High speed imaging of bubble clouds generated in pulsed ultrasound cavitational therapy--histotripsy

Our recent studies have demonstrated that mechanical fractionation of tissue structure with sharply demarcated boundaries can be achieved using short (< 20 micros), high intensity ultrasound pulses delivered at low duty cycles. We have called this technique histotripsy. Histotripsy has potential clinical applications where noninvasive tissue fractionation and/or tissue removal are desired. The primary mechanism of histotripsy is thought to be acoustic cavitation, which is supported by a temporally changing acoustic backscatter observed during the histotripsy process. In this paper, a fast-gated digital camera was used to image the hypothesized cavitating bubble cloud generated by histotripsy pulses. The bubble cloud was produced at a tissue-water interface and inside an optically transparent gelatin phantom which mimics bulk tissue. The imaging shows the following: (1) Initiation of a temporally changing acoustic backscatter was due to the formation of a bubble cloud; (2) The pressure threshold to generate a bubble cloud was lower at a tissue-fluid interface than inside bulk tissue; and (3) at higher pulse pressure, the bubble cloud lasted longer and grew larger. The results add further support to the hypothesis that the histotripsy process is due to a cavitating bubble cloud and may provide insight into the sharp boundaries of histotripsy lesions.     

Spatial variability in acoustic backscatter as an indicator of tissue homogenate production in pulsed cavitational ultrasound therapy

Spatial variability in acoustic backscatter is investigated as a potential feedback metric for assessment of lesion morphology during cavitation-mediated mechanical tissue disruption ("histotripsy"). A 750-kHz annular array was aligned confocally with a 4.5 MHz passive backscatter receiver during ex vivo insonation of porcine myocardium. Various exposure conditions were used to elicit a range of damage morphologies and backscatter characteristics [pulse duration = 14 micros, pulse repetition frequency (PRF) = 0.07-3.1 kHz, average I(SPPA) = 22-44 kW/cm2]. Variability in backscatter spatial localization was quantified by tracking the lag required to achieve peak correlation between sequential RF A-lines received. Mean spatial variability was observed to be significantly higher when damage morphology consisted of mechanically disrupted tissue homogenate versus mechanically intact coagulation necrosis (2.35 +/- 1.59 mm versus 0.067 +/- 0.054 mm, p < 0.025). Statistics from these variability distributions were used as the basis for selecting a threshold variability level to identify the onset of homogenate formation via an abrupt, sustained increase in spatially dynamic backscatter activity. Specific indices indicative of the state of the homogenization process were quantified as a function of acoustic input conditions. The prevalence of backscatter spatial variability was observed to scale with the amount of homogenate produced for various PRFs and acoustic intensities.     

Imaging feedback of histotripsy treatments using ultrasound shear wave elastography

Histotripsy is a cavitation-based ultrasound therapy that mechanically fractionates soft solid tissues into fluid-like homogenates. This paper investigates the feasibility of imaging the tissue elasticity change during the histotripsy process as a tool to provide feedback for the treatments. The treatments were performed on agar tissue phantoms and ex vivo kidneys using 3-cycle ultrasound pulses delivered by a 750-kHz therapeutic array at peak negative/positive pressure of 17/108 MPa and a repetition rate of 50 Hz. Lesions with different degrees of damage were created with increasing numbers of therapy pulses from 0 to 2000 pulses per treatment location. The elasticity of the lesions was measured with ultrasound shear wave elastography, in which a quasi-planar shear wave was induced by acoustic radiation force generated by the therapeutic array, and tracked with ultrasound imaging at 3000 frames per second. Based on the shear wave velocity calculated from the sequentially captured frames, the Young's modulus was reconstructed. Results showed that the lesions were more easily identified on the shear wave velocity images than on B-mode images. As the number of therapy pulses increased from 0 to 2000 pulses/location, the Young's modulus decreased exponentially from 22.1 ± 2.7 to 2.1 ± 1.1 kPa in the tissue phantoms (R2 = 0.99, N = 9 each), and from 33.0 ± 7.1 to 4.0 ± 2.5 kPa in the ex vivo kidneys (R2 = 0.99, N = 8 each). Correspondingly, the tissues transformed from completely intact to completely fractionated as examined via histology. A good correlation existed between the lesions' Young's modulus and the degree of tissue fractionation as examined with the percentage of remaining structurally intact cell nuclei (R2 = 0.91, N = 8 each). These results indicate that lesions produced by histotripsy can be detected with high sensitivity using shear wave elastography. Because the decrease in the tissue elasticity corresponded well with the morphological and histological change, this study provides a basis for predicting the local treatment outcomes from tissue elasticity change.     

Exposimetry of unfocused pulsed ultrasound

Therapeutic applications of unfocused pulsed ultrasound have recently been identified and require specialized exposimetry. Spatial distributions of pressure and several measures of intensity are presented for an unfocused pulsed ultrasound field produced by a PZT-4 transducer with diameter 3.8 cm and center frequency 2 MHz. Distributions of pressure I_tp and I_m were adequately uniform over a 4-cm² area in a transverse plane at an axial distance of 7 cm, but not so for I_ta and I_pa , which both exhibited off-axis asymmetric maxima     

脉冲钨离子注入导致的空洞效应

采用由金属蒸汽真空弧(metalvaporvacuumarc,简称MEVVA)离子源引出的强束流脉冲钨离子对H13钢进行了离子注入表面改性研究。在注入剂量为1×1017cm-2,温度为200℃以下,观察到强束流脉冲钨离子注入导致的空洞和空洞的硬化及脆化效应,分析了空洞对注入钨元素浓度深度分布的影响,基于热峰效应(spike),讨论了空洞的形成原因及其与材料耐磨性的关系。     

一种基于气泡群的低频主动声呐目标模拟器设计

为了在水声测试过程中提供尺寸小、成本低、应用灵活、低频和高目标强度的目标模拟器,文中根据水中气泡群具有强散射这一特性,提出了一种面向主动声呐试验的气泡群模拟器设计方法。基于等效介质理论 (EffectiveMedium Theory, EMT)建立了气泡群声散射模型。首先将气泡群划分成立方体网格,然后应用图像处理方法获取立方体网格内气泡群的尺寸分布函数,接着使用 EMT 计算了每个立方体网格中的声反射系数和声波入射到立方体网格中产生的衰减,最后利用声波叠加原理计算了模拟器的反向散射目标强度。不同参数下的数值分析结果表明,气泡群尺寸分布函数呈伽马分布时,目标强度较高;目标强度随着尺寸分布区间减小和孔隙率增大而变大;共振频率随孔隙率增大而降低。结合气泡群孔隙率分布模型,文中给出了一组在低频时具有较高目标强度的小尺寸模拟器设计参数,可供相关设计者参考。     

超声治癌研究

文章简要回顾声声治癌的发展和作者20年来相关的研究。阐明超声高热治疗（UHT）和高强度聚焦超声（HIFU）的原理、方法、仪器和治疗机理，重点论述关于凹球面多元相控阵（CSSMEPA）高热和高强度聚焦超声（HIPFU）治癌机的首创和发展。     

Boundary element analysis of the droplet dynamics induced by spark-generated bubble

Spark bubble droplet generation (SBDG) method is the most recently developed drop-on-demand droplet generation technique where the oscillation of a spark-generated bubble near a circular aperture causes a single droplet quite smaller than the aperture to form and break off. This paper investigates the fluid dynamics of the droplet generated through a flat plate aperture as well as through the nozzle of an axisymmetric chamber using boundary element method and high-speed photography. The results revealed that the bottom wall of the chamber would strongly influence the behavior of the bubble oscillating inside. In addition, it was found that with the same normalized nozzle size and bubble distance from air–liquid interface, a relatively smaller and faster droplet is generated from the chamber nozzle as compared with that formed through the flat plate aperture. Furthermore, although the droplet size decreases, its pinch-off time was found to increase by increasing the size of chamber feeder canal.     

Degradation processes in the aluminum-silicon system induced by pulsed electric signals

Thermal conditions in a metallization layer deposited onto a single crystal silicon substrate were studied during the passage of single electric pulses with a current density of j=(1–8)×10¹⁰ A/m² and a duration of τ=50–800 μs. Mechanisms of the irreversible degradation in the aluminum-silicon contact under the pulsed current action are established. The degradation is manifested by the contact melting and the metallization layer fusion. Methods for the identification of these phenomena and determination of the critical current densities j _k are proposed. The critical current density depends on the current pulse duration as described by the relationship $j_k \sim 1/\sqrt[4]{\tau }$ . It is established that the passage of single current pulses with j≥5×10¹⁰ A/m² and τ≥200 μs leads to the formation of linear defects in the region of maximum temperature gradient in the test structure.     

Nonequilibrium solidification effects induced by a pulsed magnetic field in ionic crystals

A digital DTA study of the process of solidification in KCl pretreated in a weak pulsed magnetic field (PMF) reveals a latent decrease in the enthalpy of solidification, followed by recovery of the initial state 144 h after the treatment. A sharp drop in the enthalpy of solidification observed 72 h after the PMF treatment gives rise to an additional relaxation process (postsolidification effect) revealed by a long-term fluctuational evolution of dissipated heat. According to the X-ray diffraction data, the PMF action upon KCl induces an intracrystalline transformation manifested by a small decrease in the lattice parameter and a sharp increase in the reflection intensity.     

In vitro detection of cavitation induced by a diagnostic ultrasound system

Experiments were performed to determine whether a clinical diagnostic scanner, a Hewlett-Packard (HP) 77020A, could produce cavitation in water containing suspensions of either 0.245-mum polystyrene spheres or Albunex, 1-10 mum albumin-coated microbubbles. Two calibrated, phased-array HP imaging transducers with 2.5- and 5.0-MHz operating frequencies were driven in M-mode (single cycle) and Doppler mode 4 cycles by the HP imaging system. Cavitation was detected in the water with polystyrene spheres at 2.5 MHz in both M-mode and Doppler mode at a peak negative acoustic pressure of 1.1 MPa or greater. Insonification at 5.0 MHz in either mode did not produce a detectable amount of cavitation, even with peak negative pressures as high as 1.2 MPa. Cavitation was not detected in water with the Albunex spheres at either frequency.     

Diagnostics of degradation processes induced by pulsed electric signals at the aluminum-silicon interface

Thermal conditions in an aluminum metallization stripe deposited onto a single crystal silicon substrate have been studied during the passage of single rectangular electric pulse with a current density of j < 8 × 10¹⁰ A/m² and a duration of τ = 100–1000 μs. Based on the results of this analysis, a method of diagnostics of the state of metallization contact systems and determination of the conditions of their safe operation is proposed.     

高强度聚焦超声损伤兔肌肉组织的超声影像学变化的初步研究

探讨高强度聚焦超声损伤兔肌肉组织的超声图像变化。采用高强度聚焦超声经皮照射20只新西兰大白兔双侧后肢肌肉,其中18只于照射前1d、照射后10min、照射后1d,3d,7d,14d,21d,28d进行二维超声、彩色多普勒和能量多普勒超声检查,并于照射后28天处死后测量凝固灶大小。另2只分别于照射后1d及照射后50d解剖,行病理学检查。(1)HIFU照射后凝固灶外周可见强回声带至低回声带的演变过程。(2)HIFU照射后第1d,测量的凝固灶体积最大(1476.59±308.64mm3),第3d～第21d,凝固灶体积逐渐缩小(612.47±127.98mm3)。第28d凝固灶体积最小(343.29±54.79mm3)。超声检查在兔肌肉组织HIFU照射后的随访中发挥了重要的作用,为监测HIFU治疗人体软组织肿瘤超声图像的变化提供了实验依据。     

Shear stress induced by a gas bubble pulsating in an ultrasonic field near a wall

Some of the effects that therapeutic ultrasound has in medicine and biology may be associated with steady oscillations of gas bubbles in liquid, very close to tissue surface. The bubble oscillations induce on the surface steady shear stress attributed to microstreaming. A mathematical simulation of the problem for both free and capsulated bubbles, known as contrast agents, is presented here. The simulation is based on a solution of Laplace's equation for potential flow and existing models for microstreaming. The solution for potential flow was obtained numerically using a boundary integral method. The solution provides the evolution of the bubble shape, the distribution of the velocity potential on the surface, and the shear stress along the surface. The simulation shows that significant shear stresses develop on the surface when the bubble bounces near the tissue surface. In this case, pressure amplitude of 20 kPa generates maximal steady shear stress of several kilo Pascal. Substantial shear stress on the tissue surface takes place inside a circular zone with a radius about half of the bubble radius. The predicted shear stress is greater than stress that causes hemolysis in blood and several orders of magnitude greater than the physiological stress induced on the vessel wall by the flowing blood.     

Acousto-optical effect induced by ultrasound pulses in a nematic liquid-crystal film

The reorientation of the director of a homeotropically aligned nematic liquid-crystal film subjected to ultrasound pulses is discussed. The relationship is investigated for the first time, to our knowledge, between the transmitted optical power and the high-frequency (approximately megahertz) pulsed ultrasound intensity. It is evident that there exists a power law governing the ultrasound-intensity-dependent optical transmission. However, the data indicate no existence of a characteristic threshold for the acousto-optical effect. Our results suggest that acoustic streaming, known to be responsible for acousto-optical effects in cw ultrasound experiments, should also play a similarly important role in the case involving a pulsed ultrasound field.     

超微细气泡水体修复技术

随着科学技术发展的日新月异,水污染问题越来越严重.如何解决水污染问题已经成为社会关注的焦点.超微细气泡水体修复技术在国际上是属于最前沿科技.本工作对超微细气泡水体修复技术的机理等进行了研究并利用日本的超微细气泡曝气机进行了实验研究,结果表明该技术能很好的提高水中的溶解氧并有效的消解底泥有机物,减低底泥厚度,实现水体的修复.     

Synthesis of strained SiGe on Si(100) by pulsed laser induced epitaxy

Pulsed laser induced epitaxy (PLIE), based on melting/solidification processes induced by nanosecond laser pulses, is used to synthesize pseudomorphic Si_1 − xGe_x epilayers from 20 to 80 nm thick Ge layers evaporated on a Si(100) wafer. Ge concentration and strain are characterized by transient reflectivity, energy dispersive X-ray analysis and X-ray diffraction from symmetric (004) and asymmetric (224) reflections. For a low Ge thickness or a high laser fluence, PLIE builds up only a pseudomorphic strained Si_1 − xGe_x layer with a graded Ge composition reaching x ≈ 19% near the surface. When the Ge amount is in excess to achieve this situation, PLIE forms additionally a relaxed Si_1 − xGe_x layer with x values up to ≈40% over the previous pseudomorphic layer.     

Evolution of photoinduced charge in photorefractive crystal under pulsed photoinjection conditions

Phenomena that accompany pulsed data recording in a photorefractive crystal are considered. A nonlinear problem of the relaxation of a charge generated in a photoconducting material under the action of a light pulse is solved. The spatiotemporal distribution of the electric field created by the photoinduced charge at a floating potential of the illuminated crystal surface is determined. The evolution of the integral pulsed response in the case of a longitudinal electro-optical modulation is studied. The obtained results can be used for analysis of the optical data recording process and for determining the drift mobility of carriers and the parameters of traps in high-ohmic materials.