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Volumetric Ultrasound Localization Microscopy of the Whole Rat Brain Microvasculature 大鼠全脑微血管的体积超声定位显微镜
Pub Date : 2022-10-13 DOI: 10.1109/OJUFFC.2022.3214185
Baptiste Heiles;Arthur Chavignon;Antoine Bergel;Vincent Hingot;Hicham Serroune;David Maresca;Sophie Pezet;Mathieu Pernot;Mickael Tanter;Olivier Couture
Technologies to visualize whole organs across scales in vivo are essential for our understanding of biology in health and disease. To date, only post-mortem techniques achieve cellular resolution across entire organs. Here, we demonstrate in vivo volumetric ultrasound localization microscopy (ULM). We detail a universal methodological pipeline including dedicated 3D ULM, motion correction and realignment algorithms, as well as post-processing quantification of cerebral blood diameter and flow. We illustrate the power of this approach, by revealing the whole rat brain vasculature at a 14-fold improved resolution of $12 ~mu text{m}$ , and cerebral blood flows ranging from 1 to 120 mm/s. The exposed methodology and results pave the way to the investigation of in vivo vascular and hemodynamic processes across the mammalian brain in health and disease.
技术可视化整个器官在体内的尺度是必不可少的,我们的健康和疾病生物学的理解。迄今为止,只有死后技术才能实现整个器官的细胞分辨率。在这里,我们展示了体内体积超声定位显微镜(ULM)。我们详细介绍了一种通用的方法管道,包括专用的3D ULM,运动校正和调整算法,以及脑血径和血流的后处理量化。我们展示了这种方法的力量,以提高14倍的分辨率($12 ~mu text{m}$)显示了整个大鼠的脑血管系统,脑血流量范围从1到120 mm/s。暴露的方法和结果为研究哺乳动物大脑健康和疾病中的体内血管和血流动力学过程铺平了道路。
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引用次数: 15
Passive Ultrasound Localization Microscopy of Nanodroplet Vaporizations During Proton Irradiation 质子辐照下纳米液滴汽化的被动超声定位显微镜研究
Pub Date : 2022-10-10 DOI: 10.1109/OJUFFC.2022.3213534
Sophie V. Heymans;Gonzalo Collado-Lara;Marta Rovituso;Hendrik J. Vos;Jan D’hooge;Nico De Jong;Koen Van Den Abeele
Superheated nanodroplets (NDs) were recently proposed for in vivo proton range verification, owing to their ability to vaporize into echogenic microbubbles (MBs) upon exposure to ionizing radiation. In a previous publication, vaporization events were detected with 2D Ultrasound Localization Microscopy (ULM) based on a pulse-echo method. Here, we introduce P-ULM, a passive version of ULM, based on the detection of acoustic signatures emitted by vaporizing NDs, without actively transmitting ultrasound. Due to the lack of a time reference for the trigger of the ND vaporization, the time differences of arrival to each transducer element are used to retrieve the position of vaporizing NDs. P-ULM, compared to ULM, can continuously detect and super-localize sparse radiation-induced vaporization events with inherent specificity against already existing microbubbles, which otherwise would hinder range verification in the presence of vascular flow. We evaluated the localization performances of both methods theoretically and experimentally, by interleaving active and passive acquisitions on ND-phantoms irradiated with protons. P-ULM offered a higher sensitivity to vaporizations, as it detected twice as many events as ULM. Both methods retrieved, in the acoustic lateral direction, the proton range and range dispersion with sub-millimeter accuracy. In the acoustic axial direction, despite a degraded theoretical resolution limit, P-ULM retrieved the proton spot size with an accuracy similar to ULM. Importantly, P-ULM detected vaporization events with high specificity in the presence of flowing MBs, which makes the technique a candidate for in vivo proton range verification in the presence of flow.
过热纳米液滴(NDs)最近被提出用于体内质子范围验证,因为它们在暴露于电离辐射时能够汽化成回声微泡(mb)。在之前的出版物中,使用基于脉冲回波方法的二维超声定位显微镜(ULM)检测汽化事件。在这里,我们介绍了P-ULM,一种被动版本的ULM,基于检测汽化nd发出的声特征,而不主动传输超声波。由于缺乏ND汽化触发的时间参考,每个传感器元件到达的时间差用于检索汽化ND的位置。与ULM相比,P-ULM可以连续检测和超定位稀疏辐射引起的汽化事件,对已经存在的微气泡具有固有的特异性,否则在存在血管流动的情况下会阻碍范围验证。我们通过在质子辐照的nd -幻影上交替进行主动和被动获取,从理论上和实验上评估了这两种方法的定位性能。P-ULM对蒸发的灵敏度更高,因为它检测到的事件是ULM的两倍。这两种方法在声学横向上都能以亚毫米精度获取质子距离和距离色散。在声轴方向上,尽管理论分辨率限制降低,但P-ULM以与ULM相似的精度检索质子斑点大小。重要的是,P-ULM在流动的mb存在下具有高特异性地检测汽化事件,这使得该技术成为存在流动的体内质子范围验证的候选技术。
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引用次数: 1
A Hand-Held 190+190 Row–Column Addressed CMUT Probe for Volumetric Imaging 手持190+190行列寻址CMUT探针体积成像
Pub Date : 2022-10-10 DOI: 10.1109/OJUFFC.2022.3213013
Rune Sixten Grass;Mathias Engholm;Andreas Spandet Havreland;Christopher Beers;Martin Lind Ommen;Stine Løvholt Grue Pedersen;Lars Nordahl Moesner;Matthias Bo Stuart;Mudabbir Tufail Bhatti;Borislav G. Tomov;Jørgen Arendt Jensen;Erik Vilain Thomsen
This paper presents the design, fabrication, and characterization of a 190+190 row-column addressed (RCA) capacitive micromachined ultrasonic transducer (CMUT) array integrated in a custom hand-held probe handle. The array has a designed 4.5 MHz center frequency in immersion and a pitch of $95~mu $ m which corresponds to $approx ~lambda $ /4. The array has a $2.14times2.14$ cm $^{2}$ footprint including an integrated apodization scheme to reduce ghost echoes when performing ultrasound imaging. The array was fabricated using a combination of fusion and anodic bonding, and a deposit, remove, etch, multistep (DREM) etch to reduce substrate coupling and improve electrode conductivity. The transducer array was wire-bonded to a rigid-flex printed circuit board (PCB), encapsulated in room temperature vulcanizing (RTV) silicone polymer, electromagnetic interference (EMI) shielded, and mounted in a 3D-milled PPSU probe handle. The probe was characterized using the SARUS experimental scanner and 3D volumetric imaging was demonstrated on scatter and wire phantoms. The imaging depth was derived from tissue mimicking phantom measurements (0.5 dB MHz $^{-1} text{cm}^{-1}$ attenuation) by estimating the SNR at varying depths. For a synthetic aperture imaging sequence with 96+96 emissions the imaging depth was 3.6 cm. The center frequency measured from the impulse response spectra in transmit and pulse-echo was 6.0 ± 0.9 MHz and 5.3 ± 0.4 MHz, and the corresponding relative bandwidths were 62.8 ± 4.5 % and 86.2 ± 10.4 %. The fabrication process showed clear improvement in relative receive sensitivity and transmit pressure uniformity compared to earlier silicon-on-insulator (SOI) based designs. However, at the same time it presented yield problems resulting in only around 55 % elements with a good response.
本文介绍了集成在定制手持探头手柄中的190+190行列寻址(RCA)电容式微机械超声换能器(CMUT)阵列的设计、制造和表征。该阵列的设计浸入中心频率为4.5 MHz,节距为$95~mu $ m,对应于$approx ~lambda $ /4。该阵列的占地面积为$2.14times2.14$ cm $^{2}$,包括一个集成的apodization方案,以减少执行超声成像时的鬼回波。该阵列采用融合和阳极键合的组合,以及沉积、去除、蚀刻、多步骤(DREM)蚀刻来减少衬底耦合并提高电极导电性。换能器阵列通过导线连接到刚性柔性印刷电路板(PCB)上,封装在室温硫化(RTV)有机硅聚合物中,屏蔽电磁干扰(EMI),并安装在3d研磨的PPSU探头手柄中。使用SARUS实验扫描仪对探针进行了表征,并在散射和丝影上进行了三维体积成像。成像深度是通过估计不同深度下的信噪比,从组织模拟幻象测量(0.5 dB MHz $^{-1} text{cm}^{-1}$衰减)得出的。96+96次发射的合成孔径成像序列,成像深度为3.6 cm。发射脉冲响应谱和脉冲回波脉冲响应谱测得的中心频率分别为6.0±0.9 MHz和5.3±0.4 MHz,相应的相对带宽为62.8±4.5 % and 86.2 ± 10.4 %. The fabrication process showed clear improvement in relative receive sensitivity and transmit pressure uniformity compared to earlier silicon-on-insulator (SOI) based designs. However, at the same time it presented yield problems resulting in only around 55 % elements with a good response.
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引用次数: 1
Acoustic Molecular Imaging Beyond the Diffraction Limit In Vivo 在体内超越衍射极限的声分子成像
Pub Date : 2022-10-05 DOI: 10.1109/OJUFFC.2022.3212342
Thomas M. Kierski;Rachel W. Walmer;James K. Tsuruta;Jianhua Yin;Emmanuel Chérin;F. Stuart Foster;Christine E. M. Demore;Isabel G. Newsome;Gianmarco F. Pinton;Paul A. Dayton
Ultrasound molecular imaging (USMI) is a technique used to noninvasively estimate the distribution of molecular markers in vivo by imaging microbubble contrast agents (MCAs) that have been modified to target receptors of interest on the vascular endothelium. USMI is especially relevant for preclinical and clinical cancer research and has been used to predict tumor malignancy and response to treatment. In the last decade, methods that improve the resolution of contrast-enhanced ultrasound by an order of magnitude and allow researchers to noninvasively image individual capillaries have emerged. However, these approaches do not translate directly to molecular imaging. In this work, we demonstrate super-resolution visualization of biomarker expression in vivo using superharmonic ultrasound imaging (SpHI) with dual-frequency transducers, targeted contrast agents, and localization microscopy processing. We validate and optimize the proposed method in vitro using concurrent optical and ultrasound microscopy and a microvessel phantom. With the same technique, we perform a proof-of-concept experiment in vivo in a rat fibrosarcoma model and create maps of biomarker expression co-registered with images of microvasculature. From these images, we measure a resolution of $23~mathrm {mu}{text {m}}$ , a nearly fivefold improvement in resolution compared to previous diffraction-limited molecular imaging studies.
超声分子成像(USMI)是一种通过对微泡造影剂(MCAs)进行成像来无创估计体内分子标记物分布的技术,这些微泡造影剂已被修饰为靶向血管内皮上的感兴趣受体。USMI与临床前和临床癌症研究尤其相关,并已用于预测肿瘤恶性程度和对治疗的反应。在过去的十年中,已经出现了一些方法,这些方法将对比度增强超声的分辨率提高了一个数量级,并允许研究人员对单个毛细血管进行无创成像。然而,这些方法不能直接转化为分子成像。在这项工作中,我们利用双频换能器、靶向造影剂和定位显微镜处理的超谐波超声成像(SpHI)展示了生物标志物在体内表达的超分辨率可视化。我们在体外使用同步光学和超声显微镜以及微血管模型验证并优化了所提出的方法。使用相同的技术,我们在大鼠纤维肉瘤模型中进行了概念验证实验,并创建了与微血管图像共同注册的生物标志物表达图谱。从这些图像中,我们测量到的分辨率为$23~ mathm {mu}{text {m}}$,与之前衍射受限的分子成像研究相比,分辨率提高了近五倍。
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引用次数: 0
Novel Phased Array Piezoelectric Micromachined Ultrasound Transducers (pMUTs) for Medical Imaging 用于医学成像的新型相控阵压电微机械超声换能器
Pub Date : 2022-09-15 DOI: 10.1109/OJUFFC.2022.3207128
Sina Sadeghpour;Sanjog Vilas Joshi;Chen Wang;Michael Kraft
Two kinds of 128 channels pMUT-based phased array ultrasound transducers are described in this paper, one with a high frequency of around 6 MHz and another with a low frequency of around 1.5 MHz. The active area of the transducer is around 25 mm long and 10 mm wide. There are in total 6270 pMUT elements in the reported arrays. For the transducer with a center frequency of 6 MHz, each pMUT has a membrane diameter of 85 $mu text{m}$ and the pitch between every two channels is 200 $mu text{m}$ . The transducer benefits from a high transmission and receive sensitivity of 44 kPa/V/Channel @ 3 cm and 204 mV/MPa, respectively. For the transducer with a center frequency of 1.5 MHz, each pMUT has a membrane diameter of $160~mu text{m}$ and the pitch between every two elements is 214 $mu text{m}$ . The proposed transducer obtained a transmit and receive sensitivity of 430 Pa/V/Channel @ 3 cm and 190 mV/MPa, respectively. The transducer has a −3dB and −6dB bandwidth of 118% and 184%, respectively. The bandwidth is higher than any previously reported transducer in any technology, such as bulk-PZT, pMUT, or capacitive MUT (cMUT). The functionality of the transducer arrays is confirmed by obtaining B-mode images in water medium.
本文介绍了两种基于pmut的128通道相控阵超声换能器,一种高频约为6 MHz,另一种低频约为1.5 MHz。换能器的有效区域约为25毫米长,10毫米宽。在报告的数组中总共有6270个pMUT元素。对于中心频率为6 MHz的传感器,每个pMUT的膜直径为85 $mu text{m}$,每两个通道之间的基音为200 $mu text{m}$。该换能器的高传输和接收灵敏度分别为44 kPa/V/通道@ 3 cm和204 mV/MPa。对于中心频率为1.5 MHz的换能器,每个pMUT的膜直径为$160~mu text{m}$,每两个元件之间的节距为214 $mu text{m}$。该传感器的发射和接收灵敏度分别为430 Pa/V/通道@ 3 cm和190 mV/MPa。换能器的- 3dB和- 6dB带宽分别为118%和184%。带宽高于任何技术中任何先前报道的传感器,例如大块pzt, pMUT或电容MUT (cMUT)。通过在水介质中获得b模图像,验证了传感器阵列的功能。
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引用次数: 9
Thermal-Mechanical Noise Modeling and Measurements of a Row-Column Addressed CMUT Probe 行列寻址CMUT探头的热机械噪声建模与测量
Pub Date : 2022-08-16 DOI: 10.1109/OJUFFC.2022.3197104
Tony Merrien;Audren Boulmé;Dominique Certon
Thermal-Mechanical (T-M) noise is a natural phenomenon occurring in Capacitive Micromachined Ultrasonic Transducers (CMUT). T-M noise is a value of great interest because it is linked to the minimal detectable pressure of a transducer and can also serve as a convenient characterization tool. Indeed, the general behavior of a CMUT array is translated through its T-M noise which does not require any external applied source to be assessed. However, T-M noise is difficult to measure, often time requires a dedicated measurement chain and is mostly based on spectrum analyzers in a carefully controlled environment. In this paper, we present a temporal technique to characterize the T-M noise of CMUT-based arrays with a commercially available amplifier and a digital oscilloscope. The approach is applied to an air coupled Row-Column Addressed (RCA) matrix array, for which the elements cannot be measured with traditional micro-probes systems. This task is performed using a Printed Circuit Board (PCB) dedicated to the characterization of RCA arrays and designed to drive rows and columns individually. Noise Power Spectral Density (PSD) modeling of the complete measurement chain is achieved using a lumped-parameter model of the RCA array element and using the amplifier gain, electrical impedance, and noise characteristics. Measurements obtained with the signal analyzer and the temporal method are in good agreement with the model. The presented characterization technique can be extended to other micromachined ultrasonic transducer probe architectures, technologies, and amplification systems.
热-机械噪声是电容式微机械超声换能器(CMUT)的一种自然现象。T-M噪声是一个非常有趣的值,因为它与传感器的最小可检测压力有关,也可以作为方便的表征工具。事实上,CMUT阵列的一般行为是通过它的T-M噪声来转换的,它不需要任何外部应用源来评估。然而,T-M噪声很难测量,通常时间需要专用的测量链,并且主要基于在精心控制的环境中的频谱分析仪。在本文中,我们提出了一种时序技术,利用商用放大器和数字示波器来表征基于cmut的阵列的T-M噪声。该方法应用于传统微探针系统无法测量的空气耦合行列寻址(RCA)矩阵阵列。该任务使用专门用于表征RCA阵列的印刷电路板(PCB)执行,并设计为单独驱动行和列。整个测量链的噪声功率谱密度(PSD)建模是使用RCA阵列元件的集总参数模型并使用放大器增益、电阻抗和噪声特性来实现的。用信号分析仪和时间法测量的结果与模型吻合较好。所提出的表征技术可以扩展到其他微机械超声换能器探头结构、技术和放大系统。
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引用次数: 1
Assessing the Microfabrication-Related Variability of the Performance of CMUT Arrays 评估微加工相关的CMUT阵列性能变异性
Pub Date : 2022-08-11 DOI: 10.1109/OJUFFC.2022.3198390
Monica La Mura;Alvise Bagolini;Patrizia Lamberti;Alessandro Stuart Savoia
This paper addresses the assessment of the variability of CMUT arrays’ electro-mechanical and acoustic performance, as related to the tolerance of the CMUT vertical dimensions due to the microfabrication process. A 3-factors 3-levels factorial sensitivity analysis is carried out to compute the main effects and the interaction effects of the moving plate thickness, the passivation layers thickness, and the sacrificial layer thickness, on the CMUT resonance frequency, collapse voltage, and static capacitance, as well as on the transmission and reception sensitivity amplitude and bandwidth and time delay in water-coupled condition. The analysis is performed by means of FEM simulations of the CMUT static behavior and dynamic response, and the findings are compared to experimental data.
本文讨论了CMUT阵列机电和声学性能可变性的评估,这与由于微加工过程导致的CMUT垂直尺寸公差有关。通过3因素3水平的析因灵敏度分析,计算了水耦合条件下动板厚度、钝化层厚度和牺牲层厚度对CMUT谐振频率、崩溃电压、静态电容以及收发灵敏度幅值、带宽和时延的主效应和交互效应。采用有限元模拟方法对CMUT的静态性能和动态响应进行了分析,并与实验数据进行了比较。
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引用次数: 2
32 Element Piezoelectric Micromachined Ultrasound Transducer (PMUT) Phased Array for Neuromodulation 用于神经调节的32元压电微机械超声换能器相控阵
Pub Date : 2022-08-05 DOI: 10.1109/OJUFFC.2022.3196823
Pannawit Tipsawat;Sheikh Jawad Ilham;Jung In Yang;Zeinab Kashani;Mehdi Kiani;Susan Trolier-Mckinstry
Interest in utilizing ultrasound (US) transducers for non-invasive neuromodulation treatment, including for low intensity transcranial focused ultrasound stimulation (tFUS), has grown rapidly. The most widely demonstrated US transducers for tFUS are either bulk piezoelectric transducers or capacitive micromachine transducers (CMUT) which require high voltage excitation to operate. In order to advance the development of the US transducers towards small, portable devices for safe tFUS at large scale, a low voltage array of US transducers with beam focusing and steering capability is of interest. This work presents the design methodology, fabrication, and characterization of 32-element phased array piezoelectric micromachined ultrasound transducers (PMUT) using $1.5~mu text{m}$ thick Pb(Zr0.52Ti $_{{mathrm {0.48}}})text{O}_{3}$ films doped with 2 mol% Nb. The electrode/piezoelectric/electrode stack was deposited on a silicon on insulator (SOI) wafer with a $2~mu text{m}$ silicon device layer that serves as the passive elastic layer for bending-mode vibration. The fabricated 32-element PMUT has a central frequency at 1.4 MHz. Ultrasound beam focusing and steering (through beamforming) was demonstrated where the array was driven with 14.6 V square unipolar pulses. The PMUT generated a maximum peak-to-peak focused acoustic pressure output of 0.44 MPa at a focal distance of 20 mm with a 9.2 mm and 1 mm axial and lateral resolution, respectively. The maximum pressure is equivalent to a spatial-peak pulse-average intensity of 1.29 W/cm2, which is suitable for tFUS application.
利用超声(US)换能器进行非侵入性神经调节治疗,包括低强度经颅聚焦超声刺激(tFUS),已经迅速增长。用于tFUS的最广泛演示的美国换能器是体压电换能器或电容式微机械换能器(CMUT),它们需要高压激励才能工作。为了推动US换能器向小型、便携式的大规模安全tFUS设备的发展,具有波束聚焦和转向能力的低压US换能器阵列引起了人们的兴趣。本文介绍了32元相控阵压电微机械超声换能器(PMUT)的设计方法、制造和表征,该换能器使用掺杂2mol % Nb的1.5~mu text{m}$厚Pb(Zr0.52Ti $_{ mathm {0.48}}})text{O}_{3}$薄膜。电极/压电/电极堆栈沉积在绝缘体硅(SOI)晶圆上,其中$2~mu text{m}$硅器件层作为弯曲模振动的被动弹性层。制造的32元PMUT的中心频率为1.4 MHz。在14.6 V方单极脉冲驱动下,演示了超声波束聚焦和转向(通过波束形成)。在焦距为20 mm时,PMUT产生的最大峰对峰聚焦声压输出为0.44 MPa,轴向分辨率为9.2 mm,横向分辨率为1mm。最大压力相当于1.29 W/cm2的空间峰值脉冲平均强度,适合于tFUS应用。
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引用次数: 4
Data-Over-Sound With PMUTs pmut的声音数据传输
Pub Date : 2022-08-05 DOI: 10.1109/OJUFFC.2022.3197126
Harshvardhan Gupta;Bibhas Nayak;Anuj Ashok;Rudra Pratap
Data-over-sound is an emerging technology for digital communication which uses frequencies at the upper bounds of human hearing, usually between 15 kHz to 25 kHz. We report a successful development of Piezoelectric Micromachined Ultrasound Transducers (PMUTs) for low-power data-over-sound applications. Piezoelectric thin films used in PMUTs can have high residual tensile stresses ranging from 300 MPa to 1.5 GPa. These stresses have the effect of increasing the resonant frequencies of the transducers, making it a challenge to fabricate low frequency devices. Using the optimum dimensions by estimating the net residual stress in the fabricated diaphragms, transducers suitable for a frequency range of 17 kHz to 21 kHz were fabricated, capable of generating as much as 83 dB of sound pressure level at a distance of 5 cm in continuous operation.
声音数据传输是一种新兴的数字通信技术,它使用人类听觉上限的频率,通常在15khz到25khz之间。我们报告了用于低功耗数据声应用的压电微机械超声换能器(PMUTs)的成功开发。用于pmut的压电薄膜具有300 MPa至1.5 GPa的高残余拉伸应力。这些应力增加了换能器的谐振频率,使制造低频器件成为一个挑战。通过估算制造膜片的净残余应力,利用最佳尺寸,制造出适用于17 kHz至21 kHz频率范围的换能器,能够在5厘米距离上连续工作时产生高达83 dB的声压级。
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引用次数: 1
Erratum to “Characterization of Multilayer Piezoelectric Stacks Down to 100K” [2022 65-82] “多层压电堆的表征降至100K”的勘误[2022 65-82]
Pub Date : 2022-07-08 DOI: 10.1109/OJUFFC.2022.3184056
Stewart Sherrit;Mircea Badescu;John B. Steeves;William E. Krieger;Clifford A. Klein;Otto R. Polanco;Carey Louise Weisberg;David Van Buren;Joseph Sauvageau;Keith Coste
In the above article [1], on the top line in Table 3, a decimal place was dropped in the piezoelectric charge coefficient d33( $mu$ m/V) at 100 K. The data reported is 10 times larger than the measured data from the slope in Figure 6 for all three maximum voltages. Here, we provide the correct table.
在上述文章[1]中,表3的上一行,在100 K时压电电荷系数d33($mu$ m/V)减少了一个小数点。对于所有三个最大电压,报告的数据比图6中斜率的测量数据大10倍。这里,我们提供了正确的表。
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引用次数: 0
期刊
IEEE open journal of ultrasonics, ferroelectrics, and frequency control
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