Microvascular flow imaging (MVFI) is an advanced Doppler ultrasound technique designed to detect slow-velocity blood flow in small-caliber microvessels. This technique is capable of realtime, highly detailed visualization of tumor vessels without using a contrast agent. MVFI has been recently applied for the characterization of focal liver lesions and has revealed typical vascularity distributions in multiple types thereof. Focal nodular hyperplasia (FNH) constitutes an important differential diagnosis of malignant liver tumors. In this essay, we provide iconographic documentation of the MVFI appearance of FNH and other common solid liver lesions. Identifying the typical patterns of vascularity, including the spoke-wheel pattern with MVFI, can expedite the diagnosis, spare patients from unnecessary procedures, and save costs.

Power Doppler (PD) is a commonly used technique for flow detection and vessel visualization in radiology clinics. Despite its broad set of applications, PD suffers from multiple noise sources and artifacts, such as thermal noise, clutter, and flash artifacts. In addition, a tradeoff exists between acquisition time and Doppler image quality. These limit the ability of clinical PD imaging in deep-lying and small-vessel detection and visualization, particularly among patients with high body mass indices (BMIs). To improve the Doppler vessel detection, we have previously proposed coherent flow PD (CFPD) imaging and demonstrated its performance on porcine vasculature. In this article, we report on a pilot clinical study of CFPD imaging on healthy human volunteers and patients with high BMI to assess the clinical feasibility of the technique in liver imaging. In this study, we built a real-time CFPD imaging system using a graphical processing unit (GPU)-based software beamformer and a CFPD processing module. Using the real-time CFPD imaging system, the liver vasculature of 15 healthy volunteers with normal BMI below 25 and 15 patients with BMI greater than 25 was imaged. Both PD and CFPD image streams were produced simultaneously. The generalized contrast-to-noise ratio (gCNR) of the PD and CFPD images was measured to provide the quantitative evaluation of image quality and vessel detectability. Comparison of PD and CFPD image shows that gCNR is improved by 35% in healthy volunteers and 28% in high BMI patients with CFPD compared to PD. Example images are provided to show that the improvement in the Doppler image gCNR leads to greater detection of small vessels in the liver. In addition, we show that CFPD can suppress in vivo reverberation clutter in clinical imaging.

Imaging manifestations of hepatic lymphoma, both primary (PHL) and secondary (SHL), are extremely variable and non-specific, but some features are useful diagnostic clues in an appropriate clinical setting. Through a PubMed search, we found several published reviews focused on PHL and SHL diagnosis. However, to the best of our knowledge, few of them encompass a comprehensive analysis of all the diagnostic tools and relative radiological findings. The aim of this review is to provide a description of the radiological features of both PHL and SHL, by critically analyzing the available literature.

An extensive review of published literature along with a description of personal case series of both PHL and SHL has been conducted.

SHL can be easily diagnosed with imaging techniques, as it is usually associated with node disease. On the contrary the diagnosis can be a challenge in PHL, often mimicking HCC or liver metastasis of adenocarcinoma. In this context, multiparametric MRI plays a fundamental role in the differential diagnosis. Both for PHL and SHL, liver involvement presents as solitary or multiple lesions or as diffuse infiltrative disease.

PHL and SHL may be correctly characterized using different radiological techniques. Both CT and MRI have showed a good correlation with histology, as they permit to distinguish between lymphomatous tissue, and necrotic and fibrotic areas.

The purpose of this article is to discuss the use of contrast-enhanced ultra-sound (CEUS) in focal liver lesions.

Focal liver lesions are usually detected incidentally during abdominal ultrasound. The injection of microbubble ultrasound contrast agents improves the characterization of focal liver lesions that are indeterminate on conventional ultrasound. The use of CEUS is recommended in official guidelines and suggested as a second diagnostic step after ultrasound detection of indeterminate focal liver lesions to immediately establish the diagnosis, especially for benign liver lesions, such as hemangiomas, avoiding further and more expensive examinations.

The purpose of this study was to introduce a new high-definition flow (HDF) Doppler technique and to compare its performance with those of color Doppler ultrasonography (CDU) and power Doppler ultrasonography (PDU) for assessment of hepatic vasculature in native and transplanted livers.

High-definition flow was invented as a high-resolution bidirectional PDU technique. We obtained CDU, PDU, and HDF images of the hepatic artery (HA), portal vein (PV), and hepatic vein from 60 patients. They were divided into 2 groups: a liver transplantation group (group 1, n = 10) and a native liver group (group 2, n = 50). Two radiologists independently reviewed the cine images and graded them using a 4-point scale in terms of the clarity of the vessel margin and degree of depiction of the HA, flow filling, and flash artifacts. The degree of differentiation between the HA and PV was also evaluated. Flow directionality was recorded, and interobserver agreement was finally analyzed.

Moderate to almost perfect agreement was achieved between radiologists for all parameters of each ultrasonographic technique. High-definition flow was significantly superior to both CDU and PDU with respect to all analyzed items except the degree of flash artifacts (P < .05). With regard to flash artifacts, CDU was significantly better than either PDU or HDF. High-definition flow provided directional information, as did CDU.

The HDF technique provides better resolution for depicting hepatic vessels as well as their margins with less blooming compared with conventional Doppler ultrasonography in both native and transplanted liver. It also provides solid directional flow information. One point of concern, however, is the frequency of flash artifacts compared with that on CDU.

The objective of this study was to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) to characterize hypoechoic focal hepatic lesions (HFHL) in fatty liver (FL). A study group of 105 patients with FL and 105 HFHLs (52 malignant and 53 benign) underwent CEUS after SonoVue administration. Two blinded readers independently reviewed baseline ultrasound (US) and CEUS scans and classified each lesion as malignant or benign on a five-point scale of confidence, and recorded whether further imaging work-up was needed. Sensitivity, specificity, areas under the receiver operating characteristic (ROC) curve (A (z)), and interobserver agreement were calculated. We observed that the diagnostic confidence improved after reviewing CEUS scans for both readers (A (z)=0.706 and 0.999 and A (z)=0.665 and 0.990 at baseline US and CEUS, respectively; p<0.0001). Inter-reader agreement increased (weighted k=0.748 at baseline US vs. 0.882 at CEUS). For both readers, after CEUS, the occurrence of correctly characterized lesions increased (from 27/105 [27.5%] to 94/105 [89.5%], and from 19/105 [18.1%] to 93/105 [88.6%], respectively; p<0.0001) and the need for further imaging decreased (from 93/105 [88.6%] to 26/105 [24.8%], and from 96/105 [91.4%] to 40/105 [38.1%], respectively; p<0.0001). We conclude that CEUS improves the diagnostic performance of radiologists in the characterization of HFHLs in FL and reduces the need for further imaging work-up.

Nonmalignant liver masses are increasingly being recognized with the widespread use of imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging. The majority of these lesions are detected incidentally in asymptomatic patients. Based on the radiologic appearance, benign lesions can be categorized as solid or cystic, single or multiple, hypervascular or hypovascular. Based on histologic characteristics, they are classified as of hepatocellular, biliary, or mesenchymal origin. In the majority of patients, a proper diagnosis can be made based on these characteristics on imaging modalities alone. An invasive approach is seldom required. This review discusses the various characteristics of the most common benign liver lesions and recommends a practical approach.

We describe the spectrum of contrast-enhancement patterns of benign hepatic tumors arising in fatty liver on contrast-enhanced ultrasound (US).

Sixteen patients (12 women and four men) with 27 benign hepatic tumors (17 hemangiomas, eight focal nodular hyperplasias, and two hepatocellular adenomas) arising in fatty liver underwent baseline and pulse inversion US after administration of SonoVue. Two experienced radiologists evaluated baseline echogenicity and dynamic enhancement pattern of each lesion in comparison with adjacent liver parenchyma.

After administration of SonoVue, in the arterial phase 13 of 17 hemangiomas showed peripheral globular enhancement and one showed a rim of peripheral enhancement, followed by progressive centripetal fill-in, which was complete in 10 of 14 cases and incomplete in four. Three of 18 hemangiomas showed rapid and complete fill-in in the arterial phase. Eight of eight focal nodular hyperplasias became hyperechoic in comparison with adjacent liver parenchyma in the arterial phase and slightly hyperechoic or isoechoic in the portal venous and delayed phases. Both adenomas showed strong arterial contrast enhancement that became less intense in the portal venous and delayed phases.

Contrast-enhanced US after administration of SonoVue enables depiction of typical contrast-enhancement patterns in most benign hepatic tumors arising in fatty liver, thus providing useful clues for characterization.

Contrast-enhanced real-time low-mechanical-index sonography is a new diagnostic technique for the assessment of macro- and microcirculation. The purpose of our article is to describe contrast-enhancement patterns of different benign focal liver lesions using the second-generation contrast agent SonoVue and to compare these findings with those of gadobenate dimeglumine-enhanced MRI.

SonoVue-enhanced real-time low-mechanical-index sonography provides specific contrast-enhancement patterns of different benign focal liver lesions, allowing accurate characterization. Findings on SonoVue-enhanced sonography correlate well with those obtained on gadobenate dimeglumine-enhanced MRI.

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.

The objective of this study was to describe the spectrum of contrast-enhancement patterns of hepatic haemangiomas undetermined at grey-scale ultrasound (US) on SonoVue-enhanced pulse-inversion (PI) US. Twenty patients (11 women, nine men) with 35 haemangiomas (size range: 1-7 cm; mean: 3.1 cm) undetermined at baseline US underwent PI at low M.I. (0.05-0.08) after i.v. injection of SonoVue. All haemangiomas were confirmed by typical helical computed tomography (CT) and/or magnetic resonance imaging (MRI) findings. US examinations were videotaped and then reviewed by two experienced radiologists blinded to the final diagnosis. Readers evaluated by consensus the baseline echogenicity and the dynamic enhancement pattern of each lesion, in comparison with adjacent liver parenchyma. After administration of SonoVue, 31/35 (88%) haemangiomas showed peripheral hyperechoic nodules in the arterial phase, followed by progressive centripetal fill-in, which was complete in 25/35 cases and incomplete in 6/35 cases. Three out of 35 (9%) haemangiomas showed rapid and complete fill-in in the arterial phase, which persisted in the portal and delayed phases. Finally, 1/35 haemangiomas (3%) showed a rim of arterial contrast enhancement with progressive and complete centripetal fill-in in portal-venous and delayed phases. In conclusion, PI after the administration of SonoVue enabled the depiction of typical contrast-enhancement patterns in haemangiomas undetermined at baseline US.

We investigated whether observing the arterial vascularization of liver metastases by contrast-enhanced ultrasound with low mechanical index (low-MI) imaging offers additional diagnostic information for the characterization of the liver lesions.

Twenty nine patients with untreated liver metastases of different primaries were examined. Measurements were performed using a low frame rate, low-MI pulse inversion technique after injection of 2.4 mL SonoVue. The relative maximum signal intensity of the liver lesions related to the normal liver tissue was quantified. Ultrasound findings were compared with contrast-enhanced, dual-phase computed tomography (CT) using a pattern-based classification scheme.

Compared with contrast-enhanced CT, this modality better detects arterial perfusion. Metastases, even those usually considered hypovascularized, often showed homogeneous enhancement (66%) and higher arterial vascularization than normal liver tissue. CT did not show a comparable vascularization pattern (P < 0.001) or any similarly early signal intensity (P < 0.001).

Contrast-enhanced CT may not be able to visualize short-lasting but large differences of the arterial perfusion of liver metastases, as does contrast-enhanced low-MI ultrasound. This offers new methods for their characterization and for monitoring of therapeutic effects.

The aim of this study was to describe gray-scale appearance of liver parenchyma and focal nodular hyperplasia (FNH) by pulse inversion (PI) ultrasound (US) at baseline and after contrast agent administration in patients with normal and fatty liver. Sixteen consecutive patients (12 women, 4 men) with 29 previously diagnosed FNHs (15 of 29 located in normal liver and 14 of 29 in fatty liver) underwent PI US before and after SH U 508A (Levovist) injection. Signal intensity values were measured within the FNHs and the adjacent liver parenchyma in selected images. Baseline echogenicity of fatty liver was higher (15.19 +/- 2.90 dB +/- SD) than normal liver (10.91 +/- 3.15 dB +/- SD; p<0.001). After Levovist administration, normal livers (7 of 16) showed a statistically significant increase of echogenicity (16.59 +/- 3.81 dB +/- SD; p<0.001) in comparison with fatty livers (9 of 16; 15.75 +/- 3.12 dB +/- SD). The FNHs located in normal liver showed baseline echogenicity higher (12.29 +/- 3.22 dB +/- SD) than that of FNHs arising in fatty liver (7.06 +/- 2.43 dB +/- SD; p<0.001). After Levovist administration, FNHs located in normal liver showed a statistically significant increase of echogenicity (25.30 +/- 4.62 dB +/- SD) in comparison with FNHs located in fatty liver (13.58 +/- 3.54 dB +/- SD; p<0.001); the latter always showed mean values of echogenicity lower than surrounding liver parenchyma. In our series decreased contrast-enhancement pattern of both fatty liver and FNHs located in fatty liver was the most prominent finding when Levovist is administered. Contrast washout was a distinctive feature of FNH arising from the fatty liver.

To assess the value of SH U 508A-enhanced agent detection imaging in the characterization of focal hepatic lesions.

Contrast-enhanced agent detection imaging was performed on 78 focal hepatic lesions: 34 hepatocellular carcinomas, 22 metastases, 9 hemangiomas, 9 abscesses, 3 cysts, and 1 focal nodular hyperplasia. After administration of SH U 508A, interval delay scanning with agent detection imaging was performed with intervals of approximately 7 seconds (phase I), 30 seconds (phase II), and 90 seconds (phase III) after the first arrival of the contrast agent to the liver. Two observers blinded to the final diagnosis reviewed selected images and assessed the enhancement patterns of the lesions. For quantitative analysis, we calculated the enhancement ratio of the lesions and the difference of enhancement between the lesions and the liver parenchyma.

Agent detection imaging showed a distinctive enhancement pattern in focal liver lesions compared with that in the liver. Hepatocellular carcinomas were characterized by early enhancement (phase I) and washout (phases II and III; sensitivity, 94.1%; specificity, 93.2%; positive predictive value, 91.4%). Metastases showed peripheral rim or targetlike enhancement (phase I, phase II, or both) and a defect (phase III) and had sensitivity of 77.3%, specificity of 100%, and a positive predictive value of 100%. Hemangiomas showed peripheral nodular or inhomogeneous (phase I, phase II, or both) and gradually centripetal (phase II, phase III, or both) enhancement (sensitivity, 88.9%; specificity, 100%; positive predictive value, 100%). Abscesses were partially enhanced from phase I to phase III (sensitivity, 66.7%; specificity, 95%; positive predictive value, 85.7%). The results of the quantitative analysis of lesion enhancement were compatible with those of the qualitative analysis.

SH U 508A-enhanced agent detection imaging may yield distinctive enhancement characteristics in focal liver lesions that would contribute positively to the characterization of these hepatic lesions.

This study was performed to determine whether ultrasound (US) performed with SonoVue, a contrast agent that contains microbubbles filled with sulfur hexafluoride vapor, depicts differential patterns of contrast enhancement in focal hepatic lesions.

Forty focal hepatic lesions (15 hepatocellular carcinomas [HCCs], 10 metastases, 11 hemangiomas, and four focal nodular hyperplasias) in 39 patients were evaluated by means of US, color Doppler US, and contrast-enhanced US performed by using intermittent high-acoustic-power mode. Contrast-enhanced helical computed tomography (11 patients) and US-guided fine needle aspiration (28 patients) were used as reference procedures. Contrast enhancement patterns were defined by means of both subjective and objective analysis, and baseline and contrast-enhanced US scans were reviewed offline.

Thirteen of 15 HCCs, eight of 10 metastases, and all four hemangiomas with an atypical pattern at baseline US were correctly characterized after SonoVue injection. Two of 15 HCCs and two of 10 metastases remained indeterminate, with no characteristic baseline or contrast-enhanced patterns identified. Baseline US was essential in characterizing all hemangiomas with a typical pattern (n = 7), and color Doppler US with spectral analysis of tumoral vessels was essential in characterizing focal nodular hyperplasia. The percentage of diagnostic agreement with reference procedures was significantly increased (P < .001) for contrast-enhanced US compared with baseline US.

Characteristic patterns of US contrast enhancement with SonoVue help in characterizing and differentiating focal hepatic lesions.

To assess the feasibility of percutaneous biopsy of low-conspicuity focal liver lesions with use of pulse-inversion harmonic imaging (PIHI) guidance in the late phase after injection of microbubble contrast agent.

Twelve patients referred for ultrasound (US)-guided biopsy had liver lesions lacking adequate conspicuity to undergo biopsy under conventional ultrasound (US) guidance. They underwent biopsy procedures performed with the use of PIHI guidance in the late phase after injection of Levovist. The conspicuity of lesions, procedure time, number of passes, and success and complication rates were documented and compared to a control group. The control group consisted of retrospective analysis of 19 patients who had undergone conventional US-guided biopsy procedures performed by the same radiologist.

After contrast material injection, all lesions had sufficient increases in conspicuity to be targeted under PIHI guidance. Procedure time was prolonged in the PIHI group (66 minutes; range, 30-120 min; vs control, 33 min; range, 15-77 min; P <.01, Wilcoxon signed-rank test). The number of passes was greater in the PIHI group (1.9 +/- 0.3; vs control, 1.4 +/- 0.6; P <.01, chi(2) test). No statistically significant difference was observed when comparing success and complication rates.

PIHI in the late phase after injection of Levovist generated clear delineation of focal liver lesions in all cases, allowing an accurate and safe sampling. This technique broadens the scope of US-guided biopsy to lesions lacking adequate conspicuity on conventional US.

To evaluate the characterization of liver hemangiomas and malignant tumors using power Doppler sonography before and after intravenous injection of a sonocontrast agent.

Forty-five patients with 57 liver tumors (22 hemangiomas, 24 metastases, 10 hepatocellular carcinomas (HCC) and one cholangiocellular carcinoma) were examined prospectively. The distribution (peripheral, central, mosaic) and extent (none, minimal, moderate and strong) of intratumoral flow pattern in each sonographic examination was subjectively classified.

The administration of the sonocontrast agent by bolus injection caused enhancement to gradually increase up to 2 min and lasted for 4-5 min. After injection of contrast agent, flow signals appeared or increased in 34 tumors. No signal enhancement was observed in 18 hemangiomas, four metastases and one HCC. The sensitivity and specificity of intratumoral vascularity for the detection of malignant liver tumors was 37.1 and 90.9% for unenhanced power Doppler sonography, and 85.7 and 81.8% for contrast-enhanced power Doppler sonography, respectively.

Contrast-enhanced power Doppler sonography is superior to unenhanced power Doppler sonography in the demonstration of malignant tumor vascularity, and is helpful in differentiating between hemangiomas and malignant liver tumors. A specific flow pattern within the tumor is not established in primary and metastatic malignant tumors with contrast-enhanced power Doppler sonography.

The purpose of this study was to investigate whether late-phase pulse inversion harmonic imaging (PIHI) increases conspicuity in hepatic masses, helps to differentiate benign from malignant lesions, and demonstrates a greater number of and smaller metastatic lesions than do conventional (fundamental) sonography and helical CT.

Thirty patients (17 women and 13 men; age range, 35-77 years; mean age, 54 years) with known or suspected liver masses were evaluated using both fundamental sonography and contrast-enhanced PIHI during the liver-specific late phase of Levovist. The patients also underwent contrast-enhanced triphasic helical CT examinations within 1 week after sonography. In 4 of the patients, gadolinium-enhanced MRI was also performed as a part of their clinical work-up.

The increase in the lesions' conspicuity on PIHI compared with fundamental sonography was significantly greater in malignant lesions than in benign lesions (p< 0.001). An echogenic rim was observed on PIHI in 8 (53%) of 15 malignant lesions. The mean number of metastatic lesions visualized on PIHI (5.5 +/- 5.3) was significantly higher than the mean number visualized on fundamental sonography (2.5 +/- 2.1, p < 0.05). Although lesions as small as 3 mm were observed on PIHI, the mean sizes of the smallest lesions demonstrated using fundamental sonography, PIHI, and helical CT were not significantly different.

Late-phase PIHI is a useful technique for characterizing hepatic lesions and demonstrating both a greater number of and smaller metastases. It may help to differentiate benign from malignant liver masses and may obviate unnecessary and expensive further imaging.

To determine the accuracy of ultrasonography (US)-guided percutaneous biopsy in diagnosing malignant neoplasms for hepatic lesions 1 cm or smaller.

In this prospective study, 64 consecutive patients with 74 discrete focal hepatic lesions depicted at US were referred for liver biopsy to confirm the exact nature of the lesions. Mean lesion size was 0.84 cm +/- 0.13 (range, 0.5-1.0 cm). Biopsy was performed with an 18-gauge automated biopsy gun in 46 lesions (once [n = 37], twice [n = 7], three times [n = 2]) or a 22-gauge needle in 28 lesions (once [n = 23], twice [n = 4], three times [n = 1]). Measures were taken to ensure accurate and effective lesion sampling. The histologic diagnosis of malignant tumor and findings on follow-up US images of "benign" nodules for 15-39 months were the criterion standard.

No complications occurred. All specimens obtained were sufficient for diagnosis. Histologic examination revealed various types of primary and secondary malignant tumors (n = 44), hemangioma (n = 5), cirrhosis (n = 13), focal fatty change (n = 8), focal fatty sparing (n = 2), and abscess (n = 2). The diagnostic discrimination of US-guided biopsy in diagnosing malignant tumors in these small lesions was sensitivity, 98%; specificity, 100%; positive predictive value, 100%; negative predictive value, 97%; and accuracy, 99%.

Percutaneous biopsy under US control is highly accurate in providing a definitive histologic diagnosis of malignant neoplasms for small hepatic lesions if measures for ensuring precise and effective lesion sampling are taken.

The surgical and the radiological advances in liver tumors in last two decades have made some malignant tumors operable which were considered inoperable and have completely changed the expectations from radiology. However, accurate staging, that is performed by imaging modalities, has critical importance in the selection of patients who can benefit from resection. Radiologists and referring physicians, therefore, should be aware of the current concepts in imaging liver tumors. This report updates both the changing role of radiology in hepatic neoplasms and the appropriate use of radiological modalities in liver tumors.