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PubMed1999

Contrast-enhanced three-dimensional power Doppler angiography of the human prostate: correlation with biopsy outcome.

OBJECTIVES: To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome. METHODS: 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system. RESULTS: Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant. CONCLUSIONS: Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Angiography↗

PubMed1986

Coronary artery surgery with patient's lungs as oxygenator.

The use of the patient's own lungs as oxygenator was assessed during coronary artery bypass grafting in 20 patients. This technique maintained the circulation and provides excellent oxygenation, and the lungs did not intrude on the operative field. Blood damage as assessed by platelet function and lung sequestration was less than that reported with other forms of bypass. No microbubbles were produced, since there was no artificial blood/air interface. Complement activation, as assessed by amount of white-cell sequestration in the lungs, was also lower than that reported in other forms of bypass. There were no major complications attributable to the technique. Apart from being substantially cheaper than conventional cardiopulmonary bypass, the use of the patient's lungs as oxygenator offers the potential advantage of reduced trauma to the blood and merits further consideration.

Adult↗

PubMed1999

Colloidal gas aphrons: potential applications in biotechnology

Colloidal gas aphrons are microbubbles encapsulated by surfactant multilayers. They provide a large interfacial area to adsorb charged and/or hydrophobic molecules; the extent and mechanism of the adsorption depends on the surfactant multilayer. The physical properties of colloidal gas aphrons have recently been characterized for a range of surfactants in order to find the best systems for particular applications. A range of exciting biotechnology applications has been identified, including the recovery of cells, proteins and other biological molecules, and the enhancement of gas transfer in bioreactors and bioremediation.

Journal Article↗

PubMed1997

Changes in blood supply in small hepatocellular carcinoma: correlation of angiographic images and immunohistochemical findings.

BACKGROUND/AIMS: To assess the changes occurring in blood flow with growth in small hepatocellular carcinomas, we analyzed the angiographic features and immunohistochemical findings in 35 hepatocellular carcinomas less than 2 cm in diameter. METHODS: Hepatocellular carcinomas were evaluated by digital subtraction angiography (DSA), ultrasound angiography with intraarterial CO2 microbubbles (USAG), and computed tomography during arterial portography (CTAP). Immunohistochemically, hepatocellular carcinomas were evaluated using QB-end/10 (QB) monoclonal antibody. RESULTS: All 18 moderately-differentiated hepatocellular carcinomas stained positively with QB antibody. No hepatocellular carcinomas without attenuation on CTAP were positive by immunohistochemistry, and two hepatocellular carcinomas with attenuation on CTAP also lacked staining. We observed four hepatocellular carcinomas without hypervascularity on DSA or USAG, which stained positively with QB antibody; these hepatocellular carcinomas had fatty metamorphosis. CONCLUSIONS: 1. Immunohistochemical findings are closely associated with angiographic findings regarding changes in blood supply. 2. All moderately-differentiated hepatocellular carcinomas have characteristics of hypervascularity, both by angiographic images and by immunohistochemistry. 3. The increase in arterial blood supply occurs later than the decrease in portal perfusion, which may indicate that the decrease in portal perfusion may not be the direct result of replacement by angiogenesis. 4. Some hepatocellular carcinomas with fatty metamorphosis, which are often hypovascular by angiographic evaluation, have hypervascular immunohistochemical characteristics.

Aged↗

PubMed1997

Significance of tumor vascularity as a predictor of long-term prognosis in patients with small hepatocellular carcinoma treated by percutaneous ethanol injection therapy.

BACKGROUND/AIMS: We estimated the significance of the vascularity of small hepatocellular carcinoma (HCC) as a predictor of long-term prognosis in patients treated with percutaneous ethanol injection therapy (PEIT/PEI). METHODS: Fifty-four patients who have been followed-up in our hospital and who had HCC less than 20 mm in diameter were observed for 199 to 2074 days. Hepatic angiography (digital subtraction angiography; DSA and ultrasound angiography with intraarterial CO2 microbubbles; USAG) was performed before treatment in all cases, and the vascularity of the tumor was clinically evaluated. The survival rate was analyzed according to this vascularity. RESULTS: Of the 54 tumors, 24 had tumor stain on DSA, while 30 did not, and 38 showed enhancement on USAG, while 16 did not. The 3- and 5-year survival rates were 48.7 and 34.1% and 89.7 and 69.7% of patients with negative staining HCC (p = 0.0723). The rates were 48.6 and 36.7%, respectively, of patients with positive enhancement HCC on USAG, and both rates were 85.7% of patients with negative enhancement HCC (p = 0.0231). CONCLUSIONS: Tumor vascularity will play a role in the long-term prognosis of these patients with small HCC when they are treated with PEIT/PEI.

Administration, Cutaneous↗

PubMed1999

Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis.

BACKGROUND/AIMS: Blood concentration levels of alpha-fetoprotein like the Lens culinaris agglutinin-reactive fraction (AFP-L3) are a useful marker for predicting the long-term prognosis of hepatocellular carcinoma. This study investigated the relationship between serum AFP-L3 and various imaging modalities. METHODS: Sixty-three patients with small hepatocellular carcinomas < or = 2 cm in diameter were studied. Serum AFP-L3 concentrations were measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting and expressed as % AFP-L3 (the percent of AFP-L3 as total AFP). A clinical "cutoff level" of 10% was used in this study to indicate the presence of hepatocellular carcinoma. Selective hepatic intraarterial digital subtraction angiography (DSA), ultrasonographic angiography with carbon dioxide microbubbles (USAG), and computed tomography during arterial portography (CTAP) were performed to evaluate the hemodynamics of hepatic nodules. RESULTS: Fourteen (22.2%) of the 63 patients were positive for % AFP-L3. The % AFP-L3 levels (n=45, 4.4%) of patients with hypervascular tumors were significantly higher than those (n=15, 0.0%) of patients with isovascular or hypovascular tumors as determined by USAG (p=0.0061). The % AFP-L3 levels (n=53, 4.4%) of patients with a negative portal blood supply were significantly higher than the % AFP-L3 levels (n=7, 0.0%) of patients with a positive portal blood supply as determined by CTAP (p=0.0140). The % AFP-L3 levels of patients with tumors with a long doubling time (DT) were significantly lower than for patients with tumors with a short DT (p=0.0176). CONCLUSION: AFP-L3 is a positive indicator which may be more specific for small advanced hepatocellular carcinoma.

Aged↗

PubMed2006

[Transrectal ultrasound and biopsy of the prostate].

This review describes the transrectal ultrasound (TRUS) features of prostate cancer (PC), discusses the role of TRUS in the detection of PC and defines the modalities of biopsies in patients with suspected PC, particularly concerning prevention of complications, the number of biopsies and the biopsy schemes ensuring an optimal cancer detection rate. TRUS alone has limited potential to identify PC because of frequent multifocality of cancer within the prostate, the variable sonographic appearance of prostatic tumors, the poor specificity of focal US abnormalities, and the substantial percentage of isoechoic PC. Over the past decade, the sextant biopsy technique has emerged as the standard of care in the detection of PC. However, limitations in cancer detection have been appreciated, particularly a false-negative rate approaching 20%. This high failure rate has led investigators to refine biopsy techniques to improve cancer detection and to increase the total number of cores. Currently, recommendations include increasing the biopsy number to a minimum of 10-12 cores, including sampling of the lateral prostate. Refinements in imaging technologies (power Doppler sonography, microbubble intravenous sonographic contrast agents, and MR spectroscopy or dynamic contrast MR imaging) should eventually improve targeting of prostate needle biopsy and reduce false-negative biopsies.

Biopsy↗

PubMedDate not supplied

Highly fluorinated amphiphiles and colloidal systems, and their applications in the biomedical field. A contribution.

Fluorocarbons and fluorocarbon moieties are uniquely characterized by very strong intramolecular bonds and very weak intermolecular interactions. This results in a combination of exceptional thermal, chemical and biological inertness, low surface tension, high fluidity, excellent spreading characteristics, low solubility in water, and high gas dissolving capacities, which are the basis for innovative applications in the biomedical field. Perfluoroalkyl chains are larger and more rigid than their hydrogenated counterparts. They are considerably more hydrophobic, and are lipophobic as well. A large variety of well-defined, modular fluorinated surfactants whose polar head groups consist of polyols, sugars, sugar phosphates, amino acids, amine oxides, phosphocholine, phosphatidylcholine, etc, has recently been synthesized. Fluorinated surfactants are significantly more surface active than their hydrocarbon counterparts, both in terms of effectiveness and of efficiency. Despite this, they are less hemolytic and less detergent. Fluorosurfactants appear unable to extract membrane proteins. Fluorinated chains confer to surfactants a powerful driving force for collecting and organizing at interfaces. As compared to non-fluorinated analogs, fluorosurfactants have also a much stronger capacity to self-aggregate into discrete molecular assemblies when dispersed in water and other solvents. Even very short, single-chain fluorinated amphiphiles can form highly stable, heat-sterilizable vesicles, without the need for supplementary associative interactions. Sturdy microtubules were obtained from non-chiral, non-hydrogen bonding single-chain fluorosurfactants. Fluorinated amphiphiles can be used to engineer a variety of colloidal systems and manipulate their morphology, structure and properties. Stable fluorinated films, membranes and vesicles can also be prepared from combinations of standard surfactants with fluorocarbon/hydrocarbon diblock molecules. In bilayer membranes made from fluorinated amphiphiles the fluorinated tails segregate to form an internal teflon-like hydrophobic and lipophobic film that increases the stability of the membrane and reduces its permeability. This fluorinated film can also influence the behavior of fluorinated vesicles in a biological milieu. For example, it can affect the in vivo recognition and fate of particles, or the enzymatic hydrolysis of phospholipid components. Major applications of fluorocarbons currently in advanced clinical trials include injectable emulsions for delivering oxygen to tissues at risk of hypoxia; a neat fluorocarbon for treatment of acute respiratory failure by liquid ventilation; and gaseous fluorocarbon-stabilized microbubbles for use as contrast agents for ultrasound imaging. Fluorosurfactants also allow the preparation of a range of stable direct and reverse emulsions, microemulsions, multiple emulsions, and gels, some of which may include fluorocarbon and hydrocarbon and aqueous phases simultaneously. Highly fluorinated systems have potential for the delivery of drugs, prodrugs, vaccines, genes, markers, contrast agents and other materials.

Animals↗

PubMed2000

Improved imaging of hepatic metastases with delayed pulse inversion harmonic imaging using a contrast agent SH U 508A: preliminary study.

To investigate the feasibility of delayed pulse-inversion harmonic imaging (PIHI) with the SH U 508A to improve imaging of hepatic metastases, we evaluated 20 patients with known hepatic metastases. Conventional ultrasound (US) was performed before administration, and PIHI was performed 5 min after a bolus injection of 4 G of microbubble contrast agent (300 mg/mL of SH U 508A). Intense, homogeneous enhancement in the liver parenchyma was seen in all patients on delayed PIHI. In 10 patients (50%), 1 or more focal liver lesions that were not seen on unenhanced imaging were detected on delayed PIHI. When comparing 55 lesions that were seen on both techniques, delayed PIHI was superior to unenhanced imaging in terms of lesion conspicuity and lesion-to-liver contrast (p < 0.001, respectively). Delayed PIHI with SH U 508A can improve conspicuity of hepatic metastases and reveal focal liver lesions that are not detected on unenhanced imaging.

Adult↗

PubMed2001

Fibroadenomas: computer-assisted quantitative evaluation of contrast-enhanced power Doppler features and correlation with histopathology.

We aimed to evaluate whether the histopathologic variability of fibroadenomas accounts for their varied appearance in contrast enhanced power Doppler (PD). Forty patients with fibroadenomas (aged 19 to 61 years) underwent power Doppler ultrasound (US) prior to and following IV bolus injection of a microbubble contrast agent. A 3-min computer-assisted assessment of the color pixel density (CPD) was used for objective evaluation of the increase in color Doppler signals. Enhancement characteristics were correlated to histopathologic features of microvessel density and epithelial hyperplasia, patient's age, tumor size, use of exogenous hormones and menopausal status. Epithelial hyperplasia was diagnosed in 19 patients. Compared to baseline values, patients with epithelial hyperplasia showed a significant increase in mean CPD following contrast media administration (p < 0.01). There was a significant correlation to patient's age (p < 0.0001) and tumor size (p < 0.0001), but not to the use of exogenous hormones and menopausal status. Microvessel counts did not show a significant correlation to CPD at baseline (p = 0.07) or with CPD on contrast enhanced PD (p = 0.13), or with patient age (p = 0.43) or tumor size (p = 0.34). Intratumoral epithelial hyperplasia, primarily occurring in young patients, may contribute to the differential diagnostic overlap in some fibroadenomas and thus limit the ability of PD to distinguish between benign and malignant masses on the basis of enhancement characteristics.

Adult↗

PubMed2002

Contrast-enhanced power Doppler sonography: assessment of revascularization flow in Legg-Calvé-Perthes' disease.

A total of 26 children (26 affected, 25 control hips) with Legg-Calvé-Perthes' disease (LCP) met the cooperation requirements for inclusion in the study using contrast-enhanced power Doppler sonography for assessment of changes in the revascularization flow. Sagittal sonograms were obtained before and at the peak effect of an intravenously injected microbubble-based contrast agent. Overall mean peak enhancement ratios were greater for children with later onset of disease (>5.8 years old) than for those with earlier onset (< or = 5.8) (p = 0.02). The use of ultrasound (US) contrast agents improved depiction of proximal femoral vascularity in all regions of the femoral head: epiphysis (n = 3, pre; n = 8, postcontrast), physis (n = 12, pre; n = 21, postcontrast) and metaphysis (n = 6, pre; n = 8, postcontrast) and resulted in a marked increase in the number of mean pixel intensity values within the physis (p = 0.02). In conclusion, contrast-enhanced power Doppler sonography is an effective method for demonstration of changes from the revascularization process in LCP, particularly within the physis.

Child↗

PubMed2002

Improved sonographic imaging of hepatic hemangioma with contrast-enhanced coded harmonic angiography: comparison with MR imaging.

The aim of this study was to compare peripheral nodular enhancement with centripetal progression on contrast-enhanced coded harmonic angio (CHA) with those as seen on magnetic resonance imaging (MRI) scan. A total of 20 patients with 24 hemangiomas confirmed by dynamic contrast-enhanced MRI were included in this study. All 20 patients were examined with CHA in conjunction with a galactose-based microbubble contrast agent (SH U 508A) and with interval delay scanning. The pattern and the time of contrast enhancement were recorded on CHA images. We compared CHA images with MRI in terms of the similarity of contrast-enhanced peripheral nodules. The significance of size of tumor and baseline echogenicity on the ability to see peripheral nodular enhancement was independently assessed. Peripheral nodular enhancement was shown on CHA in 22 (92%) of 24 hemangiomas. Of 22 hemangiomas, 21 (95%) with peripheral nodular enhancement had progressive centripetal fill-in on CHA images. In 4 (80%) of 5 hemangiomas less than 1.5 cm in diameter, contrast-enhanced peripheral nodules were depicted on CHA images. In terms of the similarity of peripheral nodules, CHA images showed the similarity more than "similar" grade with MRI in 21 (95%) of 22 hemangiomas. This study shows that CHA is approximately equal to MRI in its ability to show peripheral nodular enhancement with centripetal progression, even in small hemangiomas.

Adult↗

PubMed2002

Optimal pulse-inversion imaging for microsphere contrast agents.

Microbubbles are used as contrast agents because they scatter incident ultrasound (US) efficiently. Pulse-inversion imaging makes use of the asymmetrical difference in response of a bubble to an US pulse and its symmetrical opposite to obtain improved contrast. In this theoretical work, the principle of pulse-inversion imaging is expanded upon by finding the optimal pulse shape to maximize the signal from a bubble. Given a limit on driving intensity, a suitable norm of the bubble response is maximized using optimal control theory to identify the proper pulse/antipulse driving protocol for a single bubble. The optimal pulse yields a several-fold increase in the normed response over the best sinusoidal pulse of the same driving intensity. It was found that the optimal driving for a single bubble also maximizes the nonlinear response of the cloud if its mean bubble size is the same as that of the single bubble.

Biomedical Enhancement↗

PubMed2002

Potential of gold-bound microtubules as a new ultrasound contrast agent.

Contrast agents based on gas-filled microspheres share the problem of time limited opacification due to low stability of microbubbles. The aim of this study was to test if gold-bound microtubules provide backscattering that allows microtubules to be potentially useful as an ultrasound (US) contrast agent. Gold colloids were immobilized on protein microtubule walls. Latex balloons were filled with gold-bound microtubules or conventional left heart contrast agent and were ultrasonographically imaged in fundamental and harmonic modes. Feasibility of anti-beta-tubulin antibody conjugation to gold-bound microtubules was confirmed using immune fluorescence analysis. Gold particles were successfully bound to microtubules. Contrast intensities in latex balloons filled with gold-bound microtubules (141 +/- 35) were comparable to those with Levovist (180 +/- 35) and did not decrease significantly during continuous US imaging for 20 min (135 +/- 34 vs. Levovist 5.0 +/- 2.0). Anti-beta-tubulin antibodies were successfully conjugated to gold-bound microtubules. Gold-bound microtubules provide a persistent contrast effect, suggesting their use as an ultrasonic contrast agent with the feasibility of antibody conjugation.

Animals↗

PubMed2002

Pressure-dependent attenuation in ultrasound contrast agents.

Although microbubble contrast agents are believed to respond differently under different driving-pressure amplitudes, few studies have been performed to extensively study the pressure-dependence of their properties. In this paper, attenuation coefficients of two contrast agents (Optison and Definity) were measured under different driving-pressure amplitudes using a narrowband incident pulse. The attenuation of both contrast agents was found to increase with increasing driving pressure. Simulations using the Rayleigh, Plesset, Noltingk, Neppiras, Poritsky (RPNNP) equation were performed to study this behavior. Simulation results show that significant harmonic generation at high driving-pressure amplitudes contributes to the higher attenuation. Other possible explanations for this behavior were also examined. Attenuation coefficients of two contrast agents were also measured using a broadband method. The results showed great inconsistency when the center frequency of the incident broadband pulse was changed, indicating that broadband techniques may not be suitable for contrast-agent attenuation measurements.

Albumins↗

PubMed2002

Spontaneous homogeneous nucleation, inertial cavitation and the safety of diagnostic ultrasound.

Gas bubbles of sufficient size to serve as cavitation nuclei may form spontaneously in tissue in regions of very low interfacial tension. In the absence of an acoustic wave or other mechanical stress, such nuclei will quickly dissolve and disappear from the medium. Under the influence of an acoustic wave, however, these microbubbles may grow to many times their initial size and then collapse violently, a process known as inertial cavitation. In this work, the in vivo energetics and dynamics of the nucleation-cavitation process were modeled by treating tissue as a homogeneous fluid. The assumption of a viscosity of 10(-3) Pa s (i.e., that of water) resulted in the lowest acoustic rarefactional pressure threshold for nucleation-cavitation events, approximately 4.0 MPa, which was essentially frequency-independent over the range 1 to 15 MHz. The rarefactional pressure threshold for a viscosity of 5 x 10(-3) Pa s (that of blood) also was approximately 4.0 MPa at 1 MHz, but the threshold for this higher viscosity increased nearly linearly with frequency above approximately 5 MHz, never being more than approximately 0.2 MPa below the equivalent derated peak rarefactional pressure calculated assuming MI = 1.9, the current USFDA guideline.

Biomechanical Phenomena↗

PubMed2003

Contrast-specific ultrasonic flow measurements based on both input and output time intensities.

Ultrasonic contrast agents are used to assess perfusion conditions based on evaluation of the time-intensity curve. Such a curve reflects the concentration of microbubbles in the perfused area and the indicator-dilution theory is used to derive the volumetric flow rate from the measured concentration. Previous results have shown that the technique is not reliable in some conditions due to the shadowing effect. To overcome this problem, a contrast-specific technique using both the input and output time-intensity relationships is proposed; this contrasts with conventional techniques that utilize only the relationship directly from the perfused area. The proposed technique is referred to as the input-output time-intensity curve (IOTIC) method. In this work, the shadowing effect was studied experimentally and the efficacy of the IOTIC technique was assessed and compared with conventional techniques. The results indicate that the IOTIC technique eliminates the shadowing effect and provides a good correlation between the actual flow rate and measured flow-related parameters; thus, making quantitative estimation of perfusion feasible. Note that the IOTIC is applicable, based on the assumption that both the input and the output can be positioned within the same image plane; its clinical applications include situations where the perfused area cannot be effectively imaged by ultrasound (US). One example is the assessment of brain perfusion, and it will be used as a target clinical application of the IOTIC technique.

Cerebrovascular Circulation↗

PubMed2003

Effect of Levovist on splanchnic hemodynamics in cirrhotic patients.

This study was aimed to assess the effect of Levovist on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 +/- 0.07 vs. 0.71 +/- 0.06; p < 0.01) and splenic arteries (0.72 +/- 0.06 vs. 0.64 +/- 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase.

Aged↗