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PubMed2000

Myocardial contrast echocardiography: clinical benefit and practical issues.

Real-time bedside evaluation of myocardial perfusion after intravenous application of microbubbles is the ultimate goal for contrast echocardiography. Over the past decade rapid evolution has occurred in the development of contrast agents, ultrasound equipment tailored to their detection, and image interpretation. This article offers a review of the basic concepts of the technique's background, contrast agent design, and imaging technology. The major clinical indications of myocardial contrast echocardiography are evaluation of acute ischemic syndromes, diagnosis of viable myocardium following AMI, and the detection of CAD using stress contrast perfusion imaging. Furthermore, the article addresses the most significant practical problems and suggested solutions to master those problems. As major new achievements are realistic expectations for the first decade of the twenty-first century, we conclude that the coupling of a new generation of contrast agents with innovative echocardiographic instrumentation will ultimately enable the full potential of myocardial contrast echocardiography to be realized which may revolutionize modern echocardiography.

Acute Disease↗

PubMed2000

Contrast echocardiography: clinical utility.

This article reviews the advances made by the echocardiographic contrast agents from their first appearance in the early 1970s with homemade preparations up to the new generation of transpulmonary contrast agents made of small microbubbles capable of transversing the lung's capillary bed. The great progress in contrast agent development has kept pace with the progress made by echocardiographic equipment, thus making the study of myocardial perfusion in the clinical settings a near-future reality. This article also discusses the medical need that myocardial contrast echo has the potential to satisfy.

Contrast Media↗

PubMed1993

Identifying stunned myocardium during cardiac surgery: the role of myocardial contrast echocardiography.

Differentiation of reversibly stunned myocardium from irreversibly damaged (infarcted) myocardium is critically important in patient management. Current methods for monitoring myocardial function yield only nonspecific assessments of myocardial viability. On the other hand, myocardial contrast echocardiography (MCE) can be used to evaluate the extent of myocardial perfusion as well as the efficacy of myocardial protection in patients undergoing coronary artery bypass graft (CABG). This system includes an external ultrasound unit and an internal tracer, usually gaseous microbubbles, which reflect the ultrasonic beam. Previous studies have shown that myocardial risk areas identified with MCE correlate with areas defined by technetium autoradiography and infarction size. We have used MCE to evaluate coronary artery bypass patients (N = 21) with regard to myocardial function and cardioplegia perfusion patterns. A significant correlation (p < 0.01) was found between abnormal contrast enhanced cardioplegia patterns and depression of left ventricular function. Refinements to ultrasound technology and contrast agents will further enhance the diagnostic power of MCE for the quantification of myocardial blood flow.

Cardiac Surgical Procedures↗

PubMed2001

Ultrasonic assessment of physiological echo-contrast agent distribution in brain parenchyma with transient response second harmonic imaging.

OBJECTIVES: The present study was designed to provide normal data of transient response second harmonic imaging (TRSHI) examinations of cerebral echo contrast enhancement using different modes of electrocardiogram (ECG) gating and echo-contrast agent doses. MATERIALS AND METHODS: Fifty-five patients were examined in an axial diencephalic plane of section using the transtemporal acoustic bone window. TRSHI examinations (ECG gating: systolic, frame-rate once every 2 cardiac cycles = "basical instrument setting") could be performed in 50 individuals with adequate insonation conditions after application of 4 g of a galactose-based microbubbles suspension in a concentration of 400 mg/ml. For comparison, diastolic ECG gating (20 patients), cardiac-cycle triggering frequency of once every 2 seconds (15 patients), or an echo contrast agent dose of 2 g Levovist (15 patients) were used. Analysis of peak intensities (PIs) and areas under the curve (AUCs) was done in posterior (region of interest [ROI]a) and anterior (ROIb) parts of the thalamus, in the lentiform nucleus (ROIc), and the white matter (ROId). RESULTS: In 41 patients with basical instrument setting, characteristic time intensity curve (TIC) could be detected in all ROIs. In ROIa (90%) and ROIb (82%), focal contrast enhancement was most difficult to visualize, and in ROIc and ROId, characteristic TICs were observable in more than 90% of the examinations. Background subtracted PIs and AUCs were significantly higher in ROIc (mean PI: 12.2 +/- 8 acoustic units [AUs]; mean AUC: 598.8 +/- 451.1 AU x Cardiac cycles), and ROId (11.8 +/- 6.9; 559.2 +/- 404) as compared to ROIa (8.3 +/- 5.2; 368.9 +/- 242.7) and ROIb (7.1 +/- 4.7; 298.2 +/- 199.1) (P < .0001). Values for corresponding examinations with a diastolic ECG gating and a cardiac cycle triggering frequency of once every 2 seconds were not different as compared to the basical instrument setting. A 4 g Levovist dose increased the portion of typical TIC in all ROIs. PI of 4 g examinations were significantly higher in ROId and ROIb as compared to the 2 g examination. CONCLUSION: Our findings indicate that TRSHI allows noninvasive assessment of focal cerebral contrast enhancement in the majority of patients with adequate insonation conditions. This study provides data about normal quantitative and qualitative TRSHI values in patients without cerebrovascular diseases. A dose of 4 g Levovist is recommended in those individuals with inaccurate echo contrast enhancement using the 2 g dose.

Adult↗

PubMed2001

Pharmacokinetics of echocontrast agent infusion in a dog model.

Ultrasound contrast agents (UCAs) have a distinct diagnostic impact on transcranial Doppler (TCD) and duplex sonography. In addition to the properties of the UCA and ultrasound imaging modes, the duration of contrast enhancement depends on the administration mode. Infusion of UCAs may be appropriate for prolonging the diagnostically useful time of elevated Doppler intensity. Five sedated dogs were investigated by TCD during infusion with SonoVue, a new UCA consisting of sulfur hexafluoride microbubbles. The infusion rate was varied, and the time-intensity curves were analyzed. Infusion rate of 70 ml/h provided a stable mean level of increased Doppler intensity up to 24 to 26 dB over baseline, whereas a rate of 35 ml/h did not result in a stable plateau (range 8-19 dB over baseline [5 minutes after starting time]). The maximum increases in Doppler mean intensity (18.2 dB [35 ml/h] and 25.6 dB [70 ml/h]) were significantly different (P = .025). Pharmacokinetic analysis of SonoVue during inflow (by exponential functional fitting of the time-mean intensity curves) and elimination (by linear regression analysis) revealed no dose-related differences. This study demonstrated a dose-dependent level of increased Doppler mean intensity within the brain circulation during infusion of SonoVue. Unlike the bell-shaped course of Doppler signal enhancement seen after bolus injection, infusion generates a stable plateau, which is an important prerequisite for more advanced contrast applications.

Analysis of Variance↗

PubMed2001

Comparison between color power Doppler ultrasound with echo-enhancer and spiral computed tomography in the evaluation of hepatocellular carcinoma vascularization before and after ablation procedures.

OBJECTIVE: Use of new echo enhancers capable of passing the lung filter has extended the clinical applications of color power Doppler flow imaging in many diseases and appears promising in the study of neoplasm vascularization. Levovist (Shering, Berlin Germany) is an ultrasound contrast agent containing galactose microbubbles suspended in palmitic oil. The sensitivity of Levovist-enhanced color power Doppler was compared to that of standard color power Doppler and contrast-enhanced spiral computed tomography (CT) in the detection of vascular signals in hepatocellular carcinoma. METHODS: We examined 29 hepatocellular carcinoma nodules in cirrhotic livers that had appeared avascular on unenhanced color power Doppler. Color power Doppler studies were repeated with and without Levovist enhancement before (15 examinations) and/or after (23 examinations) percutaneous ablation procedures. Findings (vascularized vs nonvascularized) were compared to those obtained with contrast-enhanced spiral computed tomography (gold standard) performed no more than 24 h after each of the 38 Doppler examinations. RESULTS: In pretreatment studies, Levovist-enhanced power Doppler correctly revealed vascularization in 12 of 15 lesions that had appeared avascular without echo enhancement and confirmed the avascularity of one other nodule; the remaining two, which appeared avascular on contrast-enhanced Doppler, displayed vascularization on the spiral CT examination. Levovist-enhanced power Doppler was fully concordant with spiral CT findings in all of the posttreatment examinations. CONCLUSION: Considering the absence of false positive results in this study, echo-enhanced color power Doppler can be considered reliable in diagnosing incomplete necrosis of hepatocellular carcinomas after percutaenous ablation. Spiral computed tomography can thus be reserved for those cases in which the enhanced power Doppler examination reveals no evidence of vascularity.

Carcinoma, Hepatocellular↗

PubMed2005

Usefulness of contrast-enhanced transabdominal ultrasonography in the diagnosis of intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: The differentiation of benign from malignant intraductal papillary mucinous tumors (IPMT) is often difficult even by various examination methods. We evaluated the qualitative and quantitative diagnostic ability of contrast-enhanced transabdominal ultrasonography (CE-US), mainly in differentiating benign from malignant tumors in patients with IPMT. PATIENTS AND METHODS: There were 21 patients with IPMT who underwent CE-US and endoscopic ultrasonography (EUS). Surgery was performed in all 21 patients. Pathological findings were 4 with carcinoma and 17 with adenoma. CE-US was performed using a contrast agent (Levovist; Tanabe, Osaka, Japan) consisting of galactose microbubbles and a small (0.1%) admixture of palmitic acid, and the following items were evaluated by the following procedure. (1) Two reviewers with experienced sonographic and endosonographic ability evaluated CE-US images before and after contrast enhancement and classified the enhancement effects into three grades. In addition, the presence or absence of enhancement effects by CE-US was compared with that of mural nodules visualized by EUS. (2) In all 21 patients, changes in intensity after contrast enhancement were quantitatively measured using an HDI Lab. HDI Lab was provided by ATL (Philips; Bothell, WA) and these software tools rapidly quantify image characteristics within multiple ROI (regions of interest) and make comparisons between several areas or images. In both the early and late phases, the post-enhancement intensity, difference between pre- and post-enhancement intensity, and the percentage change ((post-enhancement value-pre-enhancement value)/pre-enhancement value) were compared between malignant and benign lesions, and the ability of CE-US to differentiate between benign and malignant lesions was evaluated in comparison with the ability of EUS to diagnose the degree of malignancy. RESULTS: (1) In both the early and the late phases, both reviewers observed enhancement effects in all 21 patients. And both reviewers observed mural nodules by EUS in all 21 patients. (2) In all 21 patients who underwent resection of IPMT, the intensity increased in both the early and late phases. When the patients with carcinoma were compared with those with adenoma, the post-enhancement intensity was significantly higher, and the difference between pre- and post-enhancement intensity and the percentage change in the early phase and the late phase was significantly more marked in the carcinoma group (p= 0.019, p= 0.002, p= 0.015, p= 0.012, and p= 0.039, respectively). CONCLUSIONS: CE-US was useful for qualitatively diagnosing tumor lesions in patients with IPMT. Moreover, quantitative changes in intensity can be a parameter for the differential diagnosis of benign and malignant tumors.

Abdomen↗

PubMed2005

Echographic examination with new generation contrast agent of choroidal malignant melanomas.

PURPOSE: To determine the efficacy of echography with new generation contrast agents in visualizing vascularization of choroidal malignant melanomas. METHODS: An echographic contrast medium consisting of phospholipidic microbubbles filled with sulphur hexafluoride (Sonovue) was used to visualize microcirculation in 25 cases of choroidal lesions already diagnosed with standardized echography (21 choroidal malignant melanomas, four disciform lesions). RESULTS: In untreated malignant melanomas contrast agent echography revealed the presence of a dense microcirculation inside the mass. In one case vitreal seeding of the contrast agent was detectable before enucleation and histological examination revealed the presence of tumoral cells. In 12 cases treated with transpupillary thermotherapy, contrast agent echographic evaluation showed heavy regression of microcirculation after 1 week, confirmed in one case by histology, and a reduction of 70-80% in dimensions after 6 months (which appeared to have stabilized at subsequent examinations). In four cases treated with proton beam brachytherapy 2 years prior to our examination, contrast agent echography showed the absence of a microvascular network and the presence of large vessels and blood lakes. In four cases of disciform lesion, deep and superficial retina-associated vascularization was observed, with a weak spread of contrast agent inside the lesion. CONCLUSION: Live representation with good resolution of choroidal malignant melanoma microcirculation was obtained.

Adult↗

PubMedDate not supplied

Ultrasonography of gastric ulceration in the dog.

The clinical, ultrasonographic and, when available, histopathologic findings of gastric ulceration in 7 dogs were reviewed. The most common clinical signs were vomiting, hematemesis, melena, weight loss and anemia. Ultrasonographic features of gastric ulcer included local thickening of the gastric wall, possible loss of the 5-layer structure, the presence of a wall defect or "crater," fluid accumulation in the stomach and diminished gastric motility. The localized gastric thickening varied from 9 to 16 mm. The ulcer crater was often located in the center of the thickened site and appeared as a mucosal defect associated with persistent accumulation of small echoes, most likely representing microbubbles. In this preliminary study, there was no definitive ultrasonographic distinction between benign and malignant ulcers.

Animals↗

PubMedDate not supplied

Quantitative evaluation of imagent as an abdominal ultrasound contrast medium in dogs.

Diagnostic ultrasound currently provides a noninvasive, economical means to evaluate internal organ structure. Methods to increase the amount of diagnostic information obtained from the sonographic examination are being explored. A new area of research has recently focused on the ability of microbubble contrast agents to help provide additional information. A prospective study was undertaken to quantitatively evaluate the amount of gray scale enhancement of ultrasound images of six canine livers, spleens, and left kidneys that occurs after intravenous injection of Imagent. Computerized analysis was used to assess the percent change in brightness of these images. A transient decrease in the percent change in brightness was seen to occur after injection of higher doses of Imagent. This effect was more pronounced in the deeper portions of the organs of interest. Imagent provides a measurable change in the brightness of the organs of interest and would be potentially useful in a clinical setting.

Abdomen↗

PubMedDate not supplied

Harmonic ultrasound: a review.

Harmonic ultrasound is a technique based on the principle of transmitting at frequency f and receiving at frequency 2f (or 1/2f). This technology has become available through the development of wide-bandwidth transducers. Microbubble contrast media produce a large amount of harmonic signal. Contrast harmonic ultrasound provides the opportunity to image patterns of high flow vasculature and overall perfusion. Regions of poor perfusion, including necrosis or infarction, can be identified with contrast harmonic ultrasound. While proportionately lower, tissues also produce harmonic signals. Tissue harmonic ultrasound sequences often improve subjective image quality compared to fundamental ultrasound in echocardiographic and abdominal examinations. This review will discuss the physical principles of harmonic ultrasound signal generation, medical and animal research applications, and an overview of current veterinary experiences.

Animal Diseases↗

PubMedDate not supplied

Quantitative contrast harmonic ultrasound imaging of normal canine liver.

Eight adult dogs with no evidence of liver disease, weighing between 8 and 25 kg were imaged after injection of a microbubble contrast medium using harmonic ultrasound imaging. All dogs received three separate bolus contrast injections, and six dogs also received three separate constant rate infusions each. Time/Mean Pixel Value curves were generated for selected regions of the liver. Upslope, downslope, baseline, peak, change, and time to peak were calculated. For bolus injection (averaging all subjects), upslope was 3.85 +/- 1.50 Mean Pixel Values/s, downslope was -0.71 +/- 0.30 Mean Pixel Values/s, baseline was 72.38 +/- 17.82 Mean Pixel Values, peak was 120.26 +/- 17.44 Mean Pixel Value, change from baseline to peak was 47.88 +/- 6.92 Mean Pixel Values, time to peak (from injection) was 22.88 +/- 6.79 s, and time to peak (from first upslope) was 13.88 +/- 1.55 s. Data acquisition and analysis from constant rate infusions was more cumbersome than for bolus, and results were less repeatable. There were significant differences (p < .005) in upslope, downslope, peak values, and time to peak between the two methods. These baseline data may prove useful in the evaluation of dogs with diffuse hepatic disease.

Animals↗

PubMedDate not supplied

Characterization of lymphomatous lymph nodes in dogs using contrast harmonic and Power Doppler ultrasound.

Doppler ultrasound has been used in humans to determine angioarchitecture of lymph nodes as the criterion for the determination of malignancy. We hypothesized that the vascular and perfusion patterns of a canine malignant lymph node could be characterized with intravenous microbubble ultrasound contrast media and that contrast harmonic ultrasound could provide better conspicuity of the angioarchitecture when compared with Power Doppler ultrasound. In this study, 11 peripheral lymph nodes in dogs with histologically verified malignant lymphoma were imaged with fundamental ultrasound, Power Doppler ultrasound, and three contrast harmonic pulse sequences to characterize the vascular pattern and perfusion. Vascular imaging was greatly enhanced in these nodes with 2.13 times more vessels seen with contrast harmonic ultrasound compared with Power Doppler ultrasound (P < 0.01). The angioarchitecture of lymphomatous lymph nodes of dogs in this study were similar to those previously described in malignant superficial lymph nodes in human patients; 45.5% of the nodes had displacement of the central hilar vessel, 45.5% had aberrant vessels, 63.6% had pericapsular vessels, 36.4% had subcapsular vessels, and 81.8% had loss of the central hyperechoic band in fundamental sonography. Poor perfusion, indicated by a lower mean pixel intensity increase between pre- and postcontrast administration images, was seen in 36.4% of the lymph nodes while 63.6% had fair to good perfusion. The perfusion patterns in nine of the 11 lymph nodes were homogenous and two showed focal hypoperfused regions. We conclude that Power Doppler and contrast harmonic ultrasound are beneficial in accurately depicting angioarchitechture and can provide additional information in determining the presence of malignant vascular characteristics within lymphomatous nodes in dogs.

Animals↗

PubMed2004

Emerging technologies in therapeutic ultrasound: thermal ablation to gene delivery.

Ultrasound is used today in medicine as a modality for diagnostic imaging. Recently, there have been numerous reports on the application of thermal and nonthermal ultrasound energy for treating various diseases. In addition to thermal ablation of tumors, non-thermal ultrasound combined with drugs and genes have led to much excitement especially for cancer treatment, vascular diseases, and regenerative medicine. Ultrasound energy can enhance the effects of thrombolytic agents such as urokinase for treatment of stroke and acute myocardial infarction. New ultrasound technologies have resulted in advanced devices such as a) ultrasound catheters, b) Non-invasive methods as high intensity focused ultrasound (HIFU) in conjunction with MRI and CT is already being applied in the clinical field, c) Chemical activation of drugs by ultrasound energy for treatment of tumors is another new field recently termed "Sonodynamic Therapy", and d) Combination of genes and microbubble have induced great hopes for ideal gene therapy (sonoporation). Various examples of ultrasound combined modalities are under investigation which could lead to revolutionary therapy.

Catheter Ablation↗

PubMed1999

Safety and ultrasound-enhancing potentials of a new sulfur hexafluoride-containing agent in the cerebral circulation.

Insufficient ultrasound penetration through the temporal bone is a serious limitation of transcranial ultrasound diagnostics. In a phase I study, the authors studied safety and ultrasound enhancing potentials of the new transpulmonary ultrasound contrast agent SonoVue, which contains sulfur hexafluoride gas microbubbles stabilized by a phospholipid shell. Twelve healthy volunteers received four different doses of SonoVue (0.3 ml, 0.6 ml, 1.2 ml, and 2.4 ml) intravenously. The duration of ultrasound contrast enhancement was measured by transcranial Doppler sonography (TCD) and transcranial color-coded sonography (TCCS). Safety and tolerability was monitored during the study and for 24 hours after contrast agent administration. TCD: Duration of spectral enhancement (signal intensity of 5 dB over baseline) was observed dose-related (p < 0.0001; Friedman-test) for (0.3 ml) 136 +/- 63.4 seconds; (0.6 ml) 191 +/- 63.3 seconds; (1.2 ml) 314 +/- 88 seconds; (2.4 ml) 434 +/- 168 seconds [mean +/- SD]. Dependent on dosage, the peak signal amplification in TCD was significantly different (p < 0.001; Friedman-test) as well: (0.3 ml) 24.5 +/- 2.0 dB; (0.6 ml) 26.0 +/- 1.6 dB; (1.2 ml) 27.6 +/- 2.2 dB; (2.4 ml) 28.4 +/- 2.2 dB (mean +/- SD). TCCS: Mean time of optimal enhancement increased from 214 +/- 73 seconds (0.3 ml) to 356 +/- 14 seconds (2.4 ml) in a dose-dependent manner. In TCCS, signal amplification appeared to be stronger with increasing doses. Adverse events were not observed during the study. This investigation describes the ultrasound enhancing potential of SonoVue in the intracranial cerebral circulation. SonoVue proved to be well tolerated and provided a long-lasting ultrasound contrast enhancement that supports an optimal transcranial ultrasound diagnostic.

Adult↗

PubMedDate not supplied

Measurement of the contrast agent intrinsic and native harmonic response with single transducer pulse waved ultrasound systems.

Ultrasound contrast agents, i.e., small gas filled microbubbles, enhance the echogenicity of blood and have the potential to be used for tissue perfusion assessment. The contrast agents scatter ultrasound in a nonlinear manner and thereby introduce harmonics in the ultrasound signal. This property is exploited in new ultrasound techniques like harmonic imaging, which aims to display only the contrast agent presence. Much attention has already been given to the physical properties of the contrast agent. The present study focuses on practical aspects of the measurement of the intrinsic harmonic response of ultrasound contrast agents with single transducer pulse waved ultrasound systems. Furthermore, the consequences of two other sources of harmonics are discussed. These sources are the nonlinear distortion of ultrasound in a medium generating native harmonics, and the emitted signal itself which might contain contaminating harmonics. It is demonstrated conceptually and by experiments that optimization of the contrast agent harmonic response measured with a single transducer is governed by the transducer spectral sensitivity distribution rather than the resonance properties of the contrast agent. Both native and contaminating harmonics may be of considerable strength and can be misinterpreted as intrinsic harmonics of the contrast agent. Practical difficulties to filter out the harmonic component selectively, without deteriorating the image, may cause misinterpretation of the fundamental as a harmonic.

Contrast Media↗

PubMed2003

High-frequency volume and boundary acoustic backscatter fluctuations in shallow water.

Volume and boundary acoustic backscatter envelope fluctuations are characterized from data collected by the Toroidal Volume Search Sonar (TVSS), a 68 kHz cylindrical array capable of 360 degrees multibeam imaging in the vertical plane perpendicular to its axis. The data are processed to form acoustic backscatter images of the seafloor, sea surface, and horizontal and vertical planes in the volume, which are used to attribute nonhomogeneous spatial distributions of zooplankton, fish, bubbles and bubble clouds, and multiple boundary interactions to the observed backscatter amplitude statistics. Three component Rayleigh mixture probability distribution functions (PDFs) provided the best fit to the empirical distribution functions of seafloor acoustic backscatter. Sea surface and near-surface volume acoustic backscatter PDFs are better described by Rayleigh mixture or log-normal distributions, with the high density portion of the distributions arising from boundary reverberation, and the tails arising from nonhomogeneously distributed scatterers such as bubbles, fish, and zooplankton. PDF fits to the volume and near-surface acoustic backscatter data are poor compared to PDF fits to the boundary backscatter, suggesting that these data may be better described by mixture distributions with component densities from different parametric families. For active sonar target detection, the results demonstrate that threshold detectors which assume Rayleigh distributed envelope fluctuations will experience significantly higher false alarm rates in shallow water environments which are influenced by near-surface microbubbles, aggregations of zooplankton and fish, and boundary reverberation.

Acoustics↗

PubMed2006

Acoustic response from adherent targeted contrast agents.

In ultrasonic molecular imaging, encapsulated micron-sized gas bubbles are tethered to a blood vessel wall by targeting ligands. A challenging problem is to detect the echoes from adherent microbubbles and distinguish them from echoes from nonadherent agents and tissue. Echoes from adherent contrast agents are observed to include a high amplitude at the fundamental frequency, and significantly different spectral shape compared with free agents (p <0.0003). Mechanisms for the observed acoustical difference and potential techniques to utilize these differences for molecular imaging are proposed.

Acoustics↗