Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading

Objective

To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions.

Materials and methods

99 patients (57 women and 42 men, age range 18–89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue^® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT.

Results

Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p < 0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p < 0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p < 0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ = 0.29–0.39) while it was good for CEUS (κ = 0.63–0.79).

Conclusions

CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.     

Clinical value of MRI liver-specific contrast agents: a tailored examination for a confident non-invasive diagnosis of focal liver lesions

Screening of the liver for hepatic lesion detection and characterization is usually performed with either ultrasound or CT. However, both techniques are suboptimal for liver lesion characterization and magnetic resonance (MR) imaging has emerged as the preferred radiological investigation. In addition to unenhanced MR imaging techniques, contrast-enhanced MR imaging can demonstrate tissue-specific physiological information, thereby facilitating liver lesion characterization. Currently, the classes of contrast agents available for MR imaging of the liver include non-tissue-specific extracellular gadolinium chelates and tissue-specific hepatobiliary or reticuloendothelial agents. In this review, we describe the MR features of the more common focal hepatic lesions, as well as appropriate imaging protocols. A special emphasis is placed on the clinical use of non-specific and liver-specific contrast agents for differentiation of focal liver lesions. This may aid in the accurate diagnostic workup of patients in order to avoid invasive procedures, such as biopsy, for lesion characterization. A diagnostic strategy that considers the clinical situation is also presented.     

Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts

The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost-benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the nonlinear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.     

Role of contrast enhanced ultrasound in characterization of focal liver lesions

Aim

The purpose of the study was to describe the enhancement patterns of focal liver lesions (FLLs) on contrast enhanced sonography (CEUS), assessing the potential of this technique for characterizing the lesions and to compare its diagnostic accuracy with conventional baseline sonography including color Doppler.

Materials and methods

Between August 2009 and July 2010, 50 patients with FLLs underwent gray scale sonography, color Doppler and CEUS. The enhancement patterns of these FLL’s were analyzed throughout the arterial phase, the portal venous phase and the extended portal venous phase (the late parenchymal phase). The final diagnosis was established on the basis of histopathologic examination or CT/MRI imaging.

Results

Out of these 50 FLLs, 33 were malignant (4 hepatocellular carcinoma and 29 metastasis) and 17 were benign (5 hemangioma, 5 abscess, 2 cyst and 1 each of FNH, focal fat sparing area, focal fatty infiltration, adenoma and benign/granulomatous lesion). The enhancement patterns after injecting microbubble contrast agent allowed characterization of FLLs. The malignant lesions showed intratumoral and/or peritumoral vascularity during the arterial phase and perfusion defect during the late parenchymal phase. Contrast enhanced sonography improved sensitivity in detecting malignancy (CEUS vs. baseline sonography, 100% vs. 81.8%).

Conclusion

CEUS improves detection and characterization of FLLs. It should be used as problem solving tool in cases where conventional gray scale and color Doppler sonography are non-diagnostic.     

Magnetic resonance imaging of the liver: New imaging strategies for evaluating focal liver lesions

The early detection of focal liver lesions, particularly those which are malignant, is of utmost importance. The resection of liver metastases of some malignancies (including colorectal cancer) has been shown to improve the survival of patients. Exact knowledge of the number, size, and regional distribution of liver metastases is essential to determine their resectability. Almost all focal liver lesions larger than 10 mm are demonstrated with current imaging techniques but the detection of smaller focal liver lesions is still relatively poor. One of the advantages of magnetic resonance imaging (MRI) of the liver is better soft tissue contrast (compared to other radiologic modalities), which allows better detection and characterization of the focal liver lesions in question. Developments in MRI hardware and software and the availability of novel MRI contrast agents have further improved the diagnostic yield of MRI in lesion detection and characterization. Although the primary modalities for liver imaging are ultrasound and computed tomography, recent studies have suggested that MRI is the most sensitive method for detecting small liver metastatic lesions, and MRI is now considered the pre-operative standard method for diagnosis. Two recent developments in MRI sequences for the upper abdomen comprise unenhanced diffusion-weighted imaging (DWI), and keyhole-based dynamic contrast-enhanced (DCE) MRI (4D THRIVE). DWI allows improved detection (b = 10 s/mm(2)) of small (< 10 mm) focal liver lesions in particular, and is useful as a road map sequence. Also, using higher b-values, the calculation of the apparent diffusion coefficient value, true diffusion coefficient, D, and the perfusion fraction, f, has been used for the characterization of focal liver lesions. DCE 4D THRIVE enables MRI of the liver with high temporal and spatial resolution and full liver coverage. 4D THRIVE improves evaluation of focal liver lesions, providing multiple arterial and venous phases, and allows the calculation of perfusion parameters using pharmacokinetic models. 4D THRIVE has potential benefits in terms of detection, characterization and staging of focal liver lesions and in monitoring therapy.     

The added diagnostic value of 64-row multidetector CT combined with contrast-enhanced US in the evaluation of hepatocellular nodule vascularity: implications in the diagnosis of malignancy in patients with liver cirrhosis

The aim of this study was to assess the added diagnostic value of contrast-enhanced US (CEUS) combined with 64-row multidetector CT (CT) in the assessment of hepatocellular nodule vascularity in patients with liver cirrhosis. One hundred and six cirrhotic patients (68 male, 38 female; mean age ± SD, 70 ± 7 years) with 121 biopsy-proven hepatocellular nodules (72 hepatocellular carcinomas, 10 dysplastic and 15 regenerative nodules, 12 hemangiomas, and 12 other benignancies) detected during US surveillance were prospectively recruited. Each nodule was scanned by CEUS during the arterial (10–40 s), portal venous (45–90 s), and delayed sinusoidal phase (from 100 s after microbubble injection to microbubble disappearance). Nodule vascularity at CEUS, CT, and combined CEUS/CT was evaluated side-by-side by two independent blinded readers who classified nodules as benign or malignant according to reference diagnostic criteria. The combined assessment of CEUS/CT provided higher sensitivity (97%, both readers) than did separate assessment of CEUS (88% reader 1; 87% reader 2) and CT (74% reader 1; 71% reader 2; P < 0.05), while no change in specificity was provided by combined analysis. The combined assessment of hepatocellular nodule vascularity at CT and CEUS improved sensitivity in the diagnosis of malignancy in patients with liver cirrhosis.     

肝脏局灶性病变MR动态增强扫描及临床意义

目的探讨肝脏局灶性病变ＭＲ动态增强扫描方法及临床意义。方法作者前瞻性研究了１３６例肝脏局灶性病变，包括肝细胞性肝癌、周围型肝内胆管细胞性肝癌、转移瘤及海绵状血管瘤。采用平静呼吸状态下梯度回波Ｋ空间中心部分采集技术、７个连续层面８个时相动态增强扫描。结果各例均动态增强扫描成功。动态扫描显示时间信号强度曲线在肝细胞性肝癌呈速升速降型；胆管细胞癌呈渐升型；转移瘤呈环形强化，缓慢升高型；海绵状血管瘤呈速升平台型。结论平静呼吸下Ｋ空间中心部分采集肝脏动态扫描，可以显示肝脏局灶病变的血供状态，而且不同病变具有不同的强化特征。     

肝脏局灶性病变MRI表现与病理学的相关性研究

肝脏局灶性病变的MRI信号强度受许多病理因素的影响。病变的组织学特征:细胞构成、血液供应、间质构成和肿瘤内的坏死或者出血等,都会使病变的T1及T2弛豫时间发生显著变化。细胞内的某些内容物:糖原、脂肪、黑色素、铁和铜,在决定MRI信号表现方面起着重要的作用。MRI与病理学之间联系的研究对于诊断局灶性病变非常有帮助。     

Ultrasound contrast agents: clinical applications

Ultrasound contrast agents (USCA) for intravenous injections are usually gas-filled microbubbles with a mean diameter less than that of a red blood corpuscle. There are only a few products on the market at the time of this writing, but several companies have various agents under development. This paper covers both established USCA on the market, and some new agents under clinical evaluation. The potential of improving ultrasound imaging using USCA depends on several factors. These factors include the pharmacokinetic and pharmacodynamic properties of the products, which determine the effects they have on various ultrasound imaging techniques. Furthermore, the proper clinical application of the agents requires a combination of technical and medical knowledge by the examiner, dedicated equipment, a disease that can be diagnosed or characterised by ultrasound and USCA, and a cooperative patient. Taking into account these factors, USCA can be used for improving the detection, characterisation and follow-up of diseases of several vascular beds and parenchymal organs from head to foot.     

Clinical utility of contrast-enhanced three-dimensional ultrasound imaging with Sonazoid: findings on hepatocellular carcinoma lesions

Objectives

We investigated clinical utility of contrast-enhanced three-dimensional ultrasound (CE 3D US) imaging with contrast medium Sonazoid for demonstrating characteristic enhancement of hepatocellular carcinoma (HCC).

Methods

Among 115 focal liver tumors undergoing CE 3D US imaging, 70 HCCs confirmed with contrast-enhanced multi-detector computed tomography, contrast-enhanced magnetic resonance imaging or histopathologic examination were retrospectively analyzed. CE 3D US imaging was performed using Autosweep 3D scan functionality in the early, middle and late phase, after bolus injection of 0.2 ml Sonazoid. The CE 3D tomographic images reconstructed in parallel slices and sonographic angiogram images were independently reviewed by two reviewers. Kappa values were used to assess inter-reviewers’ agreement.

Results

TUI images showed most of HCCs were detected with intratumoral vessels and early tumor enhancement in the early phase, expressed homogenous or heterogeneous tumor enhancement in the middle phase, and became hypoechoic or isoechoic in the late phase. The kappa values in the early, middle and late phase for inter-reviewer agreements regarding the characteristic enhancement of tumors were 0.817, 0.774, and 0.785. In addition, TUI images demonstrated satellite foci and tortuous tumor vessels in three orthogonal planes. Sonographic angiogram reconstructed by different rendering modes showed the vessels and tumor stain in spatial view. The spatial configuration of anatomic structures was revealed on basis of both TUI and sonographic angiogram images.

Conclusion

CE 3D US imaging, with spatial visualization, is clinically useful to exhibit the characteristic enhancement of HCC tumors objectively.     

Benign focal liver lesions: spectrum of findings on SonoVue-enhanced pulse-inversion ultrasonography

The prevalence of benign focal liver lesions (BFLL) is high both in the general population and in patients with known malignancies. The gray-scale ultrasound (US) technique is usually the first-line imaging modality used in the radiological workup of such lesions, but unfortunately it lacks specificity. Furthermore, Doppler examination may often be unsatisfactory owing to motion artefacts, or when small or deeply located lesions are evaluated. Recently, microbubble-based contrast agents used in combination with gray-scale US techniques, which are very sensitive to nonlinear behavior of microbubbles, have led to a better depiction of both microvasculature and macrovasculature of focal hepatic masses, thus improving the reliability of using US in the assessment of liver tumors. This review illustrates the spectrum of enhancement patterns of BFLL on contrast-enhanced ultrasonography with SonoVue, a second-generation microbubble-based contrast agent.This paper is based on a work accepted for presentation as a scientific paper at the Scientific Assembly and Annual Meeting of the ECR 2004.     

Detection and characterization of benign focal liver lesions with multislice CT

MDCT is a rapidly evolving technique that significantly improves CT imaging for several indications including depiction of focal benign lesions. Imaging mainly profits from improved longitudinal spatial resolution allowing high-quality non-axial reformations and 3D reconstructions and CT angiography as well as rapid accurate multiphase imaging with short breath-holding periods. This review provides an overview of the current status of MDCT with respect to liver imaging and the implications for characterizing benign focal liver lesions. MDCT currently allows the acquisition of thin slices in daily routine diagnostics providing an improved detection rate of small liver lesions. Whereas large benign focal liver lesions exhibit typical patterns of morphology, attenuation and perfusion, which also may be assessed with single-slice scanners, small lesions remain challenging even with MDCT, since the specific criteria for confident diagnosis become more ambiguous. Here, MR imaging provides more detailed information about tissue components and the availability of liver-specific contrast agents, adding further impact to this technique. With respect to dose considerations, the number of necessary multiphase scans as well as the application of very thin collimation should be strictly checked for each patient undergoing MDCT based on the individual clinical situation and question.     

ADC值在鉴别肝脏良恶性局灶性病变的应用价值

目的 评价ADC值在鉴别肝脏良恶性局灶性病变(focal liver lesion,FLL)的诊断价值.方法 采用signa 3.0T MR对306例共391个FLL进行屏气DWI成像(b=800s/mm2),包括肝囊肿78灶,成熟肝脓肿23灶,肝血管瘤39灶,FNH\肝腺瘤17灶,原发性肝癌121灶,胆管细胞癌45灶,肝转移癌68灶.DWI图像经GE公司AW4.2工件站后处理得到ADC图,测量以上各类病灶的ADC值,统计分析良恶性性FLL的ADC值及其差异.结果 良恶性FLL的平均ADC值(×10-3 mm2/s)分别为2.63±0.35、1.18士0.41,差异有统计学意义(P=0.007).以ADC≤1.64×10-3 mm2/s诊断恶性FLL的敏感性、特异性和准确率分别为:87％、81％、84％.结论 恶性FLL的ADC值明显低于良性,以ADC值能明显提高对肝脏局灶性病变良恶性的鉴别诊断能力.     

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence

Aim: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. Materials and methods: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. Results: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P<0.01) while did not differ from CT (89%, 89%, 0.945, respectively; P>0.05). Conclusion: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.     

Multifocal inflammatory pseudotumor of the liver: dynamic gadolinium-enhanced, ferumoxides-enhanced, and mangafodipir trisodium-enhanced MR imaging findings

The MRI characteristics of a multifocal inflammatory pseudotumor of the liver are described. Emphasis is placed on the appearances following intravenous administration of both non-specific and liver-specific MR contrast agents. On post-gadolinium gradient-echo (GE) images an early, intense, and peripheral enhancement was followed by a homogeneous, complete, and persistent enhancement. Lesions showed no uptake following administration of ferumoxides particles nor mangafodipir trisodium, respectively. During follow-up, a peripheral hyperintense rim appeared on precontrast T1-weighted images, a feature not previously described.     

Microbubble ultrasound contrast agents: an update

Microbubble contrast agents for ultrasound (US) have gained increasing interest in recent years, and contrast-enhanced US (CEUS) is a rapidly evolving field with applications now extending far beyond the initial improvements achieved in Doppler US. This has been achieved as a result of the safe profile and the increased stability of microbubbles persisting in the bloodstream for several minutes, and also by the availability of specialized contrast-specific US techniques, which allow a definite improvement in the contrast resolution and suppression of signal from stationary tissues. CEUS with low transmit power allows real-time scanning with the possibility of prolonged organ insonation. Several reports have described the effectiveness of microbubble contrast agents in many clinical applications and particularly in the liver, spleen, and kidneys. CEUS allows the assessment of the macrovasculature and microvasculature in different parenchymas, the identification and characterization of hepatic and splenic lesions, the depiction of septal enhancement in cystic renal masses, and the quantification of organ perfusion by the quantitative analysis of the echo-signal intensity. Other fields of application include the assessment of abdominal organs after traumas and the assessment of vesico-ureteral reflux in children. Finally, tumor-targeted microbubbles make possible the depiction of specific biologic processes.     

Impact of European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines on the use of contrast agents in liver ultrasound

The introduction of microbubble contrast agents and the development of contrast-specific techniques have opened new prospects in liver ultrasound. Over the past few years several reports have shown that contrast ultrasound can substantially improve detection and characterization of focal liver lesions with respect to baseline studies. The advent of second-generation agents and low mechanical index real-time scanning techniques has been instrumental in improving the easiness and the reproducibility of the examination. With the publication of the guidelines for the use of contrast agents in liver ultrasound by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), contrast ultrasound enters into clinical practice. The guidelines define the indications and recommendations for the use of contrast ultrasound in focal liver lesion detection, characterization, and follow-up after tumor ablation procedures. We discuss the impact of EFSUMB guidelines on diagnostic protocols currently adopted in liver imaging.     

常规SE序列和动态增强MRI诊断肝局灶性病变的比较

目的比较常规SE序列与动态Gd-U．----x增强扫描对肝局灶病变的诊断价值。方法对34例肝局灶病变做了常规SE平扫和动态Gd-U．---A增强及延迟万WI增强扫描；就各序列对肝局灶病变的检出率、病变的信噪比（C／N）值和图像质展进行定员和定性分析。结果36例共142个病灶，动态Gd-lyl？l？A检出率（138／142，958％）明st高于IFZWI和延迟TW［增强（128／14，叨％；119／142，838％）（P＜005）：动态Gd-IJ：1713A增强的C／N值高于TZWI和TIWI延迟增强（P＜0．05）；动态增强的伪影较L们少（P＜0．01），而病灶清晰度各序列之间无明显差别（P＞0．历）。结论动态u-ly：1717A增强扫描在病灶检出率、图像质显反C／N值方面均优于IWI，对肝局灶病变的诊断是一种有价值的方法，     

Characterization of focal liver lesions by ADC measurements using a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging technique

The aim of this study was to determine apparent diffusion coefficients (ADCs) of focal liver lesions on the basis of a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging sequence (DW-SS-EPI) and to evaluate whether ADC measurements can be used to characterize lesions. One hundred and two patients with focal liver lesions [11 hepatocellular carcinomas (HCC), 82 metastases, 4 focal nodular hyperplasias (FNH), 56 hemangiomas and 51 cysts; mean size, 16.6 mm; range 5–92 mm] were examined on a 1.5-T system using respiratory triggered DW-SS-EPI (b-values: 50, 300, 600 s/mm²). Results were correlated with histopathologic data and follow-up imaging. The ADCs of different lesion types were compared, and lesion discrimination using optimal thresholds for ADCs was evaluated. Mean ADCs (×10⁻³mm²/s) were 1.24 and 1.04 for normal and cirrhotic liver parenchyma and 1.05, 1.22, 1.40, 1.92 and 3.02 for HCCs, metastases, FNHs, hemangiomas and cysts, respectively. Mean ADCs differed significantly for all lesion types except for comparison of metastases with HCCs and FNHs. Overall, 88% of lesions were correctly classified as benign or malignant using a threshold value of 1.63 × 10⁻³mm²/s. Measurements of the ADCs of focal liver lesions on the basis of a respiratory triggered DW-SS-EPI sequence may constitute a useful supplementary method for lesion characterization.