenient system is concluded to be feasible for BBB opening in primates and humans and could thus allow for its broader impact and applications.     

Numerical simulations of heating patterns and tissue temperature response due to high-intensity focused ultrasound

The results of this paper show-for an existing high intensity, focused ultrasound (HIFU) transducer-the importance of nonlinear effects on the space/time properties of wave propagation and heat generation in perfused liver models when a blood vessel also might be present. These simulations are based on the nonlinear parabolic equation for sound propagation and the bio-heat equation for temperature generation. The use of high initial pressure in HIFU transducers in combination with the physical characteristics of biological tissue induces shock formation during the propagation of a therapeutic ultrasound wave. The induced shock directly affects the rate at which heat is absorbed by tissue at the focus without significant influence on the magnitude and spatial distribution of the energy being delivered. When shocks form close to the focus, nonlinear enhancement of heating is confined in a small region around the focus and generates a higher localized thermal impact on the tissue than that predicted by linear theory. The presence of a blood vessel changes the spatial distribution of both the heating rate and temperature.     

Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer

Pulsed high-intensity focused ultrasound (pHIFU) uses acoustic pressure to physically disrupt tumours. The aim of this study was to investigate whether pHIFU can be used in combination with immune checkpoint inhibitors (ICIs) to enhance survival of tumour-bearing animals. Murine orthotopic pancreatic KPC tumours were exposed both to a grid of pHIFU lesions (peak negative pressure = 17 MPa, frequency = 1.5 MHz, duty cycle = 1%, 1 pulse s⁻¹, duration = 25 s) and to anti-CTLA-4/anti-PD-1 antibodies. Acoustic cavitation was detected using a weakly focused passive sensor. Tumour dimensions were measured with B-mode ultrasound before treatment and with callipers post-mortem. Immune cell subtypes were quantified with immunohistochemistry and flow cytometry. pHIFU treatment of pancreatic tumours resulted in detectable acoustic cavitation and increased infiltration of CD8⁺ T cells in the tumours of pHIFU and pHIFU + ICI-treated subjects compared with sham-exposed subjects. Survival of subjects treated with pHIFU + ICI was extended relative to both control untreated subjects and those treated with either pHIFU or ICI alone. Subjects treated with pHIFU + ICI had increased levels of CD8⁺IFNγ⁺ T cells, increased ratios of CD8⁺IFNγ⁺ to CD3⁺CD4⁺FoxP3⁺ and CD11b⁺Ly6G⁺ cells, and decreased CD11c^high cells in their tumours compared with controls. These results provide evidence that pHIFU combined with ICI may have potential for use in pancreatic cancer therapy.     

高强度聚焦超声联合全氟戊烷液滴在乳腺癌治疗增效中的实验研究

目的:探讨高强度聚焦超声(High-Intensity Focused Ultrasound,HIFU)联合全氟戊烷液滴(Perfluoropentane droplets,PFP),对小鼠乳腺癌4T1细胞治疗的增效作用。方法:制备PFP,检测其平均粒径及形态结构。试验设立三组:HIFU假照组,单纯HIFU治疗组,HIFU联合PFP治疗组。流式细胞仪检测HIFU分组治疗乳腺癌细胞后细胞存活率及死亡率;体内动物试验分组处理后,二维超声观察HIFU辐照前后肿瘤回声灰度变化情况,超声造影剂灌注缺损面积占总面积百分比评价不同治疗方式对裸鼠皮下移植瘤的消融能力。结果:所制备的PFP平均粒径为1.2μm,形态呈规则球形。细胞试验显示,HIFU联合PFP治疗组乳腺癌细胞死亡率(23.50±1.34)%显著高于单纯HIFU治疗组(14.34±0.55)%和HIFU假照组(11.76±0.62)%(P<0.05);动物试验显示HIFU联合PFP治疗组肿瘤消融面积占总面积百分比(84.03±4.47)%显著高于单纯HIFU治疗组(41.23±4.24)%(P<0.05),HIFU假照组无明显灌注缺损区域。结论:HIFU联合PFP可显著增强对乳腺癌细胞及组织的消融能力。     

In vitro and in vivo brain ablation created by high-intensity focused ultrasound and monitored by MRI

In this paper, magnetic resonance imaging (MRI) is investigated for monitoring small and large lesions created by high-intensity focused ultrasound (HIFU) in freshly excised lamb brain and in rabbit brain in vivo. A single-element spherically focused transducer of 5 cm diameter, focusing at 10 cm and operating at 1 MHz was used. A prototype MRI-compatible positioning device that is used to navigate the transducer is described. The effects of HIFU were investigated using T1-W and T2-W fast spin echo (FSE) and fluid-attenuated inversion recovery (FLAIR). T2-W FSE and FLAIR show better anatomical details within the brain than T1-W FSE, but with T1-W FSE, the contrast between lesion and brain is higher for both thermal and bubbly lesions. The best contrast between lesion and brain with T1-W FSE is obtained with TR above 500 ms, whereas with T2-W FSE, the best contrast is observed between 40 and 60 ms. The maximum contrast to noise ratio (CNR) measured with T1-W FSE was approximately 20. With T2-W FSE, the corresponding CNR was approximately 12. With this system, we were able to create large lesions (by producing overlapping lesions), and it was possible to monitor these lesions with MRI with excellent contrast. The length of the lesions in vivo brain was much higher than the length in vitro, indicating that the penetration in the in vitro brain is limited, possibly by reflection due to trapped bubbles in the blood vessels. This paper demonstrates that HIFU has the potential to treat brain tumors in humans. This could be done either using a single-element transducer with a frequency around 1 MHZ or using a multi-element transducer.     

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from Bmode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimetersized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.     

Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates

In vivo transcranial and noninvasive cavitation detection with blood-brain barrier (BBB) opening in nonhuman primates is hereby reported. The BBB in monkeys was opened transcranically using focused ultrasound (FUS) in conjunction with microbubbles. A passive cavitation detector, confocal with the FUS transducer, was used to identify and monitor the bubble behavior. During sonication, the cavitation spectrum, which was found to be region-, pressure-, and bubble-dependent, provided real-time feedback regarding the opening occurrence and its properties. These findings demonstrate feasibility of transcranial, cavitation-guided BBB opening using FUS and microbubbles in noninvasive human applications.     

聚焦超声的辐射力计算与高强度聚焦超声功率测量实验

研究聚焦超声场的辐射力计算。应用几何声学方法,推导了聚焦超声作用于测试靶上的辐射力通用公式,讨论了全反射靶和全吸收靶上的辐射力。最后给出了应用辐射力法测量高强度聚焦超声装置的声功率的实例,其结果与良热法测得的声功率接近,偏差不大于3%。     

聚焦超声的辐射力计算与高强度聚焦超声功率测量实验

本文研究聚焦超声场的辐射力计算，应用几何声学方法，推导了聚焦超声作用于测试靶上的辐射力的通用公式，讨论全反射靶和全吸收靶上的辐射力，最后给出了应用辐射力法测量高强度聚焦超声装置的声功率的实例，其结果与量热法测量的声功率接近，偏差不大于３％。     

Vagus nerve modulation using focused pulsed ultrasound: Potential applications and preliminary observations in a rat

The use of focused ultrasonic waves to modulate neural structures has gained recent interest due to its potential in treating neurological disorders noninvasively. While several articles have focused on the use of ultrasound neuromodulation on peripheral nerves, none of these studies have been performed on the vagus nerve. We present preliminary observations on the effects of focused pulsed ultrasound (FPUS) on the conduction of the left cervical vagus nerve of a Long Evans rat. Ultrasound energy was applied at a frequency of 1.1 MHz, and at spatial‐peak, temporal average intensities that ranged from 13.6 to 93.4 W/cm². Vagus nerve inhibition was observed in most cases. Results of this preliminary study suggested that there is a proportional relationship between acoustic intensity and the level of nerve inhibition.     

Evaluation of accuracy of a theoretical model for predicting thenecrosed tissue volume during focused ultrasound surgery

The concept of thermal dose as a predictor for the size of the necrosed tissue volume during high-intensity focussed ultrasound surgery was tested. The sensitivity of the predicted lesion size to the uncertainties in the iso-dose constant, attenuation coefficient, and thermal dose threshold of necrosis was studied. The predicted lesion size appears to be independent of attenuation at some high attenuation values and certain depth in tissue. Thus, for a given target depth, a proper selection of frequency could minimize the lesion size variability due to uncertainty in the tissue attenuation. The predicted lesion size was less dependent on the uncertainties in the iso-dose constant and thermal dose of necrosis. The predictions of the model were compared with experimental data in rabbit muscle, and experimental data in cat and rat brain measured by others. The agreement was found to be good in most of the experiments. Similarly, the model was found to predict well the trends of increasing power and pulse duration     

Large improvement of the electrical impedance of imaging and high-intensity focused ultrasound (HIFU) phased arrays using multilayer piezoelectric ceramics coupled in lateral mode

With a change in phased-array configuration from one dimension to two, the electrical impedance of the array elements is substantially increased because of their decreased width (w)-to-thickness (t) ratio. The most common way to compensate for this impedance increase is to employ electrical matching circuits at a high cost of fabrication complexity and effort. In this paper, we introduce a multilayer lateral-mode coupling method for phased-array construction. The direct comparison showed that the electrical impedance of a single-layer transducer driven in thickness mode is 1/(n2(1/(w/t))2) times that of an n-layer lateral mode transducer. A large reduction of the electrical impedance showed the impact and benefit of the lateral-mode coupling method. A one-dimensional linear 32-element 770-kHz imaging array and a 42-element 1.45-MHz high-intensity focused ultrasound (HIFU) phased array were fabricated. The averaged electrical impedances of each element were measured to be 58 Ω at the maximum phase angle of -1.2° for the imaging array and 105 Ω at 0° for the HIFU array. The imaging array had a center frequency of 770 kHz with an averaged -6-dB bandwidth of approximately 52%. For the HIFU array, the averaged maximum surface acoustic intensity was measured to be 32.8 W/cm2 before failure.     

超声阵列换能器设计及声场模拟

聚焦超声采用的聚焦方式有许多种,电子聚焦是其中之一,与其它聚焦方式相比,电子聚焦技术有很多优点,然而一些相互矛盾的条件对其设计有很大影响。通过用快速算法对阵元声场、以及频率对场的影响进行模拟,对阵列设计中的几个主要考虑方面进行了分析,提供了一般设计思路。采用伪逆矩阵算法,对变迹技术和多焦点技术进行计算机模拟,为焦域控制提供了新的思路,结果表明：将电子聚焦阵列换能器用于高强度聚焦超声治疗设备,比其它     

Development of a mathematical model for the effect of temperature and relative humidity on the water vapour permeability of plastic films

The water vapour permeability constants of three flexible films (LDPE, PET and a laminate of both films) were determined at 20, 30 and 40 °C and from 55 to 90% relative humidities. The relationship between permeability and temperature followed the Arrhenius model for the three films. The relative humidity also influenced the permeability of the films. A mathematical model describing permeance (P/X - the permeability of laminates or films) as a function of external relative humidity and temperature was developed. The model can be used to predict the permeance of the three films at different temperatures and relative humidities.     

经颅聚焦超声治疗脑血栓的数值仿真研究

脑卒中是致残和致死的首因,经颅脑卒中治疗具有无创和颅内出血风险低等优势,目前经颅聚焦超声治疗血栓性缺血脑卒中时使用参数尚不明确。基于志愿者头颅CT图像和82阵元相控换能器建立三维数值仿真模型,利用时域有限差分法数值解析Westervelt声波非线性传播方程,对0.5～1.0 MHz超声激励频率和输入声功率等参数进行数值仿真筛选。结果表明：频率相同时焦点处形成的负压越大所需输入声功率越大,经颅所需输入声功率约为开颅的1.5倍;频率越高焦域面积越小但焦域处的旁瓣增多;频率相同时经颅和开颅模型的焦域形状和大小相近但经颅时的旁瓣较强;焦点处负压达到具有溶栓效果的-6 MPa和具有显著溶栓效果的-8 MPa时所需声功率随频率的提高先减少后增加且频率为0.8 MHz时最小;辐照时间和占空比对焦点位置和焦域面积没有影响。     

非侵入式超声塑形及其实现的关键技术

非侵入式超声塑形是最近几年刚刚兴起的技术,使用特殊的换能器产生高能量聚焦超声波作用于人体脂肪层,利用超声波的空化效应破坏脂肪细胞膜,游离的脂肪通过人体代谢系统排除体外,从而达到塑形的目的。此项技术具有安全无创等优点。简要讨论了非侵入式超声塑形的物理机理、工作参数、实际系统的构成和工作原理,重点介绍了其中的两项关键技术：超声塑形系统中的发射换能器和频率跟踪技术的应用。     

Gender focused training and knowledge enhances the adoption of climate resilient seeds

Adoption of any agricultural technology depends upon the way in which farmers are being informed about its benefits. Educational status, caste, gender and other social issues also play a significant role in the adoption process. To evaluate the impact of trainings on quality seed production, access to the climate resilient rice seeds, availability of information about seed sources and use of IRRI super bags, a randomized experimental research was carried out over a period of two years across five different states of India. The baseline and a follow-up survey was conducted to capture the farming practices followed by during wet seasons of 2016 and 2017, respectively. The impact of trainings, seed use, information given and agro-based goods was evaluated by comparing the adoption behaviour of treatment and control farmers. There was an increase (28.8%) in the practice of using salt solution to clean seeds primarily due to the impact of quality seed production (QSP) trainings. Female farmers responded more than the male farmers as number of women adopting the practice was higher than men. The impact of the trainings on farmers' knowledge and adoption of climate resilient/stress tolerant rice varieties (STRV) was also more pronounced on females than on male farmers. Farmers’ access to seeds substantially enhanced the adoption and reusability irrespective of the gender. Similarly, the information delivered to the farmers was quite economical in enhancing the awareness and adoption of climate resilient rice, but the effect was predominantly driven by female farmers. Female farmers performed relatively better with respect to the storing the new seeds in IRRI super bags. Thus, incentivising farmers in general and female farmers in particular can serve as a potential means to adopt agricultural technologies that have potential to boost rural economy and enhance the food security. The results are being supported by a rigorous empirical analysis.