Imaging of malignant liver masses: characterization and detection

Noninvasive characterization of focal liver lesions is largely based on their enhancement patterns on contrast-enhanced imaging. The use of microbubble contrast agents combined with specialized ultrasound (US) techniques has significantly expanded the role of US in the diagnosis of focal liver lesions based on their vascularity and specific enhancement features. With the advantage of real-time scanning, contrast-enhanced ultrasound (CEUS) can evaluate small lesions that are indeterminate on computed tomography (CT) or magnetic resonance imaging (MR), because CEUS is far less affected by timing issues. Hepatocellular carcinoma is typically characterized by increased arterial flow with frequent dysmorphic tumor vessels and decreased portal venous flow. However, negative enhancement in the portal phase is often not obvious until late (>2 minutes). On the other hand, metastasis shows prompt brief arterial hypervascularity, with either a rim or diffuse pattern and rapid washout, seen as perfusion defects during the portal venous phase. This pattern of complete rapid washout of metastases within the homogeneously enhanced background liver parenchyma can improve their detection and also improve differentiation from hepatocellular carcinoma or benign focal lesions. All malignant lesions generally show negative enhancement or washout during the extended portal venous phase, and this pattern is useful to differentiate them from benign lesions. Microbubble agents, confined to the intravascular space, may infrequently characterize malignancy by showing washout whereas CT or MR shows persistent enhancement due to interstitial distribution.     

The current status of contrast-enhanced ultrasound in China

This review article provides an overview of the use of contrast-enhanced ultrasound (CEUS) in China. Currently, the only licensed contrast agent is SonoVue, a sulfur hexafluoride-filled microbubble contrast agent. In combination with a low mechanical index contrast-specific imaging mode, SonoVue-enhanced CEUS can be used to visualize the micro and macro-vasculature continuously. Since 2004, CEUS has been widely used in China in various clinical scenarios. The authors compared CEUS with baseline ultrasound or contrast-enhanced computed tomography with regard to characterization of focal liver lesions (FLLs). On CEUS, heterogeneous or homogeneous hyperenhancement during the arterial phase and washout in the portal/late phase are typical findings for hepatocellular carcinoma. The enhancement features of intrahepatic cholangiocarcinoma, infected FLLs, focal fatty infiltration, focal fatty sparing, complex cystic FLLs, and uncommon benign FLLs were carefully depicted. CEUS was also used for patient selection in ablation therapy and evaluation of response to ablation for liver cancer. The utility of three-dimensional CEUS of the liver was also explored. In non-liver use, CEUS in hilar cholangiocarcinoma, gallbladder, breast, and prostate was initially investigated. In addition, CEUS was used in interventional procedures such as CEUS-guided hemostatic injection, intraoperative CEUS in neurosurgery, and evaluation of response to high-intensity focused ultrasound ablation of uterine fibroids. The Chinese experience has resulted in increased use of CEUS.     

Real-time contrast-enhanced ultrasound imaging of infected focal liver lesions.

OBJECTIVE: The purpose of this study was to investigate the features of infected focal liver lesions on contrast-enhanced ultrasound (CEUS) imaging. METHODS: Thirty-two hepatic abscesses, 15 infected granulomas, and 6 inflammatory pseudotumors in 53 patients were evaluated with real-time CEUS before awareness of the definitive diagnosis. A 2.4-mL dose of a sulfur hexafluoride-filled microbubble contrast agent was administered by intravenous bolus injection. RESULTS: The numbers of abscesses with hyperenhancement, isoenhancement, and hypoenhancement in the arterial phase were 26 (81.3%), 5 (15.6%), and 1 (3.1%), respectively. Thirty (93.8%) lesions were irregularly rim enhanced with nonenhanced areas; enhanced septa were shown in 22 (68.8%) lesions; and transient hyperenhancement of liver parenchyma around the lesion was shown in 20 (62.5%). In 31 abscesses with hyperenhancement or isoenhancement in the arterial phase, 25 (80.6%) showed contrast wash-out and changed in appearance to hypoenhancement in the late phase. As for infected granulomas and inflammatory pseudotumors, 16 (76.2%) lesions showed hyperenhancement or isoenhancement in the arterial phase, and all of them were hypoenhanced in the portal and late phases. CONCLUSIONS: Most infected focal liver lesions showed more rapid contrast wash-out than the surrounding liver parenchyma, which is similar to malignant lesions. Abscesses typically showed features of rim enhancement, enhanced internal septa, nonenhanced central necrotic areas, and transient hyperenhanced liver parenchyma around the lesions. The CEUS appearance of infected granulomas and inflammatory pseudotumors was variable, and a biopsy was necessary for definitive diagnosis.     

超声造影与增强螺旋CT诊断肝硬化背景下≤2 cm结节样病灶的比较研究

目的 探讨超声造影(contrast-enhanced ultrasound,CEUS)与增强螺旋CT(contrast-enhanced helical computed tomography,CECT)对肝硬化背景下≤2 cm结节样病灶的诊断效能.方法 对72例81个肝硬化背景下常规超声检查可疑肝内小占化病变者(最大直径≤2 cm)进行CEUS和CECT检查(两者间隔时间≤2周),将两种检查的术前诊断与病理结果进行比较分析,评估两种检查方法的诊断效能.结果 81个病灶53个为肝细胞癌(HCC),26个增生结节,2个血管瘤.53个HCC中,CEUS 51个(96.2%)病灶动脉期呈高增强,CECT 41个(77.4%)病灶动脉期显示强化,CEUS与CECT在显示动脉期血供方面差异有统计学意义(P<0.01).以病灶动脉期呈高增强,门脉期或延迟期消退为低增强作为诊断HCC的标准,CEUS诊断小结节样病灶的敏感性、特异性、准确性分别为86.8%、82.1%、85.2%.CECT分别为73.6%、92.9%、80.2%(P>0.05).结论 CEUS对≤2 cm HCC动脉期血供的显示率高于CECT,CEUS对肝硬化背景下小结节样病灶的诊断能力与CECTT相似.     

肝脏局灶性病变MR动态增强扫描的临床应用

目的：探讨肝脏局灶性疾病ＭＲ动态增强扫描的方法和临床应用。方法：回顾性分析６８例肝脏局灶性病变：包括原发性肝细胞癌２４例,周围型肝管细胞癌２例,转移瘤１６例,海绵状血管瘤２４例,局灶性结节增生２例。     

肝局灶性病变超声造影诊断指标初探

目的 探讨适宜中国肝局灶性病变的超声造影诊断指标。方法 以注射造影剂后肝动脉开始显影作为动脉相的起始时间，以门静脉开始显影作为门脉相起始时间，以肝实质增强达峰值为实质相起始时间；分析682例肝局灶性病变超声造影肝动脉、门静脉的始增时间及肝实质的增强峰值时间、肝内病灶的开始减退时间，分析增强模式。结果 肝硬化与非肝硬化组肝动脉、门静脉及肝实质始增时间有显著差异，肝内良恶性病灶增强退出时间有显著差异。85％的原发性肝癌及99％肝转移癌在注射造影剂后180s内退出，故以180s作为延迟相起始时间及与实质相的划分点，由此将超声造影分为四个时相。结论 由于肝背景不同造成血流动力学差异，病灶增强时相以自身背景对比更为适宜；根据新的时相定义及病灶增强退出特征，总结出中国人肝癌及其他肝局灶性病变的超声造影诊断标准。     

超声造影对Budd-Chiari综合征合并肝脏局灶性结节的鉴别诊断价值

目的 探讨Budd-Chiari综合征(BCS)合并肝脏局灶性结节的超声造影鉴别诊断要点.方法 回顾性分析36例BCS合并肝局灶性结节患者的常规超声及超声造影图像,并结合临床病理检查和增强CT及MRI成像等其他影像学检查资料分析.结果 36例BCS患者中11例合并肝癌结节,25例合并增生结节.其中BCS合并肝癌结节超声造影模式为典型的"快进快出",BCS合并增生结节的超声造影表现是多样化的,可分为3型.Ⅰ型增生结节超声造影3个时相与周围肝实质相比均呈等增强;Ⅱ型和Ⅲ型虽然造影特点不同,Ⅱ型动脉相呈离心性增强,Ⅲ型动脉相呈环状向心性增强,但延迟相均较周围肝实质呈等增强或部分高增强.结论 BCS合并肝脏局灶性结节超声造影表现呈多样化,超声造影对鉴别结节良恶性有重要价值.     

灰阶超声影像组学与超声造影鉴别诊断肝脏局灶性病变良恶性的对比研究

目的 对比分析灰阶超声影像组学与超声造影对肝脏局灶性病变（FLLs）良恶性的鉴别诊断价值。方法 选取我院经手术病理证实的162例FLLs患者,其中恶性86例,良性76例,均行灰阶超声及超声造影检查,比较两者声像图表现的差异。162例FLLs患者随机按照7∶3比例分为训练组113例和验证组49例,比较两组灰阶超声影像组学参数,包括形态学特征、直方图特征、灰度区域大小矩阵特征、Haralick特征、灰度共生矩阵特征、灰度游程矩阵特征,筛选有意义的非冗余特征,选择最优特征子集构建灰阶超声影像组学模型,绘制受试者工作特征曲线分析其鉴别诊断FLLs良恶性的效能。结果 恶性病灶超声造影多表现为动脉相病灶呈高增强,门脉相病灶呈低增强,且两者间存在明显分界（67例）;良性病灶超声造影均表现为动脉相病灶呈等增强或稍高增强,造影剂从病灶周边缓慢向中心灌注,门脉相及延迟相病灶均呈等增强或高增强,未见明显的造影剂消退现象。训练组和验证组良恶性病灶直方图特征、灰度共生矩阵特征、灰度游程矩阵特征比较差异均有统计学意义（均P<0.05）;最终纳入1个直方图特征、1个灰度共生矩阵特征、1个灰阶游程矩阵特征构建灰...     

肝内胆管细胞癌超声造影与增强MRI表现对比分析

目的 分析肝内胆管细胞癌超声造影与增强MRI影像学表现特点.方法 8例经手术病理证实的肝内胆管细胞癌,术前行超声造影、增强MRI检查.结果 超声造影：动脉期5例周边环状高增强,1例整体均匀高增强,2例整体不均匀高增强;门脉期6例整体为低增强,2例内部呈低增强,周边仍见环状高增强;延迟期均呈低增强.增强MRI：动脉期8例环状高增强;门脉期及延迟期1例环状高增强,7例向心性增强.结论 肝内胆管细胞癌超声造影与增强MRI表现不同,可能与疾病的病理特点及两种造影剂在人体内的分布特点有关.     

Analysis of different contrast enhancement patterns after microbubble-based contrast agent injection in liver hemangiomas with atypical appearance on baseline scan

Background We describe different possible enhancement patterns in liver hemangiomas with atypical appearance on baseline ultrasound after microbubble-based contrast agent injection. Methods From a series of 253 consecutive lesions that were indeterminate on baseline ultrasound and then scanned after injection of air-filled microbubble contrast agent, 65 focal liver lesions were retrospectively selected on the basis of a diagnosis of liver hemangioma on multiphase contrast-enhanced computed tomography (n = 23), magnetic resonance imaging (n = 27), or histology (n = 15). Each lesion was scanned during arterial phase (30 s after microbubble injection) and late phase (5 min after injection). On-site sonologists performed retrospective assessment of contrast-enhancement patterns by consensus. Results Centripetal fill-in preceded (n = 50) or not preceded (n = 3) by peripheral nodular/rim-like enhancement was the prevalently observed contrast-enhancement pattern, equivalent to the typical enhancement pattern of liver hemangiomas on contrast-enhanced computed tomography or magnetic resonance imaging. In the remaining lesions, additional enhancement patterns (diffuse contrast enhancement with rapid fill-in and a late hyper-isoechoic appearance, n = 6; peripheral nodular enhancement with a late hypoechoic appearance, n = 3; or persistent heterogeneous and hyperechoic appearance, n = 3) were observed. Conclusion Different contrast-enhancement patterns are possible in atypical liver hemangiomas after microbubble injection. Typical centripetal fill-in is the prevalent pattern and its evidence allows diagnosis.     

SonoVue超声造影在肝良性占位病变诊断中的应用

目的探讨超声造影在肝良性占位病变诊断中的应用。方法30例肝良性占位病变患者经肘部静脉团注SonoVue。采用超声造影二次谐波成像技术,实时观察注射造影剂后病灶增强特征。结果经超声造影后,23个肝血管瘤动脉相均呈高回声增强,20个(87%)表现为周边向心型,2个(8.7%)为中央扩散型,1个(4.3%)为整体型增强特征,20个病灶在门脉相和延迟相仍为高回声增强,2个病灶渐变为等回声增强,1个病灶渐变为低回声增强。2个肝局灶性结节增生病灶在动脉相均呈中央扩散型增强,表现为轮辐状,门脉相及延迟相呈等回声增强。3个肝局部脂肪缺失病灶均显示动脉相无增强,门脉相及延迟相呈等回声。2个肝脓肿病灶动脉相周边无增强,延迟相病灶内呈低回声增强及无增强。结论SonoVue超声造影二次谐波成像技术能动态显示病灶增强特征,有助于肝良性占位病变的诊断及鉴别诊断。     

Evidence of diagnostic enhancement pattern in hepatocellular carcinoma nodules ≤2 cm according to the AASLD/EASL revised criteria

Purpose

To define the percentage of small (≤2 cm) hepatocellular carcinoma (HCC) nodules showing the diagnostic enhancement pattern at CEUS, computed tomography (CT), and gadobenate dimeglumine (Gd-BOPTA)—enhanced magnetic resonance (MR) imaging.

Methods

42 cirrhotic patients (26 male, 16 female; 67 ± 12 years) with 46 biopsy-proven HCCs ≤2 cm were included. Each HCC was scanned by CEUS, contrast-enhanced CT, and Gd-BOPTA-enhanced MR imaging. Nodule enhancement was evaluated by two readers. Independent analysis was followed by consensual analysis and the proportion of HCCs with the diagnostic enhancement pattern (nodule hyperenhancing on hepatic arterial phase and hypoenhancing on portal venous—late phase) on CEUS, CT, and MR imaging was compared by chi-square test.

Results

Very good inter-reader agreement was observed on hepatic arterial phase and portal venous—late phase: CEUS, k = 0.89 and 0.85; CT, k = 0.91 and 0.88; MR imaging, k = 0.96 and 0.94. CEUS and CT did not differ in the percentage of HCC nodules with a diagnostic enhancement pattern (18/46 and 16/46; P = 0.66), while MR imaging revealed the diagnostic pattern in higher percentage of nodules (29/46; P = 0.012) in comparison to CEUS and CT.

Conclusions

CEUS and contrast-enhanced CT did not differ in the percentage of small HCC nodules with diagnostic enhancement pattern, while Gd-BOPTA-enhanced MR imaging revealed the diagnostic pattern in a higher nodule number in comparison to CEUS and CT.     

Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has expanded the role of US in the diagnosis of liver nodules in high risk patients for hepatocellular carcinoma (HCC). HCC is typically characterized by arterial hypervascularity and later washout (negative enhancement). Washout in the portal phase is often not obvious until late (>90 s). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial and portal venous phases. However, there are occasional cases with overlap of imaging features between benign and malignant nodules, including hypovascular HCC and hypervascular HCC without washout. CEUS is helpful to characterize potential mimickers of HCC on imaging such as nontumorous arterioportal shunt or hemangioma. CEUS is also useful for a guidance of percutaneous local therapy of HCC and post-procedure monitoring of therapeutic response. CEUS can be effectively used in the diagnostic algorithm of small (1–2 cm) newly detected nodules during HCC surveillance.     

实时灰阶超声造影评价肝移植术前门脉系统栓子的价值

目的探讨实时灰阶超声造影在肝移植术前门脉系统栓子诊断及良恶性鉴别诊断中的价值。方法应用SonoVue造影剂及对比脉冲序列（CPS）技术对37例肝移植术前门脉系统栓子患者,共84条血管进行低机械指数实时灰阶超声造影检查。结果经过肝移植手术或螺旋CT门静脉成像证实,78条血管栓子形成（瘤栓50个,血栓28个）,6条血管通畅。超声造影诊断门脉系统栓子的敏感性98.7%,特异性100%,以栓子内动脉相早期造影剂灌注为标准,诊断门脉系统瘤栓的敏感性100%,特异性100%。结论实时灰阶超声造影可评价肝移植术前门脉系统的通畅性,提高栓子的检出率,并可鉴别栓子的良恶性,为肝移植手术方案的确定提供重要准确的信息。     

超声造影诊断肝局灶性病变在县市级医院的应用

目的探讨超声造影对肝脏局灶性病变的诊断价值以及超声造影技术在县市级医院的可行性。方法125例常规超声检查不能完全明确诊断的肝脏局灶性病变患者，采用造影剂SonoVue进行超声造影。分析研究不同性质的肝脏局灶性病变在不同时相的增强表现。结果不同性质的肝脏局灶性病变都有其特征性的增强模式．从而有助于鉴别诊断。与增强CT或增强MRI对照，大多数病灶有相似的增强变化规律。超声造影的诊断准确率达到94．4％（118／125）。结论超声造影技术可明显提高对肝脏局灶性病变的诊断水平，而且在县市级医院开展此技术是可行的。     

肝硬化背景下肝局灶性小病变超声造影诊断价值

目的探讨超声造影对肝硬化背景下肝局灶性小病变的诊断价值。方法采用造影剂SonoVue和低机械指数超声造影,观察33例肝硬化背景下吖疑肝局灶性病变40个病灶不同时相的增强表现。结果恶性病变超声造影表现为动脉相呈高增强,门脉相呈等或低增强,延迟相呈低增强;良性病变超声造影表现为门脉相和延迟相出现持续增强,动脉相无增强。本组超声造影诊断准确率97．5％,假阴性5．26％。结论超声造影能提高肝硬化背景下小肝癌的诊断率。     

彩色多普勒超声检查、超声造影、增强CT诊断肝脏局灶性结节样增生的比较

目的探讨肝脏局灶性结节样增生(FNH)的彩色多普勒超声检查、超声造影、增强CT表现及其诊断价值。方法 2006～2009年经手术及病理证实的10例FNH患者共14个病灶均行彩色多普勒超声检查,其中8个病灶行超声造影检查,4个病灶行增强CT检查。结果 14个病灶中,彩色多普勒超声检查显示5个病灶(5/14,35.71%)内有轮辐状血流信号,最大血流速度平均为(0.59±0.19)m/s,阻力指数平均为0.46±0.16。超声造影显示5个病灶(5/8,62.50%)出现动脉期早期迅速全瘤强化,其他3个病灶(3/8,37.50%)呈轮辐状离心性快速强化,门脉期及延迟期回声稍高于肝实质或与肝实质等回声,有2个病灶(2/8,25.00%)于延迟期见低回声中央星状瘢痕。增强CT显示4个病灶平扫均呈低密度,动脉期显著均匀性强化,门脉期强化接近于肝实质密度,有2个病灶(2/4,50.00%)于动脉期及门脉期见低密度星状瘢痕。结论彩色多普勒超声、超声造影、增强CT这3种方法结合可大大提高FNH的确诊率。     

Liver metastases in cancer: detection with contrast-enhanced ultrasonography

In patients with known or suspected malignancy, ultrasonography (US) is often the first choice for liver imaging because of its widespread availability and low cost. Compared with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), the sensitivity of conventional US for detecting hepatic metastases is relatively poor. The advent of microbubble contrast agents changed this situation. Sensitivity and specificity increased substantially with the use of these contrast agents and contrast-specific imaging modes in recent years. Currently, numerous US imaging methods exist, based on Doppler techniques or harmonic imaging. They exploit the complex nonlinear behavior of microbubbles in a sound field to achieve marked augmentation of the US signal. Although microbubble contrast agents are essentially blood pool agents, some have a hepatosplenic specific late phase. Imaging during this late phase is particularly useful for improving the detection of malignant liver lesions and allows US to perform similarly to spiral CT as shown by recent studies. In addition, this late phase imaging is very helpful for lesion characterization. Low mechanical index imaging with the newer perfluor agents permits real-time imaging of the dynamic contrast behavior during the arterial, portal venous, and late phases and is particularly helpful for lesion characterization. The use of US for hemodynamic studies of the liver transit time may detect blood flow changes induced by micrometastases even before they become visible on imaging. In this field of functional imaging, further research is required to achieve conclusive results, which are not yet available.     

Hypoechoic focal liver lesions: characterization with contrast enhanced ultrasonography

PURPOSE: To evaluate the late sinusoidal phase of contrast enhancement with a 2nd-generation ultrasound contrast enhanced medium in the characterization of hypoechoic focal liver lesions. METHODS: We studied 88 hypoechoic liver lesions (diameter range, 1-18 cm; with 18 lesions 2 cm or less) found on conventional grayscale sonography (US) with contrast-enhanced ultrasonography (CEUS). Final diagnosis was made using contrast enhanced helical CT, contrast enhanced MR, angiography (DSA), and/or histopathic confirmation or clinical imaging follow-up. RESULTS: There were 37/88 benign lesions demonstrated: 17 cavernous hemangiomas, 3 capillary hemangiomas, 11 focal nodular hyperplasias (FNH), 3 focal areas of sparing in hepatic steatosis, 2 adenomas, and 1 intrahepatic necrotic area. Malignant lesions demonstrated included 51/88: 27 hepatocellular carcinomas (HCC) in cirrhosis, 11 metastatic carcinomas, 10 metastatic endocrine tumors, 2 cholangiocellular carcinomas (CCC) and 1 non-Hodgkin's lymphoma (NHL). CEUS characterized 30/37 (81%) benign lesions and 45/51 (88%) malignant lesions. On the basis of the results obtained during the sinusoidal contrast enhanced phase of CEUS, diagnosis of benignancy was possible in 35/37 (95%) of benign liver lesions and diagnosis of malignancy in 49/51 (96%) of malignant liver lesions. The enhancement pattern of 13 small (< or = 2 cm in diameter) hypervascular liver lesions (3 capillary hemangiomas, 2 FNHs, 4 HCCs, 4 metastatic endocrine tumors) was better demonstrated on CEUS than on helical CT. In these cases the hyper vascularization of the lesions shown on CEUS was not confirmed on CT. CONCLUSIONS: CEUS distinguished malignant from benign hypoechoic liver lesions with an accuracy of 95%.     

Contrast-enhanced sonography in the diagnosis of small hepatocellular carcinoma < or =2 cm

PURPOSE: To evaluate the usefulness of contrast-enhanced sonography (CEUS) in the diagnosis of small hepatocellular carcinoma (HCC) measuring < or =2 cm in diameter. METHODS: We identified 104 focal liver lesions measuring < or =2 cm in 104 consecutive patients who were enrolled for baseline sonography (BUS) and CEUS examination (49 HCCs, 55 non-HCCs). A real-time, contrast-specific mode of contrast pulse sequencing and a sulphur hexafluoride-filled microbubble contrast agent were used for CEUS. The diagnostic performances of BUS and CEUS in differentiating focal liver lesions (HCC or non-HCC) were analyzed and compared. RESULTS: On CEUS, 43 (87.8%) of the 49 HCC lesions were hyperenhanced, 5 (10.2%) were isoenhanced, and 1 (2%) was hypoenhanced during the arterial phase when compared with adjacent liver tissue. Thirty-nine (79.6%) HCCs exhibited washout from the portal phase to the late phase. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy before and after contrast agent administration were 28.6% (14/49) versus 79.6% (39/49) (p < 0.001), 94.5% (52/55) versus 92.7% (51/55) (p > 0.05), 82.4% (14/17) versus 90.7% (39/43) (p > 0.05), 59.8% (52/87) versus 90.7% (39/43) (p < 0.01), and 63.5% (66/104) versus 86.5% (90/104) (p < 0.001), respectively. No significant difference in diagnostic performance of CEUS was found between lesions measuring < or =1.5 cm and those 1.6-2 cm and between lesions located at a depth of < or =6 cm from the skin and those located deeper. CONCLUSIONS: CEUS significantly improved the diagnostic performance in characterization of small HCCs < or =2 cm compared with BUS.