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Alterations in Ultrasound Scattering Following Thermal Ablation in ex vivo Bovine Liver. 离体牛肝脏热消融后超声散射的变化。
Nicholas Rubert, Tomy Varghese

Thermal ablation is a minimally invasive cancer treatment which has been rapidly gaining clinical acceptance. It is well known that thermal ablation increases the acoustic attenuation and shear modulus of tissue. In this work, we examine changes to the spatial distribution of scatterers in liver tissue following thermal ablation. Acoustic scatterers within liver tissue have frequently been modeled as pseudo-periodic. The positions of pseudo-periodic scatterers have been Gamma distributed along the beam dimension, and these scatterers are characterized by their mean scatterer spacing (MSS). Prior work have demonstrated significant changes in MSS due to diffuse liver disease, such as steatosis progressing to cirrhosis. However, relatively few results have been reported regarding changes in MSS following thermal ablation. In this study, we estimated MSS in ex vivo bovine liver by detecting local maxima in spectral coherence functions calculated using Thomson's multi-taper method. We examined a large number of uncorrelated regions of interest recorded from five normal bovine livers (~300 images from each animal). We also examined a large number of ROI's from five bovine livers following thermal coagulation. All bovine livers were obtained from a commercial meat production facility immediately following animal sacrifice and imaged within 12 hours. Thermal coagulation was induced by heating liver in saline water baths at 80° C for 45 minutes. For normal, unheated liver an MSS of approximately 1.5 mm was estimated. Following thermal ablation, an MSS of approximately 0.5 mm in thermally coagulated tissue was obtained. Frequently, studies estimating MSS in liver tissue provide an MSS estimate regardless of the state of tissue. Authors rarely present what their MSS estimation algorithm would produce if it were applied to tissue which is better modeled as a collection of uniformly, randomly distributed scatterers lacking periodicity. In this study, we found that thermal coagulation results in a loss of periodicity. The MSS of 0.5 mm corresponds to the value that a spectral coherence-based MSS algorithm would produce if presented with a signal that was generated from uniform, randomly distributed scatterers.

热消融是一种微创肿瘤治疗方法,已迅速获得临床认可。众所周知,热消融增加了组织的声衰减和剪切模量。在这项工作中,我们研究了热消融后肝组织中散射体空间分布的变化。肝组织内的声散射体经常被建模为伪周期。伪周期散射体的位置沿波束尺寸呈伽玛分布,用平均散射体间距(MSS)表征。先前的研究表明,弥漫性肝病(如脂肪变性进展为肝硬化)会导致MSS发生显著变化。然而,关于热消融后MSS变化的报道相对较少。在这项研究中,我们通过检测使用汤姆逊的多锥度方法计算的光谱相干函数的局部最大值来估计离体牛肝脏的MSS。我们检查了从5只正常牛肝脏中记录的大量不相关的感兴趣区域(每只动物约300张图像)。我们还检查了热凝后5只牛肝脏的大量ROI。所有牛肝脏均在动物献祭后立即从商业肉类生产设施获得,并在12小时内成像。在80°C盐水浴中加热肝脏45分钟,诱导热凝。对于正常的未加热肝脏,估计MSS约为1.5 mm。热消融后,在热凝固组织中获得约0.5 mm的MSS。通常,估计肝组织中MSS的研究提供了一个不考虑组织状态的MSS估计。作者很少提出他们的MSS估计算法将产生什么,如果它被应用于组织更好地建模为一个集合均匀,随机分布的散射体缺乏周期性。在这项研究中,我们发现热凝聚导致周期性的丧失。0.5 mm的MSS对应于基于谱相干的MSS算法在面对均匀随机分布的散射体产生的信号时所产生的值。
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引用次数: 0
Improved Detection of Kidney Stones Using an Optimized Doppler Imaging Sequence. 利用优化多普勒成像序列改进肾结石的检测。
Bryan Cunitz, Barbrina Dunmire, Marla Paun, Oleg Sapozhnikov, John Kucewicz, Ryan Hsi, Franklin Lee, Matthew Sorensen, Jonathan Harper, Michael Bailey

Kidney stones have been shown to exhibit a "twinkling artifact" (TA) under Color-Doppler ultrasound. Although this technique has better specificity than conventional Bmode imaging, it has lower sensitivity. To improve the overall performance of using TA as a diagnostic tool, Doppler output parameters were optimized in-vitro. The collected data supports a previous hypothesis that TA is caused by random oscillations of micron sized bubbles trapped in the cracks and crevices of kidney stones. A set of optimized parameters were implemented such that that the MI & TI remained within the FDA approved limits. Several clinical kidney scans were performed with the optimized settings and were able to detect stones with improved SNR relative to the default settings.

肾结石在彩色多普勒超声下显示出“闪烁伪影”(TA)。虽然该技术比传统的b模成像具有更好的特异性,但其灵敏度较低。为了提高TA作为诊断工具的整体性能,体外优化了多普勒输出参数。收集到的数据支持了先前的假设,即TA是由被困在肾结石裂缝和裂隙中的微米级气泡的随机振荡引起的。实施了一组优化参数,使MI和TI保持在FDA批准的范围内。在优化的设置下进行了几次临床肾脏扫描,并且能够以相对于默认设置的改进的信噪比检测结石。
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引用次数: 19
Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study. 超声推进肾结石:人体可行性研究的初步结果。
Michael Bailey, Bryan Cunitz, Barbrina Dunmire, Marla Paun, Franklin Lee, Susan Ross, James Lingeman, Michael Coburn, Hunter Wessells, Mathew Sorensen, Jonathan Harper

One in 11 Americans has experienced kidney stones, with a 50% average recurrence rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to expel small stones or residual fragments before they become a recurrent problem. Reported here are preliminary findings from the first investigational use of UP in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2 probe to generate real-time B-mode imaging and targeted "push" pulses on demand. There are three arms of the study: de novo stones, post-lithotripsy fragments, and the preoperative setting. A pain questionnaire is completed prior to and following the study. Movement is classified based on extent. Patients are followed for 90 days. Ten subjects have been treated to date: three de novo, five post-lithotripsy, and two preoperative. None of the subjects reported pain associated with the treatment or a treatment related adverse event, beyond the normal discomfort of passing a stone. At least one stone was moved in all subjects. Three of five post-lithotripsy subjects passed a single or multiple stones within 1-2 weeks following treatment; one subject passed two (1-2 mm) fragments before leaving clinic. In the pre-operative studies we successfully moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments where the clinical image and initial ultrasound examination indicated a single large stone.

每11个美国人中就有一个患有肾结石,在5-10年内平均复发率为50%。超声波推进(UP)提供了一种潜在的方法,在小结石或残余碎片成为复发性问题之前将其排出体外。这里报告的是首次在人类中使用UP的初步调查结果。该设备使用Verasonics超声引擎和飞利浦HDI C5-2探头,根据需要产生实时b模式成像和有针对性的“推送”脉冲。该研究分为三组:新生结石、碎石后碎片和术前设置。在研究之前和之后完成疼痛问卷。运动是根据程度来分类的。患者随访90天。到目前为止,已有10名患者接受了治疗:3名新生患者,5名碎石术后患者,2名术前患者。除了正常的排结石不适外,没有受试者报告与治疗相关的疼痛或治疗相关的不良事件。所有科目中至少有一块石头被移动。碎石后5名受试者中有3名在治疗后1-2周内排出了单个或多个结石;一名受试者在离开诊所前通过了两个(1-2毫米)碎片。在术前研究中,我们成功地移动了7 - 8毫米的结石。在四名受试者中,UP显示多个结石碎片,而临床图像和初始超声检查显示单个大结石。
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引用次数: 3
Shockwave lithotripsy with renoprotective pause is associated with renovascular vasoconstriction in humans. 伴有肾保护暂停的冲击波碎石术与人类肾血管收缩有关。
Michael Bailey, Franklin Lee, Ryan Hsi, Marla Paun, Barbrina Dunmire, Ziyue Liu, Mathew Sorensen, Jonathan Harper

Animal studies have shown that shock wave lithotripsy (SWL) delivered with an initial course of low-energy shocks followed by a pause reduces renal injury. The pause correlates with increased arterial resistive index (RI) during SWL as measured by ultrasound. This suggests that renal vasoconstriction is associated with protecting the kidney from injury. This study explored whether a similar increase in RI is observed in humans. Patients were prospectively recruited from two hospitals. All received an initial dose of 250 lowest energy shocks followed by a two-minute pause. Shock power was then ramped up at the discretion of the physician; shock rate was maintained at 1 Hz. Spectral Doppler velocity measurements were taken from an interlobar artery at baseline after induction, during the pause at 250 shocks, after 750 shocks, after 1500 shocks, and at the end of the procedure. RI was calculated from the peak systolic and end diastolic velocities and a linear mixed-effects model was used to compare RIs. The statistical model accounted for age, gender, laterality, and body mass index (BMI). Measurements were taken from 15 patients. Average RI ± standard deviation pretreatment, after 250 shocks, after 750 shocks, after 1500 shocks, and post treatment was 0.68 ± 0.06, 0.71 ± 0.07, 0.73 ± 0.06, 0.75 ± 0.07 and 0.75 ± 0.06, respectively. RI was found to be significantly higher after 250 shocks compared to pretreatment (p = 0.04). RI did not correlate with age, gender, BMI, or treatment side. This is suggestive that allowing a pause for renal vascular vasoconstriction to develop may be beneficial, and can be monitored for during SWL, providing real-time feedback as to when the kidney is protected.

动物研究表明,冲击波碎石术(SWL)以低能量休克为初始过程,然后暂停,可减少肾脏损伤。超声测量SWL期间,暂停与动脉阻力指数(RI)增加相关。这表明肾脏血管收缩与保护肾脏免受损伤有关。这项研究探讨了是否在人类中观察到类似的RI增加。前瞻性地从两家医院招募患者。所有人都接受了250次最低能量冲击的初始剂量,然后暂停两分钟。然后根据医生的判断加大电击力度;电击频率维持在1hz。在诱导后的基线、250次冲击后的暂停、750次冲击后、1500次冲击后和手术结束时,从叶间动脉处测量频谱多普勒速度。从收缩峰值和舒张末期速度计算RI,并使用线性混合效应模型来比较RI。统计模型考虑了年龄、性别、侧卧和身体质量指数(BMI)。对15名患者进行了测量。预处理、250次、750次、1500次和处理后的平均RI±标准差分别为0.68±0.06、0.71±0.07、0.73±0.06、0.75±0.07和0.75±0.06。与预处理相比,250次冲击后的RI显著升高(p = 0.04)。RI与年龄、性别、BMI或治疗方无关。这提示允许肾脏血管收缩的暂停发展可能是有益的,并且可以在SWL期间进行监测,提供肾脏何时受到保护的实时反馈。
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引用次数: 0
Label-free Detection of Protein Released during Platelet Activation by CNT-Enhanced Love Mode SAW Sensors. 利用 CNT 增强型爱模式声表面波传感器对血小板活化过程中释放的蛋白质进行无标记检测。
Huiyan Wu, Hongfei Zu, Qing-Ming Wang, Gangyi Zhao, Jamesu H-C Wang

Platelet-rich plasma (PRP) has been applied in a series of clinical treatments. PRP contains high-concentrated platelets, which, when activated, could secret a variety of growth factors and cytokines, to promote and/or enhance healing of injured tissues. Non-activated platelets suspension could be prepared by an isolation method of centrifugation and washing currently. However, it is not clear whether platelets, if any, are already activated during this process and there is no simple method to monitor their activation accordingly. Shear-Horizontal Surface Acoustic Wave sensors (SH-SAW, Love Mode) are promising in fundamental biology as well as biomedical engineering, detecting cell behaviors in liquid in a non-invasive, simple and quantitative manner. In this study, Love mode sensors are adopted for the label-free detection of protein secreted by platelets. Carbon nanotube (CNT) is reported as an advisable platform of both non-specific protein adsorption and specific protein binding. For further improvement of Love mode sensor performance, novel CNT -coated parylene-C film is prepared on its surface as both the acoustic-wave-guiding layer and bio-interface layer. The S21 loss curves of Love mode sensors were recorded and the corresponding resonance frequencies were extracted. The results showed that the CNT-enhanced sensor possessed an increased resonance frequency shift when compared to normal sensor with single parylene-C film under identical collagen concentrations. Then, the modified sensor is used for label-free detection of protein released by various concentrations of platelets. The results revealed high sensitivity and consistency, indicating the potential of CNT-enhanced Love mode sensors in cell-based applications.

富血小板血浆(PRP)已被应用于一系列临床治疗中。血小板富集血浆含有高浓度血小板,激活后可分泌多种生长因子和细胞因子,促进和/或增强损伤组织的愈合。非活化血小板悬浮液目前可通过离心和洗涤的分离方法制备。不过,目前还不清楚在此过程中是否有血小板被激活,也没有简单的方法来监测其激活情况。剪切-水平表面声波传感器(SH-SAW,Love 模式)在基础生物学和生物医学工程中大有可为,它能以非侵入性、简单和定量的方式检测液体中的细胞行为。本研究采用爱模式传感器对血小板分泌的蛋白质进行无标记检测。据报道,碳纳米管(CNT)是非特异性蛋白质吸附和特异性蛋白质结合的理想平台。为了进一步提高爱模式传感器的性能,在其表面制备了新型 CNT 涂层对二甲苯-C 薄膜,作为声波导向层和生物界面层。记录了爱模式传感器的 S21 损耗曲线,并提取了相应的共振频率。结果表明,在胶原蛋白浓度相同的情况下,CNT 增强型传感器的共振频率偏移与单层对二甲苯-C 薄膜的普通传感器相比有所增加。然后,将改进后的传感器用于无标记检测不同浓度血小板释放的蛋白质。结果表明,这种传感器具有高灵敏度和高一致性,表明 CNT 增强爱模式传感器在基于细胞的应用中具有巨大潜力。
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引用次数: 0
Characterization of nonlinear ultrasound fields of 2D therapeutic arrays. 二维治疗阵列非线性超声场的特征。
Petr V Yuldashev, Wayne Kreider, Oleg A Sapozhnikov, Navid Farr, Ari Partanen, Michael R Bailey, Vera Khokhlova

A current trend in high intensity focused ultrasound (HIFU) technologies is to use 2D focused phased arrays that enable electronic steering of the focus, beamforming to avoid overheating of obstacles (such as ribs), and better focusing through inhomogeneities of soft tissue using time reversal methods. In many HIFU applications, the acoustic intensity in situ can reach thousands of W/cm2 leading to nonlinear propagation effects. At high power outputs, shock fronts develop in the focal region and significantly alter the bioeffects induced. Clinical applications of HIFU are relatively new and challenges remain for ensuring their safety and efficacy. A key component of these challenges is the lack of standard procedures for characterizing nonlinear HIFU fields under operating conditions. Methods that combine low-amplitude pressure measurements and nonlinear modeling of the pressure field have been proposed for axially symmetric single element transducers but have not yet been validated for the much more complex 3D fields generated by therapeutic arrays. Here, the method was tested for a clinical HIFU source comprising a 256-element transducer array. A numerical algorithm based on the Westervelt equation was used to enable 3D full-diffraction nonlinear modeling. With the acoustic holography method, the magnitude and phase of the acoustic field were measured at a low power output and used to determine the pattern of vibrations at the surface of the array. This pattern was then scaled to simulate a range of intensity levels near the elements up to 10 W/cm2. The accuracy of modeling was validated by comparison with direct measurements of the focal waveforms using a fiber-optic hydrophone. Simulation results and measurements show that shock fronts with amplitudes up to 100 MPa were present in focal waveforms at clinically relevant outputs, indicating the importance of strong nonlinear effects in ultrasound fields generated by HIFU arrays.

目前,高强度聚焦超声(HIFU)技术的发展趋势是使用二维聚焦相控阵,以实现聚焦的电子转向、避免障碍物(如肋骨)过热的波束成形,以及使用时间反转方法更好地聚焦软组织的不均匀性。在许多 HIFU 应用中,原位声强可达数千瓦/平方厘米,从而导致非线性传播效应。在高功率输出时,病灶区域会出现冲击前沿,从而显著改变所诱导的生物效应。HIFU 的临床应用相对较新,在确保其安全性和有效性方面仍面临挑战。这些挑战的一个关键因素是缺乏在工作条件下表征非线性 HIFU 场的标准程序。针对轴对称单元件传感器提出了结合低振幅压力测量和压力场非线性建模的方法,但尚未对治疗阵列产生的复杂得多的三维场进行验证。在此,该方法针对由 256 个元素换能器阵列组成的临床 HIFU 源进行了测试。使用基于 Westervelt 方程的数值算法实现了三维全衍射非线性建模。利用声全息法,可以在低功率输出时测量声场的幅度和相位,并确定阵列表面的振动模式。然后对该模式进行缩放,以模拟元件附近高达 10 W/cm2 的一系列强度水平。通过与使用光纤水听器直接测量的焦点波形进行比较,验证了建模的准确性。模拟结果和测量结果表明,在临床相关输出的焦点波形中存在振幅高达 100 兆帕的冲击前沿,这表明了 HIFU 阵列产生的超声场中强非线性效应的重要性。
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引用次数: 0
Should the mechanical index be revised for ARFI imaging? 是否应该修改ARFI成像的机械指标?
Charles C Church, Cecille Labuda, Kathryn Nightingale

The mechanical index (MI) quantifies the likelihood that exposure to diagnostic ultrasound will produce an adverse biological effect by a nonthermal mechanism. The current formulation of the MI is based on inertial cavitation thresholds in two liquids, water and blood, as calculated by a formalism assuming very short pulse durations. Although tissue contains a high proportion of water, it is not a liquid but a viscoelastic solid. Further, acoustic radiation force impulse imaging employs high-intensity pulses up to several hundred acoustic periods long. The effect of these differences was studied in water, blood and five representative tissues.

机械指数(MI)量化的可能性,暴露于诊断超声将产生不利的生物效应的非热机制。目前的惯性空化阈值公式是基于水和血液这两种液体的惯性空化阈值,通过假设脉冲持续时间很短的一种形式来计算。虽然组织含有很高比例的水,但它不是液体,而是粘弹性固体。此外,声辐射力脉冲成像采用长达几百个声周期的高强度脉冲。在水、血液和五种代表性组织中研究了这些差异的影响。
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引用次数: 14
Tissue Atomization by High Intensity Focused Ultrasound. 高强度聚焦超声组织雾化。
Pub Date : 2012-10-01 Epub Date: 2013-07-18 DOI: 10.1109/ultsym.2012.0251
Julianna Simon, Oleg Sapozhnikov, Vera Khokhlova, Yak-Nam Wang, Lawrence Crum, Michael Bailey

Liquid atomization and fountain formation by focused ultrasound was first published by Wood and Loomis [1]. Since then, the cavitation-wave hypothesis emerged to explain atomization in a fountain, which states atomization arises from a combination of surface capillary waves and the collapse of cavitation bubbles. More recently, high intensity focused ultrasound (HIFU) has been shown to fractionate tissue through either pulsed-cavitation or millisecond boiling histotripsy therapies; however it is unclear how millimeter-size boiling bubbles or cavitation bubble clouds fractionate tissue into submicron-size fragments. The objective of this work is to test the hypothesis experimentally that atomization and fountain formation occurs similarly in liquids and tissues and results in tissue erosion. A 2-MHz HIFU transducer operating at peak in situ pressures of 50 MPa and -11 MPa (linear intensity = 14,000 W/cm2) was focused at the interface between a liquid or tissue and air. A high-speed camera was used to monitor atomization and fountain formation in water, ethanol, glycerol, bovine liver, and porcine blood clots. The in situ linear intensity threshold for consistent atomization in one 10-ms pulse increased in the order: ethanol (180 W/cm2) < blood clot (250 W/cm2) < water (350 W/cm2) < liver (6200 W/cm2); glycerol did not atomize. Average jet velocities for the initial spray at the maximum acoustic intensity were similar for all materials and on the order of 20 m/s. The tissue erosion rate of liver approached saturation at around 300 10-ms pulses repeated at 1 Hz, which had an average erosion volume of 25.7±10.9 mm3. While tissue atomization and fountain formation does not completely mimic what is observed in liquids, atomization provides a plausible explanation of how tissue is fractionated in millisecond boiling and possibly even cavitation cloud histotrispy therapies.

聚焦超声的液体雾化和喷泉形成最早由Wood和Loomis发表[1]。从那时起,出现了空化波假说来解释喷泉中的原子化,该假说认为,原子化是由表面毛细波和空化泡的崩溃结合而产生的。最近,高强度聚焦超声(HIFU)已被证明可以通过脉冲空化或毫秒沸腾组织切片治疗来分离组织;然而,目前尚不清楚毫米大小的沸腾气泡或空化气泡云是如何将组织分解成亚微米大小的碎片的。这项工作的目的是通过实验来验证这样一个假设,即雾化和喷泉形成在液体和组织中发生相似,并导致组织侵蚀。在50 MPa和-11 MPa(线性强度= 14000 W/cm2)的峰值原位压力下工作的2 mhz HIFU传感器聚焦在液体或组织与空气之间的界面上。高速摄像机用于监测水、乙醇、甘油、牛肝和猪血块中的雾化和喷泉形成。在一个10-ms脉冲中,一致雾化的原位线性强度阈值依次增大:乙醇(180 W/cm2) <血凝块(250 W/cm2) <水(350 W/cm2) <肝脏(6200 W/cm2);甘油不雾化。在最大声强下,所有材料初始喷雾的平均喷射速度相似,约为20 m/s。以1 Hz频率重复300次10-ms脉冲时,肝脏组织侵蚀率接近饱和,平均侵蚀体积为25.7±10.9 mm3。虽然组织雾化和喷泉形成并不能完全模拟在液体中观察到的情况,但雾化为组织在毫秒沸腾甚至可能是空化云历史疗法中如何分离提供了合理的解释。
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引用次数: 2
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IEEE International Ultrasonics Symposium : [proceedings]. IEEE International Ultrasonics Symposium
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