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PubMed1995

Sonographic enhancement of renal cortex by contrast media.

The purpose of this study was to evaluate whether a phase shift contrast agent could enhance the renal cortex. Four doses of the contrast agent EchoGen ranging from 0.25 to 0.65 ml/kg were injected intravenously in three healthy dogs. Images of the kidney were recorded on a videotape before and after each injection. The images were evaluated visually and were computer-analyzed for brightness change caused by the contrast agent. Marked changes in cortical brightness were observed at the doses of 0.45 and 0.65 ml/kg. At lower doses the changes in image brightness were significantly reduced but measurable. The brightness peaked at 65 +/- 9 seconds after injection and gradually decreased to the baseline value in approximately 12 minutes. The video density varied nonlinearly with dose, and at low doses its value drifted below the baseline. This is believed to be due to attenuation of echoes by the contrast agent. The results of this study indicate that the microbubbles formed by phase shift contrast media are sufficiently small and persist long enough to enhance sonographic images of the cortex. Contrast media whose effect is based on the phenomenon of phase shift permit enhancement of the gray scale characteristic of the kidney. The enhancements last up to several minutes and have strong potential to allow investigation of perfusion in kidney.

Animals↗

PubMed1995

Parenchymal enhancement and tumor visualization using a new sonographic contrast agent.

The purpose of this study was to assess the ability of a sonographic contrast agent to increase parenchymal echogenicity and improve tumor visibility. The agent is an emulsion that changes at body temperature from nonechogenic submicrometer liquid droplets to echogenic 1 to 5 microns microbubbles, capable of transversing the pulmonary and capillary circulations. Peripheral venous injections (dosages of 0.05 to 0.8 ml/kg) were administered to five woodchucks (three with multiple hepatomas), 12 rabbits (with renal VX-2 tumors), and four dogs. Ultrasonograms were acquired from kidney, liver, tumors (including tumor vessels) and normal vessels. Uptake and washout curves were generated via videodensitometry. Finally, Doppler shifts from a cuff transducer around the celiac trunk were analyzed to provide an in vivo dose-response curve. Vascular enhancement, including hepatoma and VX-2 tumor vessels, was seen for 2 to 3 min. Maximum enhancement was 18.7 dB for a 0.6 ml/kg dose. Enhancement of normal liver and kidney parenchyma was observed in all three species for up to 20 min. Small hepatomas became more echogenic centrally, but larger tumors showed no increase in central echogenicity. In conclusion, improved tumor visibility and parenchymal enhancement was demonstrated in animals.

Animals↗

PubMed1995

Effect of pressure on echocardiographic videodensity from sonicated albumin: an in vitro model.

The effect of different pressures (0, 10, 30, 60, 80, 100, 120, or 180 mm Hg) on the ultrasound contrast effect obtained from sonicated albumin was evaluated by videodensity decay curves in an in vitro model immersed in a water tank. Decay rates and half-times were calculated from the videodensity decay curves at each pressure. A significant (P < 0.0001) relation was found between contrast disappearance and pressure: the higher the pressure the more rapid the contrast disappearance. Release of pressure did not result in contrast reappearance. Contrast decrease with pressure may result from microbubble destruction or alteration in acoustic properties by pressure. These findings may help explain the limited success of sonicated albumin for systemic ultrasonographic arteriography and myocardial perfusion imaging after intravenous injection. An ideal contrast agent for contrast echo studies should be stable at physiologic pressures.

Albumins↗

PubMed1996

On the feasibility of real-time, in vivo harmonic imaging with proteinaceous microspheres.

Harmonic imaging is a new contrast-specific imaging modality, which utilizes the nonlinear properties of microbubble-based sonographic contrast agents by transmitting at the fundamental frequency but receiving at the second harmonic frequency. The feasibility of improving the detection of slow, small-volume blood flow using real-time harmonic imaging has been investigated in vivo. Proteinaceous microspheres (FS069) were administrated to four dogs, two woodchucks (with multiple hepatomas), and one rabbit. Three different scanners were used to obtain real-time images of kidneys and liver (including vessels) in harmonic and conventional gray scale and color flow modes. The duration of contrast enhancement lasted significantly longer in harmonic than in conventional modes (on average 87 s; P = 0.008). Harmonic images were less susceptible to artifacts, such as acoustic shadowing, and a clear increase in the (flow) signal-to-noise ratio was observed. These preliminary in vivo results demonstrate the feasibility of performing real-time, contrast-enhanced harmonic imaging, but further studies are required to establish clinical efficacy.

Animals↗

PubMed1997

Mathematical modeling of the dilution curves for ultrasonographic contrast agents.

Most techniques using sonographic contrast agents are based on introducing the agent intravenously. The sonographic changes occur over time and follow a characteristic "skewed gaussian curve," often referred to as the indicator dilution curve. This study uses principles of linear acoustics and tracer kinetics to develop a quantitative model for the indicator dilution curve. A rapid increase in image brightness occurs after bolus injection; brightness peaks after a time related to the blood flow and stability of the contrast agent, which is followed by an asymptotic decrease in image brightness. The net image enhancement, represented by the area under the dilution curve, increases nonlinearly with the injected dose. In stable contrast agents the peak-time and mean transit time are related directly to the flow rate. This relationship changes when the microbubbles of a contrast agent collapse. In an unstable contrast agent the indicator dilution curve is attenuated and peaks earlier than expected on the basis of flow rate. The extent of shift in the mean transit time varies with the half-life of the contrast agent and follows a sigmoid relationship. In conclusion, the properties of the time-videointensity (indicator dilution) curves are significantly affected by the attenuation and stability of the contrast agents. These factors must be taken into consideration in deriving flow related information.

Absorption↗

PubMed1997

Contrast enhanced sonography of visceral perfusion defects in dogs.

The purpose of this study was to assess the utility of an intravenous contrast agent (FS069) for visualization of normal visceral perfusion compared with perfusion after segmental infarction in a canine model. Six mongrel dogs were used as subjects. Splenic, renal, hepatic, and small bowel perfusion was assessed without and with intravenous microbubble contrast material using gray scale, color Doppler, pulsed Doppler, and color power Doppler sonography. Each organ was then reassessed after ligation of a segmental vessel. Imaging was again performed without and with contrast material using all four ultrasonographic modalities. In all organs color and spectral Doppler signals were significantly enhanced from normally perfused tissue after intravenous contrast agent injection. Ischemic areas were more conspicuous after contrast medium injection except in the liver. Hepatic perfusion was maintained by portal flow in the liver despite arterial ligation. Ligation of collateral arcades was required to produce bowel ischemia. Intravenous injection of FS069 improves evaluation of visceral perfusion and identification of focal visceral ischemia in dogs. These results suggest that this agent may increase sensitivity for detection of blood flow in small and deep vessels.

Albumins↗

PubMed1999

Doppler sonographic enhancement of hepatic hemangiomas and hepatocellular carcinomas after perflenapent emulsion: preliminary study.

Ultrasonographic microbubble contrast agents improve Doppler signals by increasing blood backscatter. We retrospectively reviewed our experience with perflenapent (EchoGen), an emulsion of liquid dodecafluoropentane, in the evaluation of 13 patients with focal hepatic lesions (10 hemangiomas and six hepatocellular carcinomas). Perflenapent improved the detection of color Doppler flow signals within the lesions. The hemangiomas showed peripheral nonpulsatile signals and the hepatocellular carcinomas showed more diffuse enhancement with both arterial and venous type signals. This preliminary study suggests that perflenapent administration may aid in the sonographic differentiation of these focal lesions.

Adult↗

PubMed2000

Echo-enhanced color Doppler sonography in children and adolescents.

Fifty-one patients, with a range of underlying pathologic conditions, were studied prospectively to assess the diagnostic value of echo-enhanced color Doppler sonography in the pediatric and adolescent population Their diagnoses included various tumors, vascular disorders, cerebral bleeding, pathologic conditions of small parts, and focal lesions of parenchymal organs. All patients underwent color Doppler sonography before proceeding to echo-enhanced color Doppler sonography. Diagnoses were confirmed by additional imaging (computed tomography, magnetic resonance imaging, angiography, and scintigraphy) performed as appropriate, with or without histologic study. An additional 20 children did not proceed to echoenhanced color Doppler sonography as color Doppler sonography alone was found to be sufficiently diagnostic. Levovist (SHU 508A), a contrast agent based on galactose-encapsulated air microbubbles, is approved for pediatric applications in Austria and was used as the echo-enhancing agent. Echo-enhanced color Doppler sonography was performed a total of 63 times in 51 patients (mean age, 9.8 years). Compared to color Doppler sonography, echo-enhanced color Doppler sonography either detected or enhanced visualization of pathologic conditions in 55 investigations (87.3%), yielding an overall accuracy of 95.2% (sensitivity, 95%), versus 65.7% with color Doppler sonography. One spinal arteriovenous malformation, one cerebral cavernoma, and one liver lesion were missed. The contrast material was easy to administer; no adverse reactions were observed. We conclude that echoenhanced color Doppler sonography is beneficial in pediatric sonography. It enhances visualization of vessels and perfusion, thus offering a nonionizing imaging tool for detection and follow-up evaluation of pathologic conditions with disturbed vasculature in specific cases. In infants and in persons with superficial lesions it did not offer significant advantages over color Doppler sonography.

Adolescent↗

PubMed2000

Section 5--nonthermal bioeffects in the absence of well-defined gas bodies.

The purpose of this section is to describe bioeffects that occur in those instances in which gas bodies are not known to commonly be present. This is in contrast to situations such as lung and intestine, where bioeffects have been proposed to be associated with the known presence of gas (Section 4). In addition, this section does not include those studies in which microbubbles (such as ultrasound contrast agents) are purposefully introduced (Section 6). Therefore, this section includes a large collection of bioeffects that may be related to cavitation activity or may not be related at all to the presence of gas bodies. The intention is to provide an overall summary of the information currently available that pertains to those situations in which gas bodies are not known to be present and to provide this information in support of conclusions and recommendations on this subject.

Acoustics↗

PubMed2000

Section 6--mechanical bioeffects in the presence of gas-carrier ultrasound contrast agents. American Institute of Ultrasound in Medicine.

This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term "contrast agent" refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bioeffects associated with their presence in an ultrasonic field.

Acoustics↗

PubMed2000

Comparison of standard and second harmonic B-mode sonography in the detection of segmental renal infarction with sonographic contrast in a rabbit model.

This study compares contrast-enhanced fundamental and second harmonic B-mode sonography using a rabbit renal infarct model. Segmental renal infarctions were produced in 13 rabbits by embolizing a 0.7 mm bead into the renal artery 1 day prior to imaging. An ultrasonographic unit equipped with an L10-5 transducer and second harmonic imaging capability was used. Real-time recordings were made during the injection of 0.5 ml of an experimental formulation of a perfluorohexane vapor-stabilized microbubble (AF0145) given into the ear vein, and the imaging technique alternated between standard and harmonic imaging every 20 s. Each rabbit received two injections 1 h apart. To control for the effect of peak bolus enhancement, the initial imaging technique used for the first injection was randomized, and the other technique was used initially for the second injection. The videointensity difference between the infarcted and the normal cortex was then calculated and evaluated as a function of time. The infarcted segment could not be seen before administration of contrast agent with either technique. Although the infarction could be seen after injection of contrast agent with either technique, image contrast and contrast duration were nearly 75% greater for the harmonic technique than for the standard technique. AF0145 allows the visualization of segmental renal infarction on standard B-mode imaging. The second harmonic B-mode technique significantly increases image contrast and contrast duration.

Animals↗

PubMed2001

Flash echo gray scale imaging with subtraction in assessment of small hepatocellular carcinoma treated with percutaneous ethanol injection: preliminary report.

OBJECTIVE: To assess the therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma by using a flash echo imaging system, a newly developed technique for detecting echoes from microbubble contrast agents more efficiently. METHODS: Six patients with 7 small nodular hepatocellular carcinomas, proved by fine-needle aspiration cytologic or pathologic examination, were included. Percutaneous ethanol injection was performed until there was no intratumoral color signal on conventional color and power Doppler ultrasonography. A bubble contrast agent was then injected, and flash echo imaging in the subtraction mode was performed for assessment of the therapeutic effect. Dynamic computed tomography, magnetic resonance imaging, and hepatic angiography were also used for evaluation of the therapeutic effect. RESULTS: Five tumors had perfusion defects that were equal in size to or larger than the tumors. No tumor stain was shown on hepatic angiography. Two tumors had partial perfusion defects. Viable tumors were confirmed by tumor resection in 1 case and cytologic examination in the other. CONCLUSIONS: Our preliminary results show that flash echo imaging with subtraction has potential value in evaluation of the therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma.

Adult↗

PubMed2003

In vitro platelet activation by an echo contrast agent.

OBJECTIVE: We investigated whether an ultrasonic echo contrast agent containing microbubbles (Levovist [SH U 508A]; Schering AG, Berlin, Germany) could in routine use activate platelets. METHODS: Levovist and its main component, galactose, were mixed with separate samples of whole blood (1.5-75 mg/mL) from 5 healthy volunteers to form a 1-mL suspension sample. After in vitro exposure to ultrasound emitted from a commercial ultrasonic scanner at a pulse frequency of 3.5 MHz with a mechanical index of 1.9 and an exposure duration of 5 minutes, 5 microL of the sample was incubated for 20 minutes with the fluorescein isothiocyanate-labeled CD61 antibody, which is a platelet-specific antigen, and the phycoerythrin-labeled CD62P (P-selectin) antibody, an activation-specific antigen, both on the platelet surface. After more than 30 minutes of fixing in 1% paraformaldehyde, flow cytometric analysis was performed. RESULTS: The percentage of CD62P-expressing platelets increased according to the concentrations of Levovist and galactose, which showed almost equal effects. Ultrasound exposure did not enhance the effect except at the highest concentration of Levovist (75 mg/mL). CONCLUSIONS: In vitro, a galactose-based echo contrast agent could not activate the platelets at its routine concentration.

Adult↗

PubMed2003

Therapeutic response evaluation of malignant hepatic masses treated by interventional procedures with contrast-enhanced agent detection imaging.

OBJECTIVE: To assess the usefulness of microbubble contrast-enhanced agent detection imaging in evaluating the therapeutic response of malignant hepatic masses to treatment with interventional procedures. METHODS: Fifty-eight patients with 68 hepatocellular carcinomas and 6 metastases who were treated with interventional procedures were evaluated with SH U 508A-enhanced agent detection imaging and helical computed tomography. Helical computed tomography was also performed to help establish the outcome of therapy with unenhanced computed tomography 2 weeks after transcatheter arterial chemoembolization and with dynamic contrast-enhanced computed tomography 1 day after radio frequency ablation or percutaneous ethanol injection. The studies were reviewed separately and randomly, and the sensitivity and specificity of agent detection imaging for detection of viable tumor residue were determined by follow-up imaging performed at least 3 months later. RESULTS: Follow-up computed tomography or magnetic resonance imaging revealed complete tumor responses in 44 (59.5%) of 74 cases after the therapeutic procedures. The sensitivity of agent detection imaging was 94.7% after transcatheter arterial chemoembolization and 72.7% after radio frequency ablation and percutaneous ethanol injection. The specificity of agent detection imaging for the detection of residual tumors was 80% after transcatheter arterial chemoembolization and 79.2% after radio frequency ablation and percutaneous ethanol injection. The false-positive rate for agent detection imaging in cases of radio frequency ablation or percutaneous ethanol injection was 20.8% (5 of 24), resulting from reactive hyperemia or vascularity within the safety margin. In the assessment of the therapeutic effects, the concordance of contrast-enhanced agent detection imaging with helical computed tomography was statistically significant after transcatheter arterial chemoembolization (P < .00001) and radio frequency ablation or percutaneous ethanol injection (P < .02). CONCLUSIONS: Contrast-enhanced agent detection imaging proved useful and as effective as helical computed tomography for evaluating the therapeutic effects of interventional therapeutic procedures for malignant hepatic masses.

Adult↗

PubMed2004

Real-time imaging with the sonographic contrast agent SonoVue: differentiation between benign and malignant hepatic lesions.

OBJECTIVE: We investigated the ability of contrast-enhanced sonography with SonoVue (Altana Pharma, Konstanz, Germany), a sulfur hexafluoride microbubble contrast agent, to reveal differences between benign and malignant focal hepatic lesions. METHODS: One hundred twenty-six lesions in 124 patients with focal hepatic lesions detected by B-mode sonography (hepatocellular carcinoma, n = 36; metastasis, n = 25; cholangiocellular carcinoma, n = 1; lymphoma, n = 2; focal nodular hyperplasia, n = 9; adenoma, n = 4; regenerative cirrhotic nodule, n = 13; hemangioma, n = 29; and focal hyposteatosis, n = 7) were examined in a prospective study. After intravenous injection of 2.4 mL of SonoVue, the liver was examined continuously for 3 minutes by low-mechanical index pulse inversion sonography. RESULTS: For the discrimination of malignant versus benign liver lesions, SonoVue-enhanced sonography improved sensitivity from 78% to 100% and specificity from 23% to 92% compared with baseline sonography. Receiver operating characteristic analysis revealed a significant improvement in this discrimination (area under the receiver operating characteristic curve, 0.510 +/- 0.054 [SD] at baseline sonography, 0.998 +/- 0.003 with SonoVue-enhanced sonography; P < .001). The following flow patterns in the early phase were diagnosis specific: early central starlike pattern for focal nodular hyperplasia, peripheral globular-nodular pattern for hemangioma, and diffuse arterial enhancement for malignant lesions. Homogeneous enhancement in the late phase was predictive for benign lesions (P < .001). Conversely, 93% of patients without contrast enhancement in the late phase had malignant lesions (P < .001). CONCLUSIONS: SonoVue-enhanced sonography has greater specificity and sensitivity than baseline sonography for the differentiation of benign and malignant liver lesions.

Aged↗

PubMed2004

Evaluation of hepatic focal nodular hyperplasia with contrast-enhanced gray scale harmonic sonography: initial experience.

OBJECTIVE: To assess the potential of contrast-enhanced gray scale harmonic sonography in the evaluation of the typical vascular and enhancement patterns of hepatic focal nodular hyperplasia. METHODS: Thirteen patients with 13 lesions of hepatic focal nodular hyperplasia underwent contrast-enhanced gray scale harmonic sonography. After the injection of a microbubble contrast agent (SH U 508A), gray scale harmonic sonographic studies using a Coded Harmonic Angio technique were performed with a combination of a period of continuous scanning to assess the vascular pattern (vascular imaging) and interval delay scanning to determine the sequential enhancement pattern (acoustic emission imaging). Each imaging pattern was categorized and analyzed by consensus of 2 experienced radiologists. RESULTS: In 12 (92%) of 13 lesions, vascular imaging during the arterial phase showed central arteries of a spoked wheel pattern, whereas the remaining lesion had stippled vascularity. On acoustic emission imaging, 11 (85%) of 13 lesions were hyperechoic during the early phase, and the remaining 2 (15%) were isoechoic compared with surrounding parenchyma. Ten (77%) of 13 lesions remained either hyperechoic (5 of 13) or isoechoic (5 of 13) during the delay phase, whereas the remaining 3 lesions (23%) were hypoechoic. CONCLUSIONS: Contrast-enhanced gray scale harmonic sonography showed the typical vascularity of a spoked wheel pattern during the vascular phase and persistent enhancement on serial acoustic emission imaging in most cases of hepatic focal nodular hyperplasia, and thereby it can be a promising technique in noninvasive diagnosis of this entity.

Adolescent↗

PubMed2005

Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes.

OBJECTIVE: The purpose of this study was to determine whether lymphatic channels (LCs) and sentinel lymph nodes (SLNs) could be detected on sonographic imaging after subcutaneous, submucosal, or parenchymal injections of a sonographic contrast agent (ie, lymphosonography) in a variety of anatomic locations in several animal models. METHODS: Eight swine, 7 canines, 4 rabbits, and a monkey were used for these evaluations. Gray scale pulse inversion harmonic imaging of the LCs and the SLNs was performed after subcutaneous (n = 58), submucosal (n = 14), or parenchymal (n = 8) injections of a tissue-specific sonographic contrast agent (Sonazoid; GE Healthcare, Oslo, Norway). In many instances, blue dye was injected into the same locations as Sonazoid, and surgical dissection of the SLNs and LCs was performed for comparison. Scanning electron microscopy (SEM) of contrast-enhanced and control lymph nodes from 2 rabbits was performed to determine the mechanism of contrast agent uptake and retention within SLNs. RESULTS: After subcutaneous, submucosal, or parenchymal contrast agent injections, gray scale pulse inversion harmonic imaging could be used to identify the number and location(s) of LCs and SLNs. After subcutaneous, submucosal, or parenchymal contrast agent injections, Sonazoid was confined to the SLNs (ie, contrast enhancement was not detected in the second-echelon nodes). There was good agreement between the results of lymphosonography and blue dye with surgical dissection in identifying the regional LCs and SLNs. Scanning electron microscopy identified vacuoles representing intact contrast microbubbles within contrast-enhanced SLN macrophages, which were not present in the control lymph nodes. CONCLUSIONS: Lymphosonography can be used to detect lymphatic drainage pathways and SLNs in a variety of animal models.

Abdomen↗

PubMed2006

Relationship of skeletal muscle perfusion measured by contrast-enhanced ultrasonography to histologic microvascular density.

OBJECTIVE: The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. METHODS: Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. RESULTS: Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). CONCLUSIONS: B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.

Adult↗