Differential patterns of contrast enhancement in different focal liver lesions after injection of the microbubble US contrast agent SonoVue

PURPOSE: To identify differential contrast enhancement patterns in different focal hepatic lesions after injection of the microbubble contrast agent SonoVue using high or low acoustic power imaging. MATERIAL AND METHODS: Forty-seven focal hepatic lesions (1-8 cm) were detected in 45 patients at unenhanced gray-scale ultrasound (US) and evaluated by color Doppler (CD) US with spectral analysis of tumoral vessels. Lesions were subsequently evaluated by US contrast specific modes after IV bolus administration of 2,4-4,8 ml of SonoVue, by intermittent high acoustic power (18 patients) or by continous low acoustic power imaging (27 patients), during arterial, portal and late phase. Subjective evaluation of lesions appearance before and after SonoVue injection was performed. For final diagnosis multiphasic helical CT (21 patients) and/or fine needle US guided biopsy (24 patients) were considered as the reference procedures. RESULTS: Final diagnoses comprised 22 hepatocellular carcinomas (HCCs; 1,5-6 cm), 2 macroregenerative nodules (RNNs; 1-2 cm), 10 metastasis (2-3,5 cm), 10 hemangiomas (2-6 cm) and 3 focal nodular hyperplasias (FNHs; 1-3 cm). On CD evaluation HCCs revealed peripheral basket shaped (12/22) or intranodular (10/22) arterial pattern while, after SonoVue injection HCCs revealed diffuse contrast enhancement during arterial phase with contrast washout during portal and late phase. Metastases did not reveal flow signals on CD or contrast enhancement after SonoVue injection, except for 2 metastases which revealed peripheral and central vessels on CD and a diffuse contrast enhancement during arterial phase, appearing hypoechoic to the adjacent liver during portal and late phase. RNNs revealed dotted contrast-enhancement during portal and late phase with isoechoic appearance to the adjacent liver. Hemangiomas revealed some peripheral venous flows on CD and a peripheral nodular contrast enhancement during arterial phase with a centripetal fill-in during portal and late phase. FNHs revealed low resistance peripheral or central arterial vessels and a diffuse contrast enhancement during arterial phase, preceded or not by central spoke wheel shaped contrast enhancement, and a persistent iso-hyperechogenicity during portal and late phase. CONCLUSIONS: SonoVue injection has showed to identify differential contrast enhancement patterns in different focal hepatic lesions.     

Characterization of hypoechoic focal hepatic lesions in patients with fatty liver: diagnostic performance and confidence of contrast-enhanced ultrasound

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.     

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet.     

Characterisation of focal liver lesions undetermined at grey-scale US: contrast-enhanced US versus 64-row MDCT and MRI with liver-specific contrast agent

Purpose

The aim of this study was to assess the role of contrast-enhanced ultrasonography (CEUS) in the characterisation of focal liver lesions in comparison with multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) with liver-specific contrast agent.

Materials and methods

One hundred and eighty-seven focal liver lesions, 91 malignant and 96 benign (mean size 3.2 cm) — proved by biopsy (n=12), histology (n=4), MDCT (n=108), MRI (n=44) MDCT/MRI (n=19) — in 159 patients were studied by CEUS. Two expert radiologists consensually evaluated the contrast-enhancement patterns at CEUS. For each lesion, they assessed: (a) nature (benign, malignant, not assessable), (b) specific diagnosis and (c) need for further radiological evaluation. Sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CEUS were calculated.

Results

A total of 167/187 (89.3%) lesions were correctly assessed as benign or malignant at CEUS, whereas 14/187 (7.5%) lesions remained undetermined and 6/187 (3.2%) were incorrectly assessed. Sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CEUS were, respectively, 89%, 89.6%, 89%, 89.6% and 89.3%. The need for further radiological evaluation decreased to 46/187 (24.6%) lesions after CEUS (p<0.001).

Conclusions

In selected cases, CEUS can be considered an effective alternative to MDCT and MRI and reduce the need for further radiological workup.     

Bolus versus continuous infusion of microbubble contrast agent for liver US: initial experience

Institutional review board approval and informed consent were obtained. To prospectively assess if continuous infusion of galactose-palmitic acid can prolong the duration of hepatic enhancement at ultrasonography over bolus injection, 11 patients received two injections--one bolus injection (2 mL/sec) and one continuous infusion (1.5 mL/min)--with the same dose of galactose-palmitic acid (4 g, 300 mg/dL). Two unenhanced baseline sweep scans (mechanical index of 0.7 and 1.3) of the relevant liver lobe were acquired followed by contrast-enhanced sweeps after bolus injection and continuous infusion. Each sweep was saved as cine loops and analyzed with a personal computer. Duration of enhancement more than 3 dB was prolonged by continuous infusion from 4.3 minutes +/- 2.4 (+/-standard deviation) at bolus injection to 10.1 minutes +/- 3.0 (P < .005). Maximal parenchymal enhancement was 11.0 dB +/- 3.2 (bolus injection) and 9.2 dB +/- 3.8 (infusion, P < .05). Peak liver-to-lesion contrast was 14.2 dB +/- 6.3 (bolus injection) and 13.2 dB +/- 7.1 (infusion, not significant). Continuous infusion of galactose-palmitic acid markedly prolongs but slightly diminishes hepatic enhancement; liver-to-lesion contrast remains unchanged.     

Characterization of focal liver lesions with a new ultrasound contrast agent using continuous low acoustic power imaging: comparison with contrast enhanced spiral CT

PURPOSE: To evaluate the concordance of the enhancement patterns of a new ultrasound contrast agent (SonoVue) with those obtained with dual-phase contrast-enhanced spiral CT (CE-CT) in the characterization of focal liver lesions (FLLs). MATERIALS AND METHODS: Sixty-two patients with focal liver lesions discovered at ultrasound and also studied with CECT underwent contrast-enhanced ultrasound using continuous low acoustic power imaging after receiving a 2.4 ml bolus of the new US contrast agent SonoVue, consisting of a dispersion of sulphur hexafluoride microbubbles. The examinations were made using ATL HDI-5000, Acuson SEQUOIA and Aloka 5500 Prosound ultrasound systems with 5.2 MHz curved-array probes. The concordance between US and CE-CT images was evaluated on site by two radiologists blinded to CT RESULTS: The FLLs were assessed in the arterial (20 s after CM injection), portal (after 45-60 s) and late (after 120 s) phases for: 1) presence/absence of enhancement 2) distribution of enhancement (homogenous or target distribution, centripetal or centrifugal flow, and other), 3) qualitative enhancement pattern (hyperechoic, hypoechoic, or isoechoic) versus normal liver parenchyma. RESULTS: The concordance between SonoVue-enhanced US and CE-CT was 85%. Moreover during portal venous phase with CEUS it was possible to differentiate between malignancy or benignity of 91% of lesions. CONCLUSIONS: The preliminary data obtained in this study suggest that continuous low acoustic power imaging and contrast-enhanced US show similar results to CT in contrast distribution and contrast enhancement patterns.     

Twin fetuses: intravascular microbubble US contrast agent administration--early experience

PURPOSE: To explore the feasibility of administering SH U 508A by using a single-needle procedure at ultrasonography (US) in twin pregnancies to confirm interfetal transfusion in monochorionic twins and delineate placental angioarchitecture in pregnancies with twin-twin transfusion syndrome. MATERIALS AND METHODS: Fourteen twin pregnancies were studied over 12 months: seven with monochorionic twins, including six with twin-twin transfusion syndrome; two of unknown chorionicity; and five with known dichorionic twins discordant for fetal karyotype or anomaly and undergoing selective feticide in the third trimester. Bolus injection of 100 microL/kg of estimated fetoplacental weight of 400 mg/mL of SH U 508A was performed in the intrahepatic vein of one twin, and evidence of interfetal transfusion was sought by means of digital analysis of power Doppler signals in the contralateral twin. RESULTS: Contralateral twin echo enhancement was seen in four of the nine ultimately histopathologically proved monochorionic twins. As expected, no evidence of echo enhancement in the contralateral twin was seen in any of the five dichorionic twin pregnancies. There was no evidence of fetal compromise associated with the procedure. CONCLUSION: These pilot results suggest that microbubbles can be used to demonstrate interfetal transfusion but not to delineate placental vascular anatomy.     

Nonpalpable breast lesions: evaluation with power Doppler US and a microbubble contrast agent-initial experience

PURPOSE: To evaluate power Doppler ultrasonography (US) performed with a microbubble US contrast agent in the differentiation of nonpalpable breast lesions. MATERIALS AND METHODS: Fifty nonpalpable breast lesions in 50 patients were prospectively evaluated with power Doppler US before and after injection of the contrast agent SH U 508A. Lesion vascularity and the morphology of vessels on US scans were analyzed and were correlated with histologic results. RESULTS: Surgical excision revealed 22 cancers and 28 benign lesions. At nonenhanced power Doppler US, eight (36%) of 22 cancers and four (14%) of 28 benign lesions were vascular. At contrast agent-enhanced power Doppler US, 21 (95%) cancers and six (21%) benign lesions were vascular (P <.001). Irregular vessels were seen in three cancers and one benign lesion at nonenhanced power Doppler US and in 11 cancers and one benign lesion at contrast-enhanced power Doppler US. By using the presence of vascularity in the mass as the diagnostic criterion for malignancy, the sensitivity, specificity, and positive and negative predictive values of power Doppler US changed from 36%, 86%, 67%, and 63%, respectively, to 95%, 79%, 78%, and 96% after contrast agent injection. CONCLUSION: Contrast-enhanced power Doppler US was superior to nonenhanced power Doppler US in the demonstration and characterization of tumor vascularity in nonpalpable breast lesions. Contrast-enhanced power Doppler US may be useful for the differentiation between nonpalpable breast cancers and benign tumors.     

Characterization of focal liver lesions in real time using harmonic imaging with high mechanical index and contrast agent levovist

OBJECTIVE: The aim of this study was to characterize focal hepatic lesions using agent detection imaging and Levovist. MATERIALS AND METHODS: Sixty-five patients (21 male and 44 female; age range, 8-82 years; mean +/- standard deviation, 58.1 +/- 14.5 years) were independently evaluated by two observers in a blinded manner using stored sonographic images. Seventy-five lesions were found: 15 hepatocellular carcinomas, nine focal nodular hyperplasias, two adenomas, 21 hemangiomas, 23 metastases, and five regenerative nodules. Nine patients were excluded (six because of technical failures, three with unproven diagnoses). New high-mechanical-index software was used to reveal power harmonic responses from contrast microbubble destruction. After a venous bolus injection of 4 g of Levovist at a strength of 400 mg/mL, delayed imaging was used to study lesion enhancement in the arterial, portal, and parenchymal phases. Two comparisons were made. The first was between the B-mode image and the first contrast-enhanced image after the flash. The second was between color Doppler sonograms and real-time contrast-enhanced perfusion images. RESULTS: Contrast-enhanced images after the flash and real-time contrast-enhanced images revealed more information for the characterization of the lesion than did gray-scale and color Doppler images (p < 0.0001, Wilcoxon's signed rank test). Different types of lesions showed statistically significant differences in enhancement during each of the three vascular phases (p < 0.005, Kruskal-Wallis test). Lesions with lower contrast enhancement were metastases and regenerating nodules. Good agreement was present between the two observers; differences were not statistically significant (p > 0.05). CONCLUSION: Agent detection imaging with Levovist increased diagnostic confidence in the characterization of focal hepatic lesions as compared with standard sonography.     

B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans

Pulse- or phase-inversion ultrasonography (US) sums the signals returned from two 180 degrees ultrasound pulses. Linear scattering from tissue results in a signal void while nonlinear signals from microbubbles stand out. The technique was applied with a US contrast agent in 39 human subjects. B-mode enhancement of vessels and organ parenchyma was seen in all cases. Enhancement occurred from flowing and stationary microbubbles. The flow-independent enhancement of normal and abnormal tissue represents a major advance in contrast material-enhanced US with many potential applications especially in tumor imaging.     

Incidental focal solid liver lesions: diagnostic performance of contrast-enhanced ultrasound and MR imaging

Objective  

To prospectively assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) and MR imaging in incidental solid focal liver lesions not characterised on ultrasound.     

Liver lesions: intermittent second-harmonic gray-scale US can increase conspicuity with microbubble contrast material-early experience

The authors investigated the effect of intermittent second-harmonic gray-scale (ISHGS) ultrasonography (US) with SH U 508A microbubbles on the conspicuity of focal liver lesions. Twenty-three patients were included in the study. Images were analyzed subjectively and quantitatively. Objective lesion conspicuity was increased. In 12 of the 15 patients with liver malignancy, gray-scale defects were seen in previously unsuspected areas. ISHGS US may improve the sensitivity of US for liver lesions.     

彩色多普勒在肝脏占位性病变中的应用价值

肝脏占位性病变分为恶性与良性。因此,一旦发现肝内占位病变,良恶性的鉴别诊断就至关重要,其结果直接决定了治疗的方案及效果。超声诊断是目前肝脏影像学检测的首选方法。彩色多普勒是在二维扫描图像土叠加彩色血流信号,以利于快速评价血流信号的存在及血流方向,以及血管的空间分布,可以为临床提供有价值的诊断依据[1]。本文拟结合本院彩色多普勒的应用状况,探讨血流灌注指数（DPI）、门脉充血指数（PCI）和阻力比（RR）等血流参数在肝脏占位性病变诊断中的价值。     

Assessment of liver and kidney enhancement with a perfluorocarbon vapor-stabilized US contrast agent

RATIONALE AND OBJECTIVES: The authors evaluated the time-echogenicity response of liver, kidney, and implanted VX2 tumor after injection of a microbubble contrast medium and assessed use of an avascular lesion as an internal standard. MATERIALS AND METHODS: Twenty-one New Zealand White rabbits were studied. To evaluate use of an internal standard and the dose-response relationship, nine rabbits with 7-day-old avascular liver lesions created by alcohol ablation received 0.1, 0.25, 0.5, and 1.0 mL of AF0145, a microbubble contrast agent. To evaluate tumor echogenicity, 12 rabbits implanted with VX2 tumor in the liver (six also underwent alcohol ablation) received 0.5 mL of AF0145. Videodensitometry was used to analyze echogenicity changes over 10 minutes. RESULTS: Echogenicity of the alcohol-ablated liver was not affected by contrast material administration. Liver and kidney echogenicity relative to ablation increased linearly with dose, peaking 1 minute after injection and decaying to baseline over 9 minutes. Contrast material administration defined the size and margins of VX2 lesions more clearly. In the arterial phase, the tumor rim was hyperechoic relative to surrounding liver, becoming isoechoic during the portal venous phase then hypoechoic during the late phase parenchymal phase. CONCLUSIONS: Lesions created by alcohol ablation can be used as an internal standard for quantitative analysis of adjacent tissues. AF0145 enhances perfused tissues, including vascular tumors, at gray-scale, real-time ultrasonography and enhances the liver.     

B-mode enhancement of the liver with microbubble contrast agent: a blinded study in rabbits with VX2 tumors

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model. MATERIALS AND METHODS: A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard. RESULTS: Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification on precontrast images was poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader). CONCLUSION: AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.