JSUM ultrasound elastography practice guidelines: liver

In diffuse liver disease, it is extremely important to make an accurate diagnosis of liver fibrosis prior to determining indications for therapy or predicting treatment outcome and malignant potential. Although liver biopsy has long been the gold standard in the diagnosis of liver fibrosis, it is still an invasive method. In addition, the sampling error is an intrinsic problem of liver biopsy. Non-invasive serological methods for the diagnosis of liver fibrosis can be affected by factors unrelated to the liver. Recently, after the introduction of FibroScan, it became possible to measure liver fibrosis directly and non-invasively by elastography, which has attracted attention as a non-invasive imaging diagnostic tool for liver fibrosis. In addition, real-time tissue elastography is currently being used to conduct clinical trials at many institutions. Moreover, virtual touch quantification enables the observation of liver stiffness at any location by simply observing B-mode images. Furthermore, the recently developed ShearWave elastography visualizes liver stiffness on a color map. Elastography is thought to be useful for all types of diffuse liver diseases. Because of its association with portal hypertension and liver carcinogenesis, elastography is expected to function as a novel prognostic tool for liver disease. Although various elastographic devices have been developed by multiple companies, each device has its own measurement principle, method, and outcome, creating confusion in clinical settings. Therefore, it is extremely important to understand the characteristics of each device in advance. The objective of this guideline, which describes the characteristics of each device based on the latest knowledge, is for all users to be able to make the correct diagnosis of hepatic fibrosis by ultrasound elastography.     

Shear Wave Elastography for Evaluation of Liver Fibrosis

The prognosis and management of chronic viral hepatitis mainly depend on the extent of liver fibrosis, particularly in chronic hepatitis C. Liver histologic analysis is still considered the reference standard in the assessment of liver fibrosis despite the interobserver and interobserver variability in staging and some morbidity and mortality risks. Thus, noninvasive methods for assessing liver fibrosis are of great clinical interest. In the last decade, ultrasound‐based techniques to estimate the stage of liver fibrosis have become commercially available. They all have the capability to noninvasively evaluate differences in the elastic properties of soft tissues by measuring tissue behavior when a mechanical stress is applied. Shear wave elastography relies on the generation of shear waves determined by the displacement of tissues induced by the force of a focused ultrasound beam or by an external push. This article reviews the results that have been obtained with shear wave elastography for assessment of liver fibrosis.     

实时超声弹性成像诊断慢性肝病肝纤维化

目的探讨实时超声弹性成像(RTE)评价肝纤维化的价值。方法对88例慢性病毒性肝炎患者进行RTE扫查,测量肝组织/肋间肌肉组织的应变比。全部患者均接受经皮肝穿刺术并采集血清生化学指标,将应变比与实验室检测结果与肝纤维化病理分期进行对照。结果应变比与肝纤维化病理分期呈负相关(r=-0.82,P<0.01)。以肝明显纤维化(≥S2期)作为诊断标准,应变比的ROC曲线下面积为0.92,优于天门冬氨酸氨基转移酶/血小板比例指数(0.90)和Forns指数(0.84);以应变比1.10作为诊断肝明显纤维化的最佳诊断界值,其敏感度为86.84%,特异度为82.00%,阳性预测值为78.57%,阴性预测值为89.13%。结论 RTE可作为无创判断肝纤维化程度的新方法。     

Contemporary use of elastography in liver fibrosis and portal hypertension

The risk and speed of progression from fibrosis to compensated and decompensated cirrhosis define the prognosis in liver diseases. Therefore, early detection and preventive strategies affect outcomes. Patients with liver disease have traditionally been diagnosed at an advanced stage of disease, in part due to lack of non-invasive markers. Ultrasound elastography to measure liver stiffness can potentially change this paradigm. The purpose of this review was therefore to summarize advances in the field of ultrasound elastography with focus on diagnosis of liver fibrosis, cirrhosis and clinically significant portal hypertension, techniques and limitations. Four types of ultrasound elastography exist, but there is scarce evidence comparing the different techniques. The majority of experience concern transient elastography for diagnosing fibrosis and cirrhosis in patients with chronic viral hepatitis C. That said, the role of elastography in other aetiologies such as alcoholic- and non-alcoholic liver fibrosis still needs clarification. Although elastography can be used to diagnose liver fibrosis and cirrhosis, its true potential lies in the possibility of multiple, repeated measurements that allow for treatment surveillance, continuous risk stratification and monitoring of complications. As such, elastography may be a powerful tool for personalized medicine. While elastography is an exciting technique, the nature of ultrasound imaging limits its applicability, due to the risk of failures and unreliable results. Key factors that limit the applicability of liver stiffness measurements are as follows: liver vein congestion, cholestasis, a recent meal, inflammation, obesity, observer experience and ascites. The coming years will show whether elastography will be widely adapted in general care.     

实时剪切波弹性成像在诊断乙肝病毒肝纤维化患者中的价值

目的探讨实时剪切波弹性成像（SWE）诊断乙肝病毒（HBV）感染肝纤维化的价值及其影响因素。方法选取我院既往确诊的HBV感染肝纤维化患者137例作为纤维化组,选取同期HBV感染未出现肝纤维化的患者60例作为对照组,对比两组患者的SWE测定的肝脏弹性模量值,并根据不同的病理学纤维化程度分期进行分层分析;采用受试者工作曲线（ROC）分析SWE检测鉴别诊断肝纤维化患者的临床价值;采用Logistic回归方法分析影响SWE检测诊断肝纤维化的影响因素。结果纤维化组患者的肝脏弹性模量测定值高于对照组,差异具有统计学意义（P < 0.05）;不同病理学分期的肝纤维化患者肝脏弹性模量组间比较,差异具有统计学意义（P < 0.05）,S1~S4期肝脏弹性模量测定值逐渐增大;SWE测定肝脏纤维化值诊断肝纤维化的灵敏度为86.13%,特异度为85.00%,漏诊率为13.87%,误诊率为15.00%,ROC曲线下面积AUC值为0.889;Logistic回归模型分析显示,肝纤维化病理学分期越高、炎症分级越高与肝脏弹性模量值正确诊断肝纤维化呈正相关（P < 0.05）。结论SWE诊断HBV感染肝纤维化作为一种无创手段具有较高的灵敏度和特异度,但其诊断效能受到纤维化程度及炎症分级的影响。      

超声定量评估肝纤维化程度研究进展

肝纤维化程度的判断对于监测肝脏疾病的进展和监控药物疗效具有重要意义。作为肝纤维化分期金标准的肝活检因为有创操作,临床上不能广泛开展。而超声作为一种无创性的影像学技术,越来越多地被用于评价肝纤维化程度。本文对瞬时弹性成像技术、实时组织弹性成像技术、声脉冲辐射力弹性成像技术、实时剪切波弹性成像、组织结构声学定量技术,用于无创定量评估肝纤维化程度的研究进展进行综述。     

New diagnostic method for liver fibrosis and cirrhosis

Liver fibrosis, i.e. excessive accumulation of extracellular matrix proteins, occurs in most types of chronic liver diseases. The prognosis and management of chronic liver diseases depend on the degree of liver fibrosis. Therefore, the assessment of liver fibrosis provides useful information not only for diagnosis but also for treatment planning. Although liver biopsy is still the gold standard for assessing hepatic fibrosis, it has some technical limitations and risks. Furthermore, the dynamic process of liver fibrosis resulting from progression and regression cannot be quantified by liver biopsy. Therefore, alternative, simple, reliable and noninvasive tests are needed to assess the stage of fibrosis. Several noninvasive direct and indirect serum markers able to predict the presence of significant fibrosis or cirrhosis in patients with chronic liver disease with considerable accuracy have been reported. However, since most of these markers require complicated calculations, clinical application is difficult. Transient elastography (FibroScan) is a new method for the evaluation of liver stiffness. The technique is based on changes in tissue elasticity induced by hepatic fibrosis. Liver stiffness measured by transient elastography is a noninvasive, reproducible and reliable method to assess hepatic fibrosis as well as to diagnose liver cirrhosis. Based on accumulating clinical data, clinical applications of elastography will increase in the near future.     

超声弹性成像组织弥散定量分析技术在评估慢性肝病严重程度的临床应用研究

目的探讨超声实时弹性成像组织弥散定量分析技术对慢性肝病的诊断价值。方法正常组(21例)、肝纤维化组(57例)及肝硬化组(13例)三组患者均行超声实时弹性成像检查,并将所取得的12个组织弥散定量参数进行对照研究。结果 12个参数中除峰度(KURT)、相关性(CORR)外,三组间各数据比较差异均有统计学意义;除KURT外,其余参数与肝病严重程度之间有良好的相关性(P0.05),其中以应变均值(MEAN)、蓝色区域面积比(%AREA)及弹性指数(LF)相关系数最大,分别为-0.634、0.620、0.619;以%AREA、LF及MEAN区分正常组与肝纤维化组+肝硬化组的ROC曲线下面积分别为0.830、0.813、0.832;区分正常组+肝纤维化组与肝硬化组的曲线下面积分别为0.910、0.936、0.928。结论超声实时弹性成像检查有助于区分正常组、肝纤维化组及肝硬化组患者,其中以MEAN、LF及%AREA与慢性肝病的严重程度相关性最高,对区分慢性肝病各阶段方面有较好的诊断价值。     

Measurement of Liver Stiffness Using Shear Wave Elastography in a Rat Model: Factors Impacting Stiffness Measurement with Multiple- and Single-Tracking-Location Techniques

The clinical use of elastography for monitoring fibrosis progression is challenged by the subtle changes in liver stiffness associated with early-stage fibrosis and the comparatively large variance in stiffness estimates provided by elastography. Single-tracking-location (STL) shear wave elasticity imaging (SWEI) is an ultrasound elastography technique previously found to provide improved estimate precision compared with multiple-tracking-location (MTL) SWEI. Because of the improved precision, it is reasonable to expect that STL-SWEI would provide improved ability to differentiate liver fibrosis stage compared with MTL-SWEI. However, this expectation has not been previously challenged rigorously. In this work, the performance of STL- and MTL-SWEI in the setting of a rat model of liver fibrosis is characterized, and the advantages of STL-SWEI in staging fibrosis are explored. The purpose of this study was to determine what advantages, if any, arise from using STL-SWEI instead of MTL-SWEI in the characterization of fibrotic liver. Thus, the ability of STL-SWEI to differentiate livers at various METAVIR fibrosis scores, for ex vivo postmortem measurements, is explored. In addition, we examined the effect of the common confounding factor of fluid versus solid boundary conditions in SWEI experiments. Sprague-Dawley rats were treated with carbon tetrachloride over several weeks to produce liver disease of varying severity. STL and MTL stiffness measurements were performed ex vivo and compared with the METAVIR scores from histological analysis and the duration of treatment. A strong association was observed between liver stiffness and weeks of treatment with the liver toxin carbon tetrachloride. Direct comparison of STL- and MTL-SWEI measurements revealed no significant difference in ability to differentiate fibrosis stages based on SWEI mean values. However, image interquartile range was greatly improved in the case of STL-SWEI, compared with MTL-SWEI, at small beam spacing.     

Quantification of Liver Viscoelasticity with Acoustic Radiation Force: A Study of Hepatic Fibrosis in a Rat Model

Ultrasound elastography, based on shear wave propagation, enables the quantitative and non-invasive assessment of liver mechanical properties such as stiffness and has been found to be feasible for and useful in the diagnosis of hepatic fibrosis. Most ultrasound elastographic methods use a purely elastic model to describe liver mechanical properties. However, to describe tissue that is dispersive and to obtain an accurate measure of tissue elasticity, the viscoelasticity of the tissue should be examined. The objective of this study was to investigate the shear viscoelastic characteristics, as measured by ultrasound elastography, of liver fibrosis in a rat model and to evaluate the diagnostic accuracy of viscoelasticity for staging liver fibrosis. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl₄); 6 rats served as controls. Liver viscoelasticity was measured in vitro using shear waves induced by acoustic radiation force. The measured mean values of liver elasticity and viscosity ranged from 0.84 to 3.45 kPa and from 1.12 to 2.06 Pa·s for fibrosis stages F0–F4, respectively. Spearman correlation coefficients indicated that stage of fibrosis was well correlated with elasticity (0.88) and moderately correlated with viscosity (0.66). The areas under receiver operating characteristic curves were 0.97 (≥F2), 0.91 (≥F3) and 1.00 (F4) for elasticity and 0.91 (≥F2), 0.79 (≥F3) and 0.74 (F4) for viscosity, respectively. The results confirmed that shear wave velocity was dispersive in frequency, suggesting a viscoelastic model to describe liver fibrosis. The study finds that although viscosity is not as good as elasticity for staging fibrosis, it is important to consider viscosity to make an accurate estimation of elasticity; it may also provide other mechanical insights into liver tissues.     

声辐射力脉冲成像定量评价非酒精性脂肪性肝病与病理对照研究

目的 本研究应用声脉冲辐射力成像技术(ARFI)对非酒精性脂肪性肝病(NAFLD)患者进行检测和分析,探讨该技术在无创定量评价NAFLD的临床应用价值.方法 对67例NAFLD患者应用ARFI技术对肝脏的实时超声弹性进行测量,所有患者均进行超声引导下肝脏穿刺活检,以病理结果为金标准,对肝脏的ARFI测值与肝脏脂肪变性、小叶内炎症及肝纤维化程度关系进行统计分析.结果 NAFLD患者不同脂肪变性和小叶内炎症程度间ARFI测值差异无统计学意义(P>0.05),肝纤维化分期为S0~S4期的ARFI测值分别为(1.18±0.28)m/s,(1.25±0.31)m/s,(1.44±0.52)m/s,(1.54±0.50)m/s和(1.86±0.73)m/s,组间比较差异具有统计学意义(P<0.05).肝脏ARFI测值与肝纤维化分期存在相关性,相关系数为0.42(P<0.001).ARFI技术诊断NAFLD肝纤维化S≥1,S≥2,S≥3和S=4的受试者工作特征曲线下面积分别为0.631、0.714、0.765和0.853.结论 声脉冲辐射力成像技术作为一种实时超声弹性成像技术,可较准确的无创定量评价NAFLD肝纤维化程度,具有良好的临床应用前景.     

实时剪切波弹性成像评价肾纤维化进展

肾纤维化是慢性肾病病程中的病理变化,为终末期肾病的病理表现。实时评估肾纤维化程度可协助临床及时调整治疗方案。实时剪切波弹性成像可根据肾组织硬度评估肾脏病变程度。本文对实时剪切波弹性成像评估肾纤维化的应用进展进行综述。     

超声弹性成像在肝纤维化分期中的应用研究

目的 探讨超声弹性成像(RTE)在肝纤维化分期中的应用价值.方法 选择不同病理分期的肝纤维化患者224例,应用RTE评分标准将患者分级,对比其与病理检查分期的相关性,并界定肝纤维化与肝硬化的RTE评级的分界点.结果 肝脏RTE分级为F0、F1、F2级的患者,病理分期多为纤维化(S0、S1、S2、S3)(P<0.05);RTE分级为F4级的患者,病理分期多为肝硬化(S4)(P<0.05);RTE分级为F3时,病理分期分布差异无统计学意义(P>0.05).RTE评分方法与病理分期方法在评价肝纤维化程度时有较高的一致性(Kappa值=0.816).结论 RTE可作为较客观地评价肝纤维化分期的辅助检查方法;此外,乃级可认为是肝纤维化与肝硬化分界点.     

Comparison of Sound Touch Elastography,Shear Wave Elastography and Vibration-Controlled Transient Elastography in Chronic Liver Disease Assessment using Liver Biopsy as the “Reference Standard”

Chronic liver disease (CLD) is currently a major cause of death. Ultrasound elastography (USE) is an imaging method that has been developed for CLD assessment. Our aim in the study described here was to evaluate and compare a new commercial variant of USE, sound touch elastography (STE), with already established USE methods, shear wave elastography (SWE) and vibration-controlled transient elastography (VCTE), using liver biopsy as the “reference standard.” For our study, 139 consecutive patients underwent standard liver STE, SWE and VCTE examinations with the corresponding ultrasound devices. A receiver operator characteristic (ROC) curve analysis was performed on the stiffness values measured with each method. ROC analysis revealed, for SWE, STE and VCTE, areas under the ROC curve of 0.9397, 0.9224 and 0.9348 for fibrosis stage (F), F ≥ F1; 0.9481, 0.9346 and 0.9415 for F ≥ F2; 0.9623, 0.9591 and 0.9631 for F ≥ F3; and 0.9581, 0.9541 and 0.9632 for F = F4, respectively. In conclusion, STE performs similarly to SWE and VCTE in CLD stage differentiation.     

肝脏剪切波弹性成像影响因素的研究进展

剪切波弹性成像可通过探测组织内剪切波传播速度定量反映组织硬度,可用于无创评估肝纤维化。纤维化程度被认为是影响肝脏弹性的重要影响因素,但随着研究的深入,发现还有诸多因素对肝脏弹性测值准确性有影响。本文对炎症、脂肪肝、胆汁淤积、肝脏淤血、进食、呼吸、肥大细胞增多症、性别和年龄、测量深度和次数对肝脏剪切波弹性成像的影响进行综述。     

Prospective Comparison of the Diagnostic Performance of Magnetic Resonance Elastography with Acoustic Radiation Force Impulse Elastography for Pre-operative Staging of Hepatic Fibrosis in Patients with Hepatocellular Carcinoma

The purpose of this study was to compare the diagnostic accuracy of magnetic resonance (MR) elastography with that of acoustic radiation force impulse (ARFI) elastography for pre-operative staging of hepatic fibrosis in patients with hepatocellular carcinoma. We prospectively enrolled 77 patients who were scheduled to undergo hepatectomy for hepatocellular carcinoma. Pre-operative MRE and ARFI elastography examinations were performed on the same day, and liver stiffness/velocity values were determined. Fibrosis stage and necro-inflammatory activity of resected specimens were determined histopathologically using the METAVIR scoring system. Correlations between MRE and ARFI elastography findings and histologic findings were determined by receiver operating characteristic (ROC) analysis. Correlation of MRE was excellent and correlation of ARFI elastography was good with fibrosis stage. MRE had better diagnostic performance than ARFI elastography in estimating substantial fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4). The optimal cutoff value and the area under the ROC curve (AUROC) were determined using ROC curve analysis. The highest Youden index was used as a criterion for selecting the optimal cutoff value. ROC analysis revealed that MRE discriminated advanced stages of fibrosis (F?≥?2) well in patients with hepatocellular carcinoma at a cutoff value of 3.0?kPa with an AUROC value of 0.93, and ARFI elastography did so at a cutoff value of 1.77?m/s with an AUROC value of 0.81 for predicting advanced stages of fibrosis (F?≥?2). In conclusion, MRE is a more accurate imaging modality than ARFI elastography in estimating advanced stages of fibrosis and cirrhosis.     

超声实时组织弹性成像在甲状腺弥漫性疾病中的初步应用

目的 探讨超声实时组织弹性成像对甲状腺弥漫性疾病的诊断价值.方法 采用主成分分析对123例甲状腺弥漫性疾病患者和42例甲状腺正常者的11个弹性定量参数进行综合分析,把综合评价函数值命名为硬度指数(stiffness index,SI)来反映甲状腺疾病组织的弹性信息,并用方差分析比较SI在各组间的差异.结果 慢性淋巴细胞性甲状腺炎SI为 86.37±20.45,亚急性甲状腺炎SI为 86.14±19.95,原发性甲状腺功能亢进SI为 54.68±21.69,正常对照组SI为 41.34±15.59.慢性淋巴细胞性甲状腺炎、亚急性甲状腺炎、原发性甲亢与正常对照组之间SI差异有统计学意义(P<0.05);原发性甲亢与慢性淋巴细胞性甲状腺炎、亚急性甲状腺炎之间的SI差异有统计学意义(P<0.05);慢性淋巴细胞性甲状腺炎与亚急性甲状腺炎之间SI差异无统计学意义(P>0.05).结论 实时超声弹性成像可间接反映甲状腺病变组织的硬度,对甲状腺弥漫性疾病具有一定的诊断价值.

Abstract：

Objective To explore the diagnosis value of ultrasound real-time elastography in thyroid diffuse diseases.Methods Eleven elastic quantitative parameters of 123 patients with thyroid diffuse diseases and 42 healthy volunteers obtained from the ultrasound real-time elastography were analyzed with principal components analysis to attain a comprehensive evaluation value which was named stiffness index(SI),reflecting the organization elastic information of different thyroid diffuse diseases.SI among each group was compared by ANOVA.Results Chronic lymphocytic thyroiditis SI was 86.37±20.45,subacute thyroiditis SI was 86.14±19.95,primary hyperthyroidism SI was 54.68±21.69,normal control group SI was 41.34±15.59,respectively.The SI between chronic lymphocytic thyroiditis,subacute thyroiditis,primary hyperthyroidism and normal controls had significant statistical differences (P<0.05),the SI between primary hyperthyroidism and chronic lymphocytic thyroiditis,subacute thyroiditis had significant statistical differences (P<0.05),the SI between chronic lymphocytic thyroiditis and subacute thyroiditis had no significant statistical difference (P>0.05).Conclusions Ultrasound real-time elastography could indirectly reflect the stiffness information of thyroid lension tissue and have a certain degree of diagnosis value in thyroid diffuse disease.     

超声弹性成像评价肝纤维化程度的研究现状

肝脏活检是评估肝纤维化的金标准,但其有创且有出血等并发症的发生,限制其广泛应用。而超声弹性成像技术能检测肝脏的物理弹性数据,以此分析纤维化程度。本文介绍目前临床上常用的3种超声弹性成像技术,即实时弹性成像、瞬间弹性成像、声脉冲辐射力成像在肝纤维化诊断中的研究现状及新进展。     

Elastography assessment in patients with chronic HCV infection

Introduction: Liver fibrosis (LB) assessment plays an important role in hepatology. A common characteristic of all chronic liver diseases is the occurrence and progression of fibrosis towards cirrhosis. Besides its plain interest for prognosis purposes, determining the fibrosis reveals the natural history of the disease and the risk factors associated with its progression to guide the antifibrotic action of different treatments. Discussion: Today, in clinical practice there are three available methods for the evaluation of LB. Biopsy, which is still considered as the ‘gold standard’ method. Serological markers and their mathematical combination are suggested in the last years in alternative to LB. More recently, transient elastography (TE) was proposed. TE is a simple and noninvasive method for measuring liver stiffness. This technique is based on the progression speed of an elastic shear wave within the liver. Conclusions: Currently, there are just a few studies capable of evaluating the TE effectiveness in chronic liver diseases, mainly in patients infected with hepatitis C virus (HCV). Its application must also be studied in the monitoring of patients suffering from chronic HCV infection and subjected to a treatment that can modify their degree of liver fibrosis. The results of TE must be interpreted according to the clinical background of the specialist.     

Liver Fibrosis Assessment Using Transient Elastography Guided with Real-Time B-mode Ultrasound Imaging: A Feasibility Study

Liver fibrosis is a kind of chronic damage of the liver and can lead to cirrhosis, one of the top 10 causes of death in the Western world. However, there is still a lack of noninvasive methods for diagnosing liver fibrosis. Fibroscan (Echosens, Paris, France), a device based on A-mode transient elastography, has shown promising results. In this study, a transient elastography system with real-time B-mode imaging for non-invasive liver fibrosis assessment, named Liverscan, was developed; its performance was tested and compared with that of the Fibroscan. A specific measurement probe was designed and fabricated with a B-mode ultrasound transducer fixed along the axis of a mechanical vibrator. It was integrated with the Liverscan to measure liver stiffness based on the shear wave propagation in liver tissues. The system was validated by mechanical indentation test using custom-made agar-gelatin phantoms with different stiffness. To further test its feasibility, in vivo measurements were conducted in 67 volunteers (age, 34 ± 3 years; body mass index, 21.3 ± 2.8 kg/m²; Mean ± SD., 34 male and 33 female), including 20 patients with various liver diseases, and 28 (19 male and 9 female) being tested by both Liverscan and Fibroscan. A significant linear correlation between the stiffness measured by the mechanical indentation test and that by the Liverscan (r = 0.973; p < 0.001) was obtained. The in vivo liver stiffness measured by Liverscan was also correlated with that by Fibroscan significantly (r = 0.886; p < 0.001). There was a significant difference in liver stiffness between the 20 patients and the other healthy subjects (14.1 ± 3.4 kPa vs. 10.5 ± 2.1 kPa; p = 0.001). The intra- and inter-observer tests indicated that the measurements were repeatable with intra-class correlation coefficients being 0.987 (p < 0.001) and 0.988 (p < 0.001), respectively. This study demonstrated that Liverscan with a specifically designed probe was able to measure and differentiate liver of different stiffness using the established measurement protocol under the guidance of real-time B-mode ultrasound imaging.