Shear-wave generation using acoustic radiation force: in vivo and ex vivo results

Acoustic radiation force impulse (ARFI) imaging involves the mechanical excitation of tissue using localized, impulsive radiation force. This results in shear-wave propagation away from the region of excitation. Using a single diagnostic transducer on a modified commercial ultrasound (US) scanner with conventional beam-forming architecture, repeated excitations with multiple look directions facilitate imaging shear-wave propagation. Direct inversion methods are then applied to estimate the associated Young's modulus. Shear-wave images are generated in tissue-mimicking phantoms, ex vivo human breast tissue and in vivo in the human abdomen. Mean Young's modulus values of between 3.8 and 5.6 kPa, 11.7 kPa and 14.0 kPa were estimated for fat, fibroadenoma and skin, respectively. Reasonable agreement is demonstrated between structures in matched B-mode and reconstructed modulus images. Although the relatively small magnitude of the displacement data presents some challenges, the reconstructions suggest the clinical feasibility of radiation force induced shear-wave imaging. (E-mail: kathy.nightingale@duke.edu)     

Prospective evaluation of acoustic radiation force impulse technology in the differentiation of thyroid nodules: accuracy and interobserver variability assessment

Purpose

The aim of this study is to assess the diagnostic efficacy and interobserver agreement of acoustic radiation force impulse (ARFI) elasticity imaging in differentiating thyroid nodules.

Methods

In our study, 74 consecutive patients (52 females, 22 males; age range 27–77 years, mean: 41 years) with 82 thyroid nodules (60 benign nodules, and 22 malignant) were examined by two radiologists with different experience. Patients underwent either cytology using fine needle aspiration cytology or thyroid surgery. The diagnostic performance of the two operators at ARFI with sensitivity, specificity, positive predictive and negative predictive value, and ROC curves was estimated. Inter-reader variability between the two operators was defined using Cohen’s k.

Results

According to receiver operating characteristics ROC curves (AUROC = 0.86 for observer 1; 0.81 for observer 2) sensitivity, specificity, PPV and NPV of reader 1 and 2 were respectively: 90, 75, 90.91 and 96.55 %; (cut-off value of shear wave: 2.455 m/s); 90, 72, 90 and 96.90 % (cut-off value shear wave: 2.365 m/s). Concordance between the two operators was good (k = 0.755).

Conclusions

This work is a feasibility study evaluating ARFI imaging. Its results suggest that ARFI imaging is a reproducible method which can be utilized with good diagnostic performance in the thyroid for discriminating benign and malignant nodules using the cut-off value of 2.455 m/s. However, larger studies are needed to validate this method.     

Enhanced targeting of ultrasound contrast agents using acoustic radiation force

Contrast-enhanced ultrasound has shown significant promise as a molecular imaging modality. However, one potential drawback is the difficulty that ultrasound contrast agents (UCA) may have in achieving adhesion to target molecules on the vascular endothelium. Microbubble UCA exhibit a lateral migration toward the vessel axis in laminar flow, preventing UCA contact with the endothelium. In the current study, we have investigated low-amplitude acoustic radiation as a mechanism to move circulating UCA toward targeted endothelium. Intravital microscopy was used to assess the retention of microbubble UCA targeted to P-selectin in the mouse cremaster microcirculation and femoral vessels. Acoustic treatment enhanced UCA retention to P-selectin four-fold in cremaster venules and in the femoral vein and 20-fold in the femoral artery. These results suggest acoustic treatment as a mechanism for enabling ultrasound-based molecular imaging in blood vessels with hemodynamic and anatomical conditions otherwise adversarial for UCA retention.     

Acoustic radiation contrast in MR images for breast cancer diagnostics--initial phantom study

Acoustic radiation contrast in magnetic resonance images is an approach to visualize the changes in ultrasonic loss and viscoelastic changes of the sample with the resolution of a magnetic resonance imaging (MRI) system. By irradiating ultrasound (US) into a tissue-mimicking sample, a displacement along the US beam path caused by the acoustic radiation force is obtained. This displacement varies with the US intensity, the duration of irradiation, the US attenuation and the viscoelastic properties of the sample. US pulses of 2.5 MHz with a duration of 20 ms and an intensity of <17 W/cm² are used. An MRI sequence was programmed to produce images in which the magnitude of the displacement is visualized by gray value changes. In addition, a finite element simulation of the measurements was performed to demonstrate the feasibility of the method. Through examination of the measurements and the simulations, information about viscoelastic changes was achieved. In this work, measurements on different breast phantoms are presented. (E-mail: marcus.radicke@gmx.de)     

声脉冲辐射力成像技术在肝脏疾病中的应用

声脉冲辐射力成像(ARFI)技术是近年来新兴的超声弹性成像技术,具备定性和定量分析组织弹性的能力。本文就ARFI技术在肝脏疾病的应用现状及进展进行综述。     

Preliminary Results of Acoustic Radiation Force Impulse (ARFI) Ultrasound Imaging of Breast Lesions

The aim of this study was to determine the appearance of breast lesions using acoustic radiation force impulse imaging (ARFI) and to correlate the ARFI values with the pathologic results. The area ratio (AR) and virtual touch tissue quantification (VTQ) values were analyzed in 86 patients (mean age 45.6 years, range 17-78 years) with 92 breast lesions (65 benign, 27 malignant; mean size 25.7 mm). The diagnostic performance of ultrasound (US) alone and US plus ARFI values were compared with respect to sensitivity, specificity and area under the curve (AUC) using a receiver operating characteristic curve analysis. The mean AR of the benign lesions (1.08 ± 0.21) differed from that of the malignant lesions (1.99 ± 0.63; p < 0.0001), as did the mean VTQ values (3.25 ± 2.03 m/s vs. 8.22 ± 1.27 m/s; p < 0.0001). In conclusion, ARFI provides quantitative elasticity measurements, which may complement B-mode US and potentially improve the characterization of breast lesions.     

Quantifying hepatic shear modulus in vivo using acoustic radiation force

The speed at which shear waves propagate in tissue can be used to quantify the shear modulus of the tissue. As many groups have shown, shear waves can be generated within tissues using focused, impulsive, acoustic radiation force excitations, and the resulting displacement response can be ultrasonically tracked through time. The goals of the work herein are twofold: (i) to develop and validate an algorithm to quantify shear wave speed from radiation force-induced, ultrasonically-detected displacement data that is robust in the presence of poor displacement signal-to-noise ratio and (ii) to apply this algorithm to in vivo datasets acquired in human volunteers to demonstrate the clinical feasibility of using this method to quantify the shear modulus of liver tissue in longitudinal studies. The ultimate clinical application of this work is noninvasive quantification of liver stiffness in the setting of fibrosis and steatosis. In the proposed algorithm, time-to-peak displacement data in response to impulsive acoustic radiation force outside the region of excitation are used to characterize the shear wave speed of a material, which is used to reconstruct the material's shear modulus. The algorithm is developed and validated using finite element method simulations. By using this algorithm on simulated displacement fields, reconstructions for materials with shear moduli (mu) ranging from 1.3-5 kPa are accurate to within 0.3 kPa, whereas stiffer shear moduli ranging from 10-16 kPa are accurate to within 1.0 kPa. Ultrasonically tracking the displacement data, which introduces jitter in the displacement estimates, does not impede the use of this algorithm to reconstruct accurate shear moduli. By using in vivo data acquired intercostally in 20 volunteers with body mass indices ranging from normal to obese, liver shear moduli have been reconstructed between 0.9 and 3.0 kPa, with an average precision of +/-0.4 kPa. These reconstructed liver moduli are consistent with those reported in the literature (mu = 0.75-2.5 kPa) with a similar precision (+/-0.3 kPa). Repeated intercostal liver shear modulus reconstructions were performed on nine different days in two volunteers over a 105-day period, yielding an average shear modulus of 1.9 +/- 0.50 kPa (1.3-2.5 kPa) in the first volunteer and 1.8 +/- 0.4 kPa (1.1-3.0 kPa) in the second volunteer. The simulation and in vivo data to date demonstrate that this method is capable of generating accurate and repeatable liver stiffness measurements and appears promising as a clinical tool for quantifying liver stiffness.     

Acoustic Radiation Force Impulse Elastography for the Evaluation of Focal Solid Hepatic Lesions: Preliminary Findings

This study was designed to investigate the potential usefulness of acoustic radiation force impulse (ARFI) elastography to evaluate focal solid hepatic lesions. In total, 51 patients with 60 focal hepatic lesions, which included 17 hemangiomas, 25 hepatocellular carcinomas (HCCs), 15 metastases and three cholangiocarcinomas, underwent ARFI elastography. The lesions were classified into three groups: Group I consisted of metastatic liver tumors and cholangiocarcinomas, group II consisted of HCCs and group III consisted of hemangiomas. The stiffness and conspicuity of the tumors as depicted on ARFI elastography and the echogenicity and conspicuity of the tumors on corresponding B-mode images were analyzed. Shear wave velocity was obtained to quantify stiffness for 36 focal hepatic lesions: 11 hemangiomas, 17 HCCs and eight other malignant lesions.     

声脉冲辐射力成像在糖尿病患者肾脏检查中的应用

目的初步探讨声脉冲辐射力成像(ARFI)在评估糖尿病患者肾脏弹性硬度中的价值。方法选取单纯糖尿病组19例,糖尿病肾病组18例,体检健康者38例为对照组,ARFI检测其肾皮质、肾髓质及肾窦部的弹性指数(EI)。结果对照组、单纯糖尿病组及糖尿病肾病组的EI均在肾皮质、肾髓质、肾窦依次减小(P0.01)。肾皮质、肾髓质和肾窦部EI在对照组、单纯糖尿病组及糖尿病肾病组间依次减小(P0.05)。结论 ARFI能无创地反映肾脏组织不同部位的弹性程度,早期发现糖尿病肾脏组织的弹性异常,对临床评估糖尿病肾脏损害具有一定的价值。     

Shear wave elasticity imaging based on acoustic radiation force and optical detection

Tissue elasticity is closely related to the velocity of shear waves within biologic tissue. Shear waves can be generated by an acoustic radiation force and tracked by, e.g., ultrasound or magnetic resonance imaging (MRI) measurements. This has been shown to be able to noninvasively map tissue elasticity in depth and has great potential in a wide range of clinical applications including cancer and cardiovascular diseases. In this study, a highly sensitive optical measurement technique is proposed as an alternative way to track shear waves generated by the acoustic radiation force. A charge coupled device (CCD) camera was used to capture diffuse photons from tissue mimicking phantoms illuminated by a laser source at 532 nm. CCD images were recorded at different delays after the transmission of an ultrasound burst and were processed to obtain the time of flight for the shear wave. A differential measurement scheme involving generation of shear waves at two different positions was used to improve the accuracy and spatial resolution of the system. The results from measurements on both homogeneous and heterogeneous phantoms were compared with measurements from other instruments and demonstrate the feasibility and accuracy of the technique for imaging and quantifying elasticity. The relative error in estimation of shear wave velocity can be as low as 3.3% with a spatial resolution of 2 mm, and increases to 8.8% with a spatial resolution of 1 mm for the medium stiffness phantom. The system is shown to be highly sensitive and is able to track shear waves propagating over several centimetres given the ultrasound excitation amplitude and the phantom material used in this study. It was also found that the reflection of shear waves from boundaries between regions with different elastic properties can cause significant bias in the estimation of elasticity, which also applies to other shear wave tracking techniques. This bias can be reduced at the expense of reduced spatial resolution.     

超声造影联合声脉冲辐射力成像诊断常规超声难以定性的肝脏局灶性病变的价值

目的探讨超声造影与联合声脉冲辐射力成像(ARFI)对常规超声难以定性的肝脏局灶性病变的诊断价值。方法 115例常规超声难以定性的肝脏局灶性病变患者,共137个病灶,ARFI获取声触诊组织定量(VTQ),随后对病灶行超声造影检查,病灶均经病理或增强CT、MRI证实。构建ROC曲线比较超声造影及超声造影联合ARFI的诊断价值。结果超声造影联合ARFI对肝脏局灶性病变诊断敏感性、特异性及准确性均高于超声造影(P0.05)。对于超声造影表现不典型15个病灶联合ARFI诊断准确率为93.3%(14/15)。结论 ARFI能够提高超声造影诊断的准确性,有助于诊断超声造影表现不典型病灶。     

甲状腺癌声脉冲辐射力弹性成像特征分析

目的 探讨甲状腺癌在声脉冲辐射力(ARFI)弹性成像声触诊组织定性成像(VTI)和声触诊组织定量(VTQ)成像上的特征.方法 分析20例甲状腺癌患者21个癌灶的ARFI成像特征.将甲状腺结节的VTI图像分为6级,评估甲状腺癌VTI图像分布特征.应用VTQ技术检测甲状腺癌及相同深度处周围甲状腺组织的横向剪切波速度(SWV)并进行比较分析.结果 21个甲状腺癌病灶VTI图像分析:1级0个;2级1个;3级2个;4级8个;5级7个;6级3个;VTI图像4级及以上占85.7%(18/21).甲状腺癌病灶VTQ检测SWV平均值为(4.70±2.79)m/s(范围:2.14～9.00 m/s);与其相同深度处周邻甲状腺组织的SWV平均值为(2.16±0.46)m/s(范围:1.37～3.33 m/s),两者比较差异有统计学意义(t=4.109,P＜0.01);21个甲状腺癌病灶与相同深度处周邻甲状腺组织的SWV比值的平均值为2.23±1.43(范围:0.97～6.16).结论 AFRI技术、VTI和VTQ能定性及定量反映甲状腺癌病灶的硬度,可能对判断甲状腺癌性质提供诊断依据.     

In vivo guidance and assessment of liver radio-frequency ablation with acoustic radiation force elastography

The initial results from clinical trials investigating the utility of acoustic radiation force impulse (ARFI) imaging for use with radio-frequency ablation (RFA) procedures in the liver are presented. To date, data have been collected from 6 RFA procedures in 5 unique patients. Large displacement contrast was observed in ARFI images of both pre-ablation malignancies (mean 7.5 dB, range 5.7-11.9 dB) and post-ablation thermal lesions (mean 6.2 dB, range 5.1-7.5 dB). In general, ARFI images provided superior boundary definition of structures relative to the use of conventional sonography alone. Although further investigations are required, initial results are encouraging and demonstrate the clinical promise of the ARFI method for use in many stages of RFA procedures.     

声触诊组织量化技术在早期糖尿病肾病诊断中的应用价值

目的 探讨声触诊组织量化技术在糖尿病肾病早期诊断中的价值.方法 选取63例确诊为2型糖尿病的患者,在血糖控制理想、肌酐正常的前提下根据24 h尿微量白蛋白排出量（UA）将患者分为3组,Ⅰ组（UA＜ 30 mg）、Ⅱ组（30 mg≤UA ＜300 mg）、Ⅲ组（UA≥300 mg）,同时选取25例健康者为正常对照组（Ⅳ组）.采用声触诊组织量化技术分别测量各分组肾中部实质的剪切波速度（SWV）,进行统计学分析.结果 各组肾实质SWV值与UA值呈正相关.Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组的SWV平均值分别为（2.04±0.10）m/s、（2.34±0.16）m/s、（2.76±0.32） m/s、（1.96±0.21） m/s,Ⅰ组与对照组SWV值比较无统计学差异（P＞0.05）,Ⅱ组、Ⅲ组与对照组SWV值比较均有统计学差异（P＜0.05）.Ⅰ组与Ⅱ组、Ⅰ组与Ⅲ组、Ⅱ组与Ⅲ组SWV值比较均有统计学差异（P＜0.05）.结论 肾实质SWV随肾脏损害的加重而加快,声触诊组织量化技术可以无创地量化反映早期糖尿病肾病患者肾脏损害的程度,辅助诊断.     

Impact of nonlinear distortion on acoustic radiation force elastography

High-intensity focused ultrasound (HIFU) produces an acoustic radiation force that induces tissue displacement, which can be measured by monitoring time shifts in the backscattered signals from interrogation pulses. If the pulse occurs simultaneously with the HIFU, the arrival time of the backscatter will be biased because nonlinearity associated with the HIFU changes the local sound speed. Measurements of the pressure field using 1.1 MHz HIFU and a 7.5 MHz pulse in water exhibited a nonlinearly induced apparent displacement (NIAD) that varied with the HIFU pressure, propagation distance and the timing of the pulse relative to the HIFU. Nonlinear simulations employing the KZK equation predicted NIADs that agreed with measurements. Experiments with chicken breast demonstrated a NIAD with magnitude similar to that expected from the radiation force. Finally it was shown that if two pulses were fired with different phases relative to the HIFU, then upon averaging, the NIAD could be mitigated.     

声脉冲辐射力成像技术评价大鼠脂肪性肝炎的研究

目的探讨声脉冲辐射力成像(ARFI)技术无创评价大鼠脂肪性肝炎(NASH)的价值。方法将26只健康成年雄性无特定病原体级的SD大鼠分为对照组8只和脂肪肝组18只,根据不同喂养时间和单纯性脂肪肝(SS)、NASH诊断标准将脂肪肝组分为SS组9只和NASH组9只,分别行ARFI和CT检查,记录肝剪切波速度(SWV)和肝、脾CT值。实验到期后取其肝计算肝脏指数,并行病理分析。分析SWV值、CT值及肝脏指数与病理之间的关系,对SWV的诊断效率行ROC曲线分析,计算其敏感性和特异性。结果 SS组和NASH组肝SWV值分别为(1.01±0.02)m/s和(1.16±0.04)m/s,对照组肝SWV值(1.03±0.05)m/s,SS组与对照组间SWV值比较差异无统计学意义,SS组与NASH组间比较差异有统计意义(P﹤0.01)。SWV值与NASH有显著相关性(r=0.688)。应用SWV诊断NASH对应的ROC曲线下面积为0.91,SWV临界值为1.09 m/s,敏感性为85.7%,特异性为100%。结论 ARFI技术判断大鼠NASH有一定价值,且具有简便、无创的优势。     

声脉冲辐射力成像评价慢性肾功能不全价值

目的探讨声脉冲辐射力成像技术用于评价慢性肾功能不全的价值。方法采用声脉冲辐射力成像技术对84例慢性肾功能不全患者(肾功能不全组)和82例健康志愿者(对照组)进行检测,测量肾实质、肾窦、肾实质与肾窦交界处的剪切波速度,对检查结果进行对照分析。结果肾功能不全组肾实质、肾窦、肾实质与肾窦交界处剪切波速度高于对照组,差异有统计学意义(P<0.05);慢性肾功能不全Ⅰ期者剪切波速度与Ⅱ期者比较差异无统计学意义(P>0.05);Ⅰ、Ⅱ期者剪切波速度与Ⅲ、Ⅳ期者比较差异有统计学意义(P<0.05)。结论声脉冲辐射力成像技术可无创量化反映慢性肾功能不全及其程度。     

声辐射力冲击成像对乳腺结节性质的鉴别诊断价值

目的探讨应用声辐射力冲击成像(ARFI)技术对乳腺良性与恶性结节病灶的鉴别诊断价值。方法以33例<10 mm恶性乳腺结节患者及同期20例良性乳腺结节患者为研究对象,利用ARFI的声触诊组织成像(VTI)定性结节范围和声触诊组织定量(VTQ)量化结节的剪切波速度,与临床病理结果比较,分析良恶性病灶的ARFI-VTI和ARFI-VTQ参数差异。结果 ARFI-VTI能定性病灶结节范围,病灶结节在VTI图中与二维图中的面积比参数在良恶性组间差异有显著统计学意义,恶性组>1,良性组≤1(P<0.01);ARFI-VTQ测值在良恶性结节间差异有显著统计学意义,良性结节组VTQ剪切波速度为(2.67±1.63)m/s,恶性结节组VTQ剪切波速度为(5.24±2.72)m/s(P<0.01);对小结节型乳腺癌的诊断与病理诊断符合率为97.0%,特异度为80.0%。结论 ARFI检查对结节<10 mm的乳腺良恶性肿瘤具有鉴别诊断价值,值得临床应用推广。     

声辐射力脉冲成像对甲状腺小结节的诊断价值

目的探讨声辐射力脉冲成像(ARFI)对甲状腺小结节(<10 mm)良恶性的鉴别诊断价值。方法 78例甲状腺小结节患者,共95个直径<10 mm结节,对其行声触诊组织定性成像(VTI)和声触诊组织定量成像(VTQ)检查。结果甲状腺良性小结节57个,甲状腺微小癌38个。47个(82.5%)甲状腺良性小结节VTI成像模式为1级或2级,31个(81.6%)甲状腺癌表现为3级或4级,两者差异有统计学意义(P=0.000)。以VTI分级≥3级诊断为恶性结节,则VTI诊断敏感性、特异性、阳性预测值、阴性预测值及符合率分别为81.58%、82.46%、75.61%、87.04%、82.10%。甲状腺良性结节VTQ值(2.095±0.482)m/s,周边实质VTQ值(1.941±0.412)m/s,两者差异无统计学意义。恶性结节VTQ值(3.391±0.822)m/s,高于良性结节和周边甲状腺组织VTQ值(2.017±0.419),差异均有统计学意义(P<0.05)。以VTQ值2.785 m/s为分界点鉴别诊断甲状腺微小癌及良性小结节的敏感性、特异性及符合率分别为85.71%、85.24%、86.32%。结论 ARFI可从定性及定量两方面提供甲状腺小结节的弹性特征,有助于甲状腺小结节良恶性的鉴别诊断。     

声脉冲辐射力成像技术评价家兔肌肉损伤后组织修复的动态变化

目的 应用声脉冲辐射力成像(ARFI)技术观察家兔肌肉损伤后不同观察时间点肌肉组织修复的动态变化情况,并探讨其临床应用价值.方法 根据不同观察时间,将16只健康家兔随机分为4组,即损伤前和损伤后1d、7d、14d.用自制的重力锤建立兔肌肉损伤模型,应用ARFI观察腓肠肌声触诊组织定量(VTQ)测值的变化.实验结束后将兔处死,取肌肉组织行病理检查.结果 ARFI示肌肉损伤后各组VTQ值明显高于正常肌肉组织,差异均具有统计学意义(P＜0.01),损伤后1d、7d、14 d组间差异均具有统计学意义(P＜0.01).病理检查结果示损伤前肌纤维连续,未见明显肿胀、出血;损伤后1d,肌纤维断裂、明显肿胀、出血、充血;损伤后7d,肌细胞大面积坏死,大量的钙盐沉积;损伤后14d,大量的纤维细胞增生,钙盐沉积明显减少.超声弹性成像与病理结果相一致.结论 ARFI可直观、无创地评价肌肉损伤后不同时间点肌肉组织修复变化,为肌肉损伤后诊断和治疗提供客观依据.