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PubMed2003

Influence of contrast ultrasonography with perflutren lipid microspheres on microvessel injury.

Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting.

Animals↗

PubMed2000

Ultrasound contrast agents for echocardiography.

There is a need to monitor perfusion of the microcirculation in patients with minimal invasive approaches. The recent development of ultrasound contrast agents may open such an opportunity and permit to visualize online perfusion of cardiac muscle and other organs. An effective approach to achieve this objective is with gas filled microbubbles that provide strong ultrasound wave reflection and scatter. To interpret the ultrasound scattering profiles, it is necessary to understand the transport of microbubbles in the microcirculation, specifically their transport in blood stream, the attachment to blood cells and endothelium, as well as possible leakage across the microvascular wall. Each of these events provides an opportunity to monitor with ultrasound not only microvascular blood flow but also detect inflammatory sites in the circulation.

Journal Article↗

PubMed1986

Importance of adequate gas-mixing in contrast echocardiography.

Microbubble formation has been accepted as the mechanism producing contrast echoes. Comparisons of the contrast effects of various agents have been studied extensively, but the importance of gas-mixing has been less appreciated. To test the hypothesis that good gas-mixing, by facilitating microbubble formation, would enhance contrast effect, this study compared the contrast echocardiograms of ten adult patients before and after mixing carbon dioxide with various contrast agents. Contrast agents tested included a 5 percent glucose in water, vitamin B complex, vitamin C, and Cardiogreen solutions. First, we recorded echocardiograms by injecting each diluted contrast solution alone, then repeated the examinations using 10 ml of each diluted solution with 1 ml of carbon dioxide (CO2), mixed by means of a four-way stopcock. Satisfactory or excellent results were obtained in seven of ten, ten of ten, ten of ten, and ten of ten tests, respectively, after thorough gas-mixing, vs one of ten, seven of ten, eight of ten, and six of ten, respectively, before gas-mixing. We conclude that the addition of sufficient amounts of gas, followed by thorough mixing, is of great importance in contrast echocardiography. Consistently good results can be achieved with vitamin C, vitamin B or Cardiogreen solutions by this simple and safe method.

Adolescent↗

PubMed1993

[A simple test procedure for detection of micro-bubbles in extracorporeal blood circulation].

A new contrast medium for the ultrasonic examination of the human heart was recently approved by the German medical authorities. It has proved useful for investigating the sensitivity of air detectors in detecting microbubbles measuring only a few microns in the extracorporeal line. Although the contrast medium, originally intended to be injected undiluted into the human blood circulation, was considerably diluted, microbubbles were detected by the ultrasonic air detector far below the danger limit.

Embolism, Air↗

PubMed1986

Assessment of ventricular shunt patency by sonography: a new noninvasive test.

This report describes a new test of patency of the ventricular component of a ventriculoperitoneal shunt that precludes injection into the shunt reservoir. Preliminary clinical experience confirms that digital compression of the ventricular shunt reservoir (Cordis standard and pediatric reservoir), while occluding the shunt distal to the reservoir, generates microbubbles that increase the echogenicity of the catheter, demonstrating shunt patency. In vitro, the extrusion of microbubbles from catheter side holes can be imaged during digital compression of the reservoir, but so far this has not been imaged in patients as a direct sign of shunt patency. A sonographic means of assessing shunt function offers the advantage of simultaneously imaging the ventricular catheter, determining its location, and assessing the etiology of shunt failure. Its usefulness is limited to pediatric cases in which an adequate transfontanelle cranial sonographic study can be obtained and to individuals with large craniotomy defects.

Adolescent↗

PubMed2001

Contrast-enhanced harmonic imaging for the diagnosis of vesicoureteral reflux in pediatric patients.

OBJECTIVE: Harmonic imaging using phase or pulse inversion technology is a new sonographic diagnostic modality that has the potential to produce images of a higher quality than can be obtained with the conventional method. The aim of this study was to compare both types of harmonic modalities--tissue and contrast harmonic imaging--with the fundamental imaging mode in contrast-enhanced B-mode sonographic diagnosis of vesicoureteral reflux. SUBJECTS AND METHODS: Fifty-four children presenting for diagnostic examination of vesicoureteral reflux underwent standard sonography of the urinary tract in the fundamental mode, followed by intravesical administration of a galactose-based contrast medium containing microbubbles. The contrast-enhanced sonography was conducted by scanning the bladder and each kidney in transverse and longitudinal planes, from ventral and dorsal views, consecutively in B-mode using fundamental, contrast harmonic, and tissue harmonic imaging modalities. Soft-touch buttons on the console screen were used to alternate between the three imaging options, so that switching from one modality to the other could be done almost instantaneously. For comparison, in each patient, we selected one set of contrast-enhanced images of the bladder and two sets, one ventral and one dorsal, of the kidney. In a series, the images were compared and ranked from 1 to 3, with 1 being the best, with regard to sonomorphology (demarcation of the retrovesical space and renal pelvis as the potential sites to look for vesicoureteral reflux) and reflux detection and conspicuity, if present. RESULTS: In all, 248 sets of images were available for comparison. The delineation of both the retrovesical space and the renal pelvis was found to be best with tissue harmonic imaging in 84% and 96% of the image sets, respectively (p < 0.01). Forty-one sets of images were compared from 27 kidney-ureter image units of 22 children (41%) with reflux. The refluxing microbubbles were much more conspicuous in the harmonic imaging mode (tissue harmonic, 100%; contrast harmonic, 93%) than in the fundamental mode (p < 0.01). In eight kidney-ureter units, the reflux was detected only by using the harmonic imaging modalities. CONCLUSION: Visualization of the urinary tract and detection of ultrasound contrast media is significantly improved by the use of the harmonic imaging modalities. When both fundamental and harmonic imaging options are available, we recommend harmonic imaging for contrast-enhanced sonographic diagnosis of vesicoureteral reflux.

Adolescent↗

PubMed2001

Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment.

Despite intensive study, the relation between insulin's action on blood flow and glucose metabolism remains unclear. Insulin-induced changes in microvascular perfusion, independent from effects on total blood flow, could be an important variable contributing to insulin's metabolic action. We hypothesized that modest, physiologic increments in plasma insulin concentration alter microvascular perfusion in human skeletal muscle and that these changes can be assessed using contrast-enhanced ultrasound (CEU), a validated method for quantifying flow by measurement of microvascular blood volume (MBV) and microvascular flow velocity (MFV). In the first protocol, 10 healthy, fasting adults received insulin (0.05 mU. kg(-1). min(-1)) via a brachial artery for 4 h under euglycemic conditions. At baseline and after insulin infusion, MBV and MFV were measured by CEU during continuous intravenous infusion of albumin microbubbles with intermittent harmonic ultrasound imaging of the forearm deep flexor muscles. In the second protocol, 17 healthy, fasting adults received a 4-h infusion of either insulin (0.1 mU. kg(-1). min(-1), n = 9) or saline (n = 8) via a brachial artery. Microvascular volume was assessed in these subjects by an alternate CEU technique using an intra-arterial bolus injection of albumin microbubbles at baseline and after the 4-h infusion. With both protocols, muscle glucose uptake, plasma insulin concentration, and total blood flow to the forearm were measured at each stage. In protocol 2 subjects, tissue extraction of 1-methylxanthine (1-MX) was measured as an index of perfused capillary volume. Caffeine, which produces 1-MX as a metabolite, was administered to these subjects before the study to raise plasma 1-MX levels. In protocol 1 subjects, insulin increased muscle glucose uptake (180%, P < 0.05) and MBV (54%, P < 0.01) and decreased MFV (-42%, P = 0.07) in the absence of significant changes in total forearm blood flow. In protocol 2 subjects, insulin increased glucose uptake (220%, P < 0.01) and microvascular volume (45%, P < 0.05) with an associated moderate increase in total forearm blood flow (P < 0.05). Using forearm 1-MX extraction, we observed a trend, though not significant, toward increasing capillary volume in the insulin-treated subjects. In conclusion, modest physiologic increments in plasma insulin concentration increased microvascular blood volume, indicating altered microvascular perfusion consistent with a mechanism of capillary recruitment. The increases in microvascular (capillary) volume (despite unchanged total blood flow) indicate that the relation between insulin's vascular and metabolic actions cannot be fully understood using measurements of bulk blood flow alone.

Adult↗

PubMed1992

Response of the rabbit lung as a criterion of safety for fluorocarbon breathing and blood substitutes.

From the first liquid breathing experiments until now, the lung, not surprisingly, has played a central role in the evolution of fluorocarbon blood substitutes. The first breathable fluorocarbon, a mixture of F-alkylfurans(FC75), bp 102 degrees C, while a poor solvent for the lung's lining and a good solvent for oxygen and carbon dioxide, proved to cause a characteristic gas/vapor microbubble embolism following intravenous administration as an emulsion. Higher boiling fluorocarbons, e.g. F-tributylamine (FC47), bp 174 degrees C, do not produce such gas-vapor emboli. However, intermediate boiling compounds such as F-decalin (PP5), bp 141 degrees C, produce lungs which, although they certainly appear not to contain microbubble emboli, do not collapse when the thorax is opened. Such hyperinflated non-collapsible lungs (HNCL) occur in the rabbit after the intravenous infusion of F-decalin emulsions as well as after the intratracheal infusion of F-decalin neat liquid. F-decalin induced HNCL retain their appearance and low specific gravity for many weeks, gradually returning toward normal after many months. F-methyl decalin, bp 165 degrees C, does not cause HNCL after intravascular or intratracheal administration. Fluorocarbons having boiling points between 140 degrees C and 165 degrees C are being tested in order to find a perfluorinate with the highest transpiration rate, and hence vapor pressure, compatible with an acceptable body dwell time. We have given fluorocarbons intratracheally to 75, intravenously to 221 and both intratracheally and intravenously to 8 rabbits. Free radical trapping agents, antineutrophil, antiinflammatory and other drugs have been administered without appreciable decrease of HNCL. Fluorocarbon critical solution temperature, lipid solubility, emulsifiability, and other physicochemical properties may mediate the pulmonary effect. One method of preventing and treating low dose F-decalin-induced HNCL in rabbits is described.

Animals↗

PubMed1994

Artifacts in ultrasonic contrast agent studies.

Intravenously injected ultrasonic contrast agents making use of encapsulated gas microbubbles have excellent clinical potential for both color and spectral Doppler studies. However, a number of artifacts are associated with sonographic contrast agent measurements. Three artifacts were identified: (1) color "blooming," (2) increased maximum Doppler shift, and (3) spectral "bubble noise." Experiments have been conducted with Albunex and Levovist. These agents were injected into rabbits and humans to allow the cause of the artifacts to be established. Color blooming occurs soon after the bolus injection and is seen as gray scale pixels changing to color display. This is caused by the increase in flow signal strength. The apparent increase in the maximum Doppler shift frequency is due to the limited dynamic range of the spectral display. Only signals above a certain threshold are visible. As the Doppler signal power is enhanced, the highest frequency visible also increases. Finally, very large excursions can sometimes be seen in the spectral display (bubble noise). These might be due to either the breakdown of microbubbles or individual very large bubbles. The color blooming and bubble noise artifacts are easily identifiable and will not influence diagnostic management. The increase in peak Doppler shifts is more troublesome as it prevents comparison of spectral parameters obtained before and after injection of contrast agent.

Albumins↗

PubMed2002

Arrhythmias in rat hearts exposed to pulsed ultrasound after intravenous injection of a contrast agent.

OBJECTIVE: To develop an animal model suitable for characterizing electrocardiographic arrhythmias in hearts exposed to ultrasound after injection of a microbubble contrast agent. METHODS: Conduction complex and heart lesion data were recorded from 20 rats that received intravenous injections of 0.25 mL of a contrast agent and were exposed to pulsed ultrasound (frequency, 3.1 MHz; pulse duration, 1.3 microseconds; pulse repetition frequency, 1700 Hz; and in situ peak rarefactional pressure, 15.9 MPa). The volume of the contrast agent based on body weight and the mechanical index (ultrasonic pressure) exceeded those used in echocardiography by 14 to 345 and 3 to 29 times, respectively. RESULTS: Premature atrial complexes, premature ventricular complexes, or polymorphic ventricular tachycardia occurred in 10 rats. When ultrasound exposure was halted, arrhythmias ceased but reoccurred in 4 of the 10 rats when exposure resumed. Myocardial degeneration identified by histochemical staining (hematoxylin-basic fuchsinpicric acid) was observed in 16 rats; however, only 10 rats had arrhythmias. There was no significant difference in the amount of histochemical staining in hearts from rats with arrhythmias when compared with rats without arrhythmias. CONCLUSIONS: An animal model suitable for characterizing electrocardiographic arrhythmias in rat hearts exposed to ultrasound after injection of a microbubble contrast agent was developed. Because arrhythmias were induced principally when the contrast agent interacted with ultrasound during exposure, the presence of myocardial degeneration alone was not a sufficient explanation for ectopic electrical activity. Under these extreme exposure conditions, the data suggest that pulsed ultrasound through its biomechanical interactions with contrast agents has the potential to induce arrhythmias.

Albumins↗

PubMed1999

[Contrast media in ultrasonography].

Microbubbles of air or other gases are ideally suited as echo-enhancers because of the high difference in acoustic impedance of gas/fluid interfaces. The microbubbles are 1-7 microns in diameter and capable of surviving pulmonary passage to produce enhancement of especially the Doppler signal after intravenous injection. The main clinical role of ultrasound (US)-contrast is to enhance the Doppler signals (up to 20 dB) in inconclusive Doppler examinations. Experience with US-contrast agents comes mainly from use of the galactose based agent Levovist (Schering AG, Germany). The US-contrast agents have further properties: a) Air bubbles in the sound fields will reverberate and return sound with harmonic frequencies. This phenomenon can be used in "harmonic imaging". B) Short intense sound impulses will destroy the bubbles resulting in a mosaic of colours (stimulated acoustic emission). This phenomenon may be used in tumour diagnostics in the liver.

Acoustics↗

PubMed1999

[Contrast agents in echocardiography].

Contrast echocardiography is new imaging modality dynamically entering to clinical practice. The efficient application of the contrast agents needs some knowledge of microbubbles physics. In this paper the basic principles of echo-contrast effects are presented and ultrasound microbubble fluid dynamics in the ultrasonic pressure field is addressed briefly. The recent developments in harmonic imaging end the transient and non-linear acoustic phenomena allow ultrasound to detect of blood flow in the microcirculation. In the second part of the paper it was demonstrated a potential for myocardial opacification by contrast echocardiography and the more recent application such as myocardial perfusion. The authors also reported intracardiac shunts imaging, enhancing endocardial border definition and bringing out of weak Doppler signals. The review of new contrast agents coming to the clinical practice is presented.

Contrast Media↗

PubMed2001

[Brain perfusion ultrasound in atherosclerotic disease. Work in progress].

AIM: The use of low frequency probes allows to overcome the resistance of the skull and evaluate Willis's circle by B-mode and Trans-Cranial Color-Doppler (TCCD) to obtain morphological and functional information related to brain circulation during pathologic conditions. With the new software available today modern technology allow us to measure the transient scattering produced by the rupture of the contrast medium microbubbles and estimate the presence of the contrast medium both in macro- and microcircle. In this way it is possible to appraise parenchymal perfusion. This study aims to assess the intracranial micro- and macrocircle using TCCD with contrast medium (Levovist) and to compare the results with the patients' clinical signs. MATERIAL AND METHODS: We studied 21 subjects aged 45-73 years (mean 68 years) with atheromatous uncomplicated plaques in the internal carotid artery producing varying degrees of stenosis and 10 healthy controls. The examinations were performed using an ATL HDI 3000 ultrasound machine with a Phased Array 3.25 MHz probe. The mechanic index was calibrated to high values to obtain rupture of the microbubbles under insonation. Intensity/time curves of transient scattering were extrapolated for both the cerebral macrocircle and the parenchymal microcircle in the region of interest. RESULTS: The curves were compared with the clinical presentation of the different classes of patients and the results obtained were consistent in showing a clinical pattern of perfusional deficit in subjects with symptoms of chronic brain ischemia. In particular, it was possible to compare the morphologic data relative to the contrast medium decay curves with the patient's clinical condition, confirming the suspicion of cerebral microcircle pathology. CONCLUSION: Thanks to improvements in the software and to the definition of effective algorithms, contrast-enhanced TCCD will be able to provide information on brain perfusion in a simple, inexpensive and relatively non-invasive manner.

Adult↗

PubMedDate not supplied

[Current role of color Doppler ultrasound in acute renal failure].

Acute Renal Failure (ARF) is characterized by a rapid decline of the glomerular filtration rate, due to hypotension (prerenal ARF), obstruction of the urinary tract (post-renal ARF) or renal parenchymal disease (renal ARF). The differential diagnosis among different causes of ARF is based on anamnesis, clinical symptoms and laboratory data. Usually ultrasound (US) is the only imaging examination performed in these patients, because it is safe and readily available. In patients with ARF gray scale US is usually performed to rule out obstruction since it is highly sensitive to recognize hydronephrosis. Patients with renal ARF have no specific changes in renal morphology. The size of the kidneys is usually normal or increased, with smooth margins. Detection of small kidneys suggests underlying chronic renal pathology and worse prognosis. Echogenicity and parenchymal thickness are usually normal, but in some cases there are hyperechogenic kidneys, increased parenchymal thickness and increased cortico-medullary differentiation. Evaluation of renal vasculature with pulsed Doppler US is useful in the differential diagnosis between prerenal ARF and acute tubular necrosis (ATN), and in the diagnosis of renal obstruction. Latest generation US apparatus allow color Doppler and power Doppler evaluation of renal vasculature up to the interlobular vessels. A significant, but non specific, reduction in renal perfusion is usually appreciable in the patients with ARF. There are renal pathologic conditions presenting with ARF in which color Doppler US provides more specific morphologic and functional information. In particular, color Doppler US often provides direct or indirect signs which can lead to the right diagnosis in old patients with chronic renal insufficiency complicated with ARF, in patients with acute pyelonephritis, hepatic disease, vasculitis, thrombotic microangiopathies, and in patients with acute thrombosis of the renal artery and vein. Contrast enhanced US is another useful diagnostic tool in patients with ARF which has been recently introduced in clinical practice. Microbubble administration may reduce technical failure in the evaluation of the renal artery. Moreover, perfusion defects due to stenosis or thrombosis of the renal segmentary vessels are better recognized. New diagnostic possibilities of enhanced US include evaluation of both cortical and medullar vessels, and functional evaluation of renal perfusion. Measuring the transit time of the microbubbles is useful for the diagnosis of renal artery stenosis and, in transplanted kidneys, for differential diagnosis between ATN and acute rejection.

Acute Kidney Injury↗

PubMed2001

[An autopsy case of an infant born with a caul who died due to asphyxia after live-birth].

We reported an autopsy case of a child born with a caul. The infant was a female and seemed to be full-term. No remarkable pathological findings for disease or anomalies were observed. The floating test of lungs was partially positive. And on the gastro-intestinal floating test, only stomach floated. In histological examination, the alveoli in the lungs were partially slightly open. We thought that those were due to the cardio-pulmonary resuscitation. Pulmonary surfactant was positive immunohistochemically. And the stable microbubble test on the liquid in her stomach was very strong. Even if a child is born alive, he or she will soon die due to asphyxia but for the production of surfactant in the lungs. We can evaluate more precisely the potential respiratory ability of a neonate died due to asphyxia by means of stable microbubble test on newborn gastric contents and immunohistochemical staining of surfactant in lungs.

Asphyxia Neonatorum↗

PubMed2002

Ultrasound increases plasmid-mediated gene transfer to dystrophic muscles without collateral damage.

Studies have shown that ultrasound, used either alone or in combination with microbubble contrast agents, can increase cell membrane permeability to plasmid DNA. Because ultrasound is a non-painful and well-established tool in clinical medicine, its potential to enhance DNA uptake into the muscles of patients with muscular dystrophy is conceptually attractive. Therefore, we evaluated the ability of ultrasound pulses (1 MHz; 1.5 W/cm2) to increase exogenous (LacZ) gene expression in normal wild-type and dystrophic Dmd(mdx/mdx) mice after plasmid DNA injection into muscle. We also ascertained whether co-injection of lipid-encapsulated perfluoropropane microbubbles (Definity) or pretreatment with hyaluronidase could further increase the level of gene transfer to ultrasound-treated muscles. The use of ultrasound did not increase transfection efficiency in normal mice. In contrast, dystrophic mice demonstrated an increase in the number of transfected fibers (threefold) as well as the amount of LacZ protein (22-fold) after ultrasound exposure, provided that Definity was also co-injected with the DNA. Pretreatment of muscles with hyaluronidase before ultrasound exposure was not effective in augmenting the level of gene transfer. Under the optimal conditions for dystrophic muscle transfection (ultrasound + Definity), there was no associated increase in muscle damage. Hence ultrasound may provide a safe and effective method for enhancing gene transfer to dystrophic muscles, thereby increasing the prospects for therapeutic application of naked DNA in muscular dystrophy patients.

Animals↗

PubMed1992

[Assessment of fetal lung maturity using newly developed immunological measurement of fetal pulmonary surfactant apoprotein-A in amniotic fluid].

The level of immunoreactive lung surfactant apoprotein A (SP-A) was determined with a newly developed one-step ELISA kit (TDR-20) in 217 samples obtained by transabdominal or transvaginal amniocentesis from 217 pregnant women with high risk pregnancy. The lecithin/sphingomyelin ratio (L/S ratio) by two-dimensional thin layer chromatography, disaturated phosphatidylcholine (DSPC) values, shake test and the stable microbubble method were done simultaneously to compare diagnostic reliability in estimating fetal lung maturity. Amniotic fluid SP-A levels increased with advancing gestational age and correlated well with the values obtained by the other methods. When the cut-off SP-A value for the assessment of lung maturity was set at 1,700ng/ml in the amniotic fluid obtained within 24h before delivery, the true-negative rate for RDS was 71% and the true-positive rate for non-RDS was 83%. The sensitivity, specificity and accuracy were 100%, 83% and 88%, respectively. These results are comparable with those for the L/S ratio, DSPC determination and the stable microbubble method, and were slightly better than those for the shake test. In conclusion, this newly developed ELISA kit for the measurement of amniotic fluid SP-A is more effective than other methods currently available for the evaluation of fetal lung maturity, when it is considered that it requires only 0.2ml of amniotic fluid and provides results in only 2h without technical difficulties.

Amniotic Fluid↗

PubMedDate not supplied

Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture.

BACKGROUND/AIMS: Although endoscopic ultrasonography is considered the most useful diagnostic modality for the regional staging, the capability of diagnosing lymph node metastasis based on endoscopic ultrasonography images alone is not sufficient. To improve the capability of differential diagnosis of lymph node enlargement, contrast-enhanced echolymphography was performed using endoscopic ultrasonography-guided puncture. METHODOLOGY: Contrast-enhanced echolymphography was performed in 8 metastatic lymph nodes surgically resected from patients with gastrointestinal cancers (in vitro study) and also in 55 patients in whom abdominal lymph node swelling was indicated by endoscopic ultrasonography (in vivo study). Lymph nodes were punctured under real-time endoscopic ultrasonography guidance, and carbon dioxide microbubbles were injected to evaluate echo features before and after microbubbles injection. RESULTS: Contrast-enhanced echolymphography of freshly resected metastatic lymph nodes showed nonhomogeneous echo patterns. In regions demonstrating filling defects detected by contrast-enhanced echolymphography, neoplastic infiltration was pathologically observed. In almost all of the malignant lymph nodes studied in vivo, filling defects and heterogeneous enhancements were observed by contrast-enhanced echolymphography. However, contrast-enhanced echolymphography demonstrated uniform patterns in most of the benign group. The sensitivity, specificity, positive and negative predictive value, and accuracy of differential diagnosis by contrast-enhanced echolymphography were 95.8%, 90.3%, 88.5%, 96.6%, and 92.7%, respectively. CONCLUSIONS: Contrast-enhanced echolymphography is a useful method for help in the differentiation between reactive and malignant alterations of lymph nodes.

Adult↗