Characterization Of Liver Tumors Research Articles

Liver Tumor Characterization – Review of the Literature

Multicenter trials to assess contrast-enhanced ultrasound (CEUS) for the imaging of focal liver lesions (FLLs) have included more than 1000 patients. This article reviews the published literature pertaining to these trials to determine the role of CEUS in the characterization of FLL.

Liver Tumor Characterization – Comments and Illustrations Regarding Guidelines

Contrast-enhanced ultrasound (CEUS) is a well established diagnostic imaging technique for a variety of indications and applications. One of the most important applications is in the liver where it is frequently a first-line technique for the detection and diagnosis (characterization) of focal liver lesions (FLLs). In this setting the accurate differentiation of benign lesions from malignant lesions is critical to ensure that the patient undergoes the appropriate therapeutic option. In this article the role of CEUS in the characterization of FLLs is described on the basis of recently published guidelines, in particular in terms of the enhancement patterns of the most common FLLs, e. g. hemangioma, focal nodular hyperplasia, hepatocellular adenoma and their differentiation from malignant lesions.

Diffusion-weighted MR Imaging for the Regional Characterization of Liver Tumors

To determine if diffusion-weighted (DW) magnetic resonance (MR) imaging with measurements of the apparent diffusion coefficient (ADC), pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction can be used to differentiate between viable tumor and fibrous and necrotic regions within malignant liver tumors. The prospective study was approved by the institutional review board, and informed consent was obtained from all patients. Forty-eight patients with 51 malignant tumors were assessed. MR images of the liver were obtained by using DW imaging with 11 b factors (0-500 sec/mm(2)) and gadolinium-enhanced three-dimensional gradient-echo T1-weighted imaging. Tumors were segmented into viable tumor and fibrous and necrotic regions according to the enhancement pattern after injection of a nonspecific gadolinium chelate and, in surgically removed lesions, results of histopathologic correlation. The ADC, pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction were calculated, and values were compared between viable tumor and fibrous and necrotic regions with the Kruskal-Wallis test followed by the Dunn multiple comparison test. The pure diffusion coefficient differed significantly between regions of viable tumor tissue and fibrosis (1.16 × 10(-3) mm(2)/sec ± 0.29 and 1.48 × 10(-3) mm(2)/sec ± 0.31, respectively; P = .016) and between regions of viable tumor tissue and necrosis (1.70 × 10(-3) mm(2)/sec ± 0.49, P = .002). There was a significantly lower perfusion fraction in necrotic regions (14% ± 6) than in viable tumor regions (21% ± 8, P = .005), but the perfusion fraction of the fibrous regions (21% ± 7) did not differ significantly from that of the other two regions. ADCs and perfusion-related diffusion coefficients did not differ significantly among the three regions. Results of this study show that viable tumor regions in malignant liver tumors can be differentiated from fibrous and necrotic regions with use of the pure diffusion coefficient but not with the other diffusion parameters.

MR elastography of liver tumours: value of viscoelastic properties for tumour characterisation

To assess the value of the viscoelastic parameters in the characterisation of liver tumours at MR elastography. Ninety-four patients with liver tumours >1cm prospectively underwent MR elastography using 50-Hz mechanical waves and a full three-directional motion-sensitive sequence. The model-free viscoelastic parameters (the complex shear modulus and its real and imaginary parts, i.e. the storage and loss moduli) were calculated in 72 lesions after exclusion of cystic, treated or histopathologically undetermined tumours. We observed higher absolute shear modulus and loss modulus in malignant versus benign tumours (3.38 ± 0.26 versus 2.41 ± 0.15 kPa, P < 0.01 and 2.25 ± 0.26 versus 1.05 ± 0.13 kPa, P < 0.001, respectively). Moreover, the loss modulus of hepatocellular carcinomas was significantly higher than in benign hepatocellular tumours. The storage modulus did not differ significantly between malignant and benign tumours. The area under the receiver-operating characteristic curve of loss modulus was significantly larger than that of the absolute shear modulus and storage modulus when comparing malignant and benign lesions. The increased loss modulus is a better discriminator between benign and malignant tumours than the increased storage modulus or absolute value of the shear modulus. • Magnetic Resonance elastography is a new method of assessing the liver. • Increased loss modulus is an indicator of malignancy in hepatic tumours. • Loss modulus is a better discriminator than absolute shear modulus values. • The viscoelastic properties of lesions offer promise for characterising liver tumours.

Hepatoblastoma imaging with gadoxetate disodium-enhanced MRI—typical, atypical, pre- and post-treatment evaluation

Gadoxetate disodium (Gd-EOB-DTPA) is a hepatobiliary MRI contrast agent widely used in adults for characterization of liver tumors and increasingly used in children. Hepatoblastoma is the most common primary hepatic malignancy of childhood. In this review, we describe our experience with this agent both before and after initiating therapy in children with hepatoblastoma.

Comparison of Two-Dimensional Versus Three-Dimensional Ultrasonography in the Detection and Characterization of Liver Tumors

Comparison of Two-Dimensional Versus Three-Dimensional Ultrasonography in the Detection and Characterization of Liver Tumors

Kontrastmittelverstärkte Sonographie

Due to the imaging of dynamic perfusion, hepatocellular carcinoma can be detected with a sensitivity of >90% using contrast-enhanced sonography. The characterization of liver tumors with contrast-enhanced sonography is comparable to the diagnostic accuracy of contrast-enhanced computed tomography. The dynamic detection of microvascularization with contrast-enhanced sonography allows the differentiation between vascularized tumors and non-vascularized necrotic lesions before, during and after transarterial chemoembolization or percutaneous radiofrequency ablation. Image fusion with volume navigation can be useful in the followup control.

Vascular Profile Characterization of Liver Tumors by Magnetic Resonance Imaging Using Hemodynamic Response Imaging in Mice

Recently, we have demonstrated the feasibility of using hemodynamic response imaging (HRI), a functional magnetic resonance imaging (MRI) method combined with hypercapnia and hyperoxia, for monitoring vascular changes during liver pathologies without the need of contrast material. In this study, we evaluated HRI ability to assess changes in liver tumor vasculature during tumor establishment, progression, and antiangiogenic therapy. Colorectal adenocarcinoma cells were injected intrasplenically to model colorectal liver metastasis (CRLM) and the Mdr2 knockout mice were used to model primary hepatic tumors. Hepatic perfusion parameters were evaluated using the HRI protocol and were compared with contrast-enhanced (CE) MRI. The hypovascularity and the increased arterial blood supply in well-defined CRLM were demonstrated by HRI. In CRLM-bearing mice, the entire liver perfusion was attenuated as the HRI maps were significantly reduced by 35%. This study demonstrates that the HRI method showed enhanced sensitivity for small CRLM (1-2 mm) detection compared with CE-MRI (82% versus 38%, respectively). In addition, HRI could demonstrate the vasculature alteration during CRLM progression (arborized vessels), which was further confirmed by histology. Moreover, HRI revealed the vascular changes induced by rapamycin treatment. Finally, HRI facilitates primary hepatic tumor characterization with good correlation to the pathologic differentiation. The HRI method is highly sensitive to subtle hemodynamic changes induced by CRLM and, hence, can function as an imaging tool for understanding the hemodynamic changes occurring during CRLM establishment, progression, and antiangiogenic treatment. In addition, this method facilitated the differentiation between different types of hepatic lesions based on their vascular profile noninvasively.

Unclear Focal Liver Lesions in Contrast-Enhanced Ultrasonography – Lessons to be Learned from the DEGUM Multicenter Study for the Characterization of Liver Tumors

To discuss the difficulties of contrast-enhanced ultrasound (CEUS) in a large multi-center trial. CEUS was performed on 1349 liver lesions with an unclear diagnosis after native ultrasound using a standardized protocol (phase inversion; low MI < 0.4; Sonovue Bolus 1.2 - 4.8 ml). The early arterial, arterial, portal venous and late phase > 2 min. were documented. The diagnosis based on CEUS results was compared to the final diagnosis (histology: n = 1006; MRI: n = 269; CT: n = 269 - multiple examinations possible). Of the 1349 enclosed liver lesions, 20 could not be definitively diagnosed even using all diagnostic steps including histology (the others were proven to be benign n = 573 or malignant n = 756). Of the 1349 unclear liver lesions, 1257 could be differentiated with an accuracy of 90.3% using CEUS. The sensitivity, specificity, and positive and negative predictive value for malignant liver lesions was 95.8%, 83.1%, 88.2% and 93.7% respectively. 92 liver lesions (6.8%) could not be definitively diagnosed using CEUS. Most of them were benign (n = 67) on final diagnosis. The CEUS diagnosis was wrong for 39 lesions. However, only 8 lesions classified as benign by CEUS turned out to be malignant. In 3 cases HCC proven by histology was incorrectly diagnosed by CEUS as adenoma and 2 lesions incorrectly diagnosed by CEUS as FNH turned out to be an HCC and a metastasis. Two lesions diagnosed by CEUS as hemangiomas turned out to be an HCC and a metastasis. One lesion classified as benign by CEUS was ultimately diagnosed as a lymphoma. Even in this multi-center trial, CEUS proved to be an excellent method for clarifying liver lesions remaining unclear after native ultrasound. The CEUS diagnosis of benign was only incorrect in a few cases.

Effect of Observer Experience in the Differentiation Between Benign and Malignant Liver Tumors After Ultrasound Contrast Agent Injection

The purpose of this study was to assess the impact of the observer level of experience on the diagnostic performance of contrast-enhanced ultrasound imaging (CEUS) for differentiation between benign and malignant liver tumors. From a computerized search, we retrospectively identified 286 biopsy-proven liver tumors (105 hepatocellular carcinomas, 48 metastases, 7 intra-hepatic cholangiocarcinomas, 33 liver hemangiomas, and 93 nonhemangiomatous benign lesions) in 235 patients (140 male and 95 female; mean age +/- SD, 56 +/- 11 years) who underwent CEUS after sulfur hexafluoride-filled microbubble injection. The digital cine clips recorded during the arterial (10-35 seconds from injection), portal (50-120 seconds), and late (130-300 seconds) phases were analyzed by 6 independent observers without experience (group 1, observers 1-3) or with 2 to 10 years of experience in CEUS (group 2, observers 4-6). Specific training in the diagnostic and interpretative criteria was provided to the inexperienced observers. Each observer used a 5-point scale to grade diagnostic confidence: 1, definitely benign; 2, probably benign; 3, indeterminate; 4, probably malignant; or 5, definitely malignant on the basis of the enhancement pattern during the arterial phase and enhancement degree during the portal and late phases compared with the liver (hypoenhancement indicating malignant and isoenhancement to hyperenhancement indicating benign). The analysis of observer diagnostic confidence revealed higher intragroup (kappa = 0.63-0.83) than intergroup (kappa = 0.47-0.63) observer agreement. The experienced observers showed higher diagnostic performance in malignancy diagnosis than did inexperienced observers (overall accuracy: group 1, 63.3%-72.8%; group 2, 75.9%-93.1%; P < .05, chi(2) test). The diagnostic performance of CEUS in liver tumor characterization was dependant on the observer's level of experience.

Contrast-enhanced ultrasound in the detection and characterization of liver tumors.

Contrast-enhanced ultrasound (CEUS) has unique advantages over contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) in the characterization of hepatic tumors. These include the capability of real-time dynamic imaging depicting the enhancement pattern of tumors regardless of its rapidity, purely intravascular properties of the microbubble contrast agents more consistently demonstrating washout of malignancy, and capability of repetitive observation of tumor vascularity with multiple injections of microbubbles with an excellent safety profile and no nephrotoxicity. For an indeterminate mass detected on an ultrasound scan, an immediate benign diagnosis reduces the necessity of costly further imaging as well as patients’ anxiety and an immediate malignant diagnosis prompts the proper work-up and management. CEUS is often served as a problem-solving tool for indeterminate lesions on prior CT or MRI scans, obviating further invasive steps. CEUS offers excellent visualization of peripheral nodular enhancement in even flash-filling or very slow-filling hemangiomas. Careful observation of early arterial filling pattern is helpful in the differentiation of focal nodular hyperplasia versus adenoma. Hepatocellular carcinoma is typically characterized by arterial hypervascularity and often late, partial washout. Metastasis shows brief arterial hypervascularity and complete rapid washout, which can improve its detection during a portal phase survey. The washout phenomenon of malignant tumors in general is useful to differentiate them from benign lesions.

Comments and Illustrations Regarding the Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) – Update 2008

The recently published EFSUMB guidelines and recommendations provide general advice for the use of ultrasound contrast agents to improve the management of patients. They are the subject of this pictorial essay, comments and analysis of the literature. CEUS has become the most important imaging method for focal liver diseases. Its uses are discussed in detail, especially the characterization of liver tumors and the monitoring of local treatment. The recommendations also deal with the uses of ultrasound contrast agents for the evaluation of the microvasculature and macrovasculature of the kidneys, including the characterization of focal renal lesions, the detection of lesions and the monitoring of local treatment. CEUS and contrast-enhanced endoscopic ultrasound can be used to characterize lesions. Ductal adenocarcinoma as the most common tumor of the pancreas is typically hypoenhanced compared to the adjacent pancreatic tissue in all phases. Neuroendocrine tumors and serous microcystic adenoma of the pancreas are characterized by hypervascularization appearing typically hyperenhanced during CEUS. This is of importance for a differential diagnosis. Vesicoureteric reflux and blunt abdominal trauma are also mentioned. Other parts or chapters of the guidelines are described in a separate paper of this supplement.

Improved characterisation of solitary solid pancreatic tumours using contrast enhanced transabdominal ultrasound

Contrast enhanced ultrasound (CEUS) is a new imaging method for detection and characterisation of liver tumours. The role of CEUS in pancreatic disease is less obvious. We prospectively evaluated CEUS for characterization of undetermined solid pancreatic lesions (gold standard histology). A total of 112 solitary undetermined pancreatic masses (70 ductal adenocarcinoma and 42 neoplastic nodules of other origin) were prospectively examined in patients without metastatic disease using transabdominal ultrasound. Tumour enhancing features were analyzed in comparison to the surrounding pancreatic parenchyma in patients with adequate visualisation. The sign of iso-hypervascularity as a sign of non-ductal adenocarcinoma showed a sensitivity of 100%, specifity of 90% and accuracy of 93.8%. The sign of hypovascularity as a sign of ductal adenocarcinoma showed a sensitivity of 90%, specifity of 100% and an accuracy of 93.8%. CEUS allows differential diagnosis of ductal adenocarcinoma and non-ductal adenocarcinoma (mainly neuroendocrine tumours and (microcystic) serous pancreatic adenoma) in the most of cases.

Improved differentiation of pancreatic tumours using contrast enhanced transabdominal ultrasound

Aim: Contrast enhanced ultrasound (CEUS) is a new imaging method for detection and characterisation of liver tumours. The role of CEUS in pancreatic disease is less obvious. We prospectively evaluated CEUS for characterization of histologically proven solid pancreatic tumours.

Current status of body MR imaging: fast MR imaging and diffusion-weighted imaging

The recent technical advances in fast MR imaging have greatly enhanced the clinical value of MR imaging of the body. Advances in T(1)-weighted images have enabled the acquisition of dynamic contrast-enhanced MR imaging, which is currently central to hepatic MR imaging for detection and characterization of liver tumors and is also useful for the evaluation of myometrial invasion in uterine cor-pus cancer. Advances in rapid T(2)-weighted MR imaging with single-shot fast spin-echo images have enabled MR cholangiopancreatography and MR urography. Application of respiratory triggering can also provide T(2)-weighted images of high quality. Cine MR imaging utilizing ultrafast MR sequences enables the assessment of the respiratory motion of the lung for evaluating thoracic wall invasion by tumors. Diffusion-weighted images can provide excellent tissue contrast based on molecular diffusion and have the potential to demonstrate malignant tumors. Quantitative measurement of apparent diffusion coefficient values may also be valuable in distinguishing malignancies from benign lesions.

Comparison of Visual and Quantitative Analysis for Characterization of Insonated Liver Tumors After Microbubble Contrast Injection

The objective of our study was to compare diagnostic performance of visual and quantitative analysis for the characterization of liver tumors insonated at low transmit power after microbubble contrast agent injection. This series comprised 166 liver tumors (1-5 cm in diameter) in 166 patients (99 men, 67 women; mean age +/- SD, 58 +/- 11 years) scanned at low transmit power (mechanical index: 0.1-0.14) after sulfur hexafluoride-filled microbubble injection. Digital cine clips recorded at the arterial phase (10-40 sec after contrast injection) and late phase (100-300 sec) were analyzed to characterize liver tumors as benign or malignant. Visual analysis was performed by three independent blinded reviewers who evaluated enhancement patterns at the arterial phase and subjective tumor conspicuity at the late phase. Quantitative analysis of videotape intensity (VI: gray-scale levels, 0-255) was performed to calculate objective tumor conspicuity at the late phase: (VI(tumor) - VI(liver)) / VI(liver). Characteristic enhancement patterns were observed in malignant tumors (peripheral rimlike) and benign tumors (peripheral nodular or central and spoke-wheel-shaped). Malignant (n = 95) versus benign (n = 71) tumors differed for subjective (median value: -1 vs 1, respectively) and objective conspicuity at the late phase (-0.6 vs 0.15, respectively; p = 0.001, Mann-Whitney U test) due to persistent microbubble uptake in benign tumors. Diagnostic performance of visual (odds ratio: reviewer 1 = 4.28, reviewer 2 = 10.18, reviewer 3 = 9.56) and quantitative (odds ratio: 89.33) analyses differed significantly in the characterization of liver tumors (p = 0.01, chi-square test). Quantitative analysis revealed higher diagnostic performance than visual analysis to characterize liver tumors insonated at low transmit power after microbubble contrast agent injection.

1239: Characterization of liver tumors with contrast enhanced multiphase dynamic US

1239: Characterization of liver tumors with contrast enhanced multiphase dynamic US

Contrast-enhanced multiphase dynamic ultrasonography for the characterization of liver tumors.

The purpose of the study was to introduce our protocol for contrast-enhanced multiphase dynamic ultrasonography (US) and examine the effectiveness of this method for characterizing liver tumors. The subjects were 142 patients with liver tumors. The final diagnoses were 58 hepatocellular carcinomas (HCCs), 4 cholangiocellular carcinomas (CCCs), 14 metastases, 29 hemangiomas, 6 cases of focal nodular hyperplasia (FNH), and 31 other benign lesions. The contrast agent used was Levovist. A wide-band pulse inversion harmonic imaging mode was employed. Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu. Early arterial-phase images were observed at the short interval, and an equilibrium-phase image was observed at the longest interval. After a series of vascular images, a postvascular liver parenchymal image was obtained. Based on previously published criteria, the most compatible diagnosis was noted. The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospective study. The overall accuracy of all 142 cases was 93.7%. The sensitivity, specificity, and positive predictive value were, respectively, 100%, 92.9%, and 90.6% for HCC; 88.9%, 97.6%, and 84.2% for metastasis or CCC; 89.7%, 100%, and 100% for hemangioma; and 83.3%, 100%, and 100% for FNH. Contrast-enhanced multiphase dynamic US is a highly accurate, safe diagnostic tool for characterizing liver tumors.

Characterisation of focal liver lesions with contrast enhanced ultrasonography

Ultrasound contrast agents (USCA) have improved the detection rate of liver tumours in recent years. Conventional ultrasound has been reported to be relatively unreliable in the characterisation of liver tumours. SonoVue ® (Bracco Imaging Spa) has been shown to be particularly advantageous in the differentiation of benign and malignant liver tumours and, therefore, possibly represents a new cost-effective competitive alternative to other liver imaging modalities (e.g. computed tomography and magnetic resonance imaging), thus allowing these important technologies to be available for other indications (e.g. brain, thorax). More detailed and specific liver tumour characterisation is possible in about 80% of liver tumours due to typical vascularity and perfusion patterns. The role of USCA for better characterisation, which is possible through the analysis of flow characteristics in real time, places a particular emphasis on agent use. Contrast enhanced real-time imaging techniques with SonoVue ® allow real-time analysis of tumour perfusion in patients with liver lesions. Liver tumours known to be hyperperfused in the arterial phase (e.g. focal nodular hyperplasia, hepatocellular adenoma and carcinoma, and hyperperfused metastases) can be better detected and characterised. Hypoperfused tumours (e.g. liver metastases of the gastrointestinal tract) can be recognised in the portal venous phase as less perfused “black spots.” In this article we discuss liver tumour characterisation by contrast enhanced ultrasonography.

Evaluation of the Time Window for Resovist-Enhanced T2-Weighted MRI of the Liver

Superparamagnetic iron oxides (SPIO) are phagocytized in the reticuloendothelial system (RES) of the liver and spleen. Most liver tumors are devoid of RES cells and do not show uptake of SPIO. Therefore, SPIO increase tumor-liver contrast and subsequently the detection and the characterization of liver tumors (1 6). Contrastenhanced MRI may be performed as early as 10 min following administration of the new SPIO SHU 555 A with a blood half-live 3.9 5.8 min (7, 8). With the upcoming clinical approval of this new SPIO the question arises how long the time window for a stable contrast-enhanced T2-weighted MRI of the liver will be. Thus, the purpose of this study was to estimate the time window for contrast-enhanced MRI of the liver with SHU 555 A by measuring signal intensity within the liver and liver tumors on T2-weighted MRI over a period up to 2 weeks following contrast administration.