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PubMed2006

Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue: initial experience.

OBJECTIVE: The purpose of this study was to investigate the imaging findings of peripheral cholangiocarcinoma with low-mechanical index (MI) contrast-enhanced sonography. METHODS: Eighteen nodules of peripheral cholangiocarcinoma proved by pathologic examination in 18 patients were evaluated with contrast-enhanced sonography. A low-MI real-time contrast-enhanced sonographic mode (ie, contrast pulse sequencing) and a sulfur hexafluoride-filled microbubble contrast agent (SonoVue [BR1]; Bracco SpA, Milan, Italy) were used. RESULTS: On contrast-enhanced sonographic images, all 18 nodules (100%) of peripheral cholangiocarcinoma showed inhomogeneous enhancement during the arterial phase, and the emergence of nodule enhancement was earlier in 3 nodules (16.7%), simultaneous in 13 (72.2%), and later in 2 (11.1%), respectively, when compared with the adjacent liver tissue. During the arterial phase, 8 nodules (44.4%) showed irregular peripheral rimlike hyperenhancement, 2 (11.1%) showed inhomogeneous hyperenhancement, and 8 (44.4%) showed inhomogeneous hypoenhancement. In portal and late phases, all 18 nodules (100%) showed hypoenhancement. When contrast-enhanced sonography was added for analysis, the confidence levels of the investigators were improved in 15 (83.3%) of 18 nodules, and 17 (94.4%) of 18 peripheral cholangiocarcinomas were correctly characterized. CONCLUSIONS: The imaging findings of peripheral cholangiocarcinoma had some characteristics on low-MI contrast-enhanced sonography. Knowledge of these characteristics might be beneficial for improving the diagnostic performance of sonography in evaluating this entity.

Adult↗

PubMed2006

Characterization of small focal liver lesions using real-time contrast-enhanced sonography: diagnostic performance analysis in 200 patients.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of real-time contrast-enhanced sonography in characterization of small focal liver lesions (FLLs; < or = 3.0 cm in diameter). METHODS: Two hundred small FLLs in 200 patients were examined by contrast-enhanced sonography using a contrast-specific mode of contrast pulse sequencing and a sulfur hexafluoride-filled microbubble contrast agent. The sonographic images were reviewed by 2 independent readers. A 5-point confidence level was used to discriminate malignant from benign FLLs, and specific diagnoses were recorded. The diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis, and the interobserver agreement was analyzed by weighted kappa statistics. RESULTS: After review of contrast-enhanced sonography, ROC analysis revealed significant improvement in differentiating between malignant and benign small FLLs that the areas under the ROC curve were 0.856 at baseline sonography versus 0.954 at contrast-enhanced sonography for reader 1 (P < .001) and 0.857 versus 0.954 for reader 2 (P = .003). The sensitivity, negative predictive value, and accuracy for both readers also improved significantly after contrast agent administration (all P < .001). A better result of specific diagnosis was obtained (38.5% [77/200] at baseline sonography versus 80.5% [161/200] at contrast-enhanced sonography for reader 1 and 34.5% [69/200] versus 80.5% [161/200] for reader 2; both P < .001) after contrast agent administration, and a better interobserver agreement was achieved (kappa = 0.425 at baseline sonography versus 0.716 at contrast-enhanced sonography). CONCLUSIONS: Real-time contrast-enhanced sonography improves the diagnostic performance in small FLLs compared with baseline sonography.

Adult↗

PubMed2004

Acoustic signatures of submicron contrast agents.

Previous studies have revealed that hard-shelled submicron contrast agents exhibit large relative expansions and strong acoustical echoes that can be observed experimentally, and predicted by theoretical simulations. In this paper, we study harmonic imaging and pulse-pair imaging techniques designed to assist in the differentiation of these contrast agents from tissue. For harmonic imaging, we apply a high-sensitivity, narrowband strategy that differentiates the microbubble from tissue based on the generation of strong harmonic echoes. For pulse-pair imaging, we apply high spatial resolution, wideband strategies using phase inversion, which relies on the frequency differences observed in response to phase-inverted pulses, and signal subtraction, which takes advantage of the amplitude differences in response to identical pulses. The bubble-to-phantom signal amplitude ratio in the absence of motion approaches 20 dB using phase inversion and 30 dB using signal subtraction; both techniques are robust for up to 50 microm of simulated motion. With the experience gained in these studies, we hope to advance the development of multi-pulse or shaped-pulse techniques that are optimized for specific clinical applications.

Connective Tissue↗

PubMed2004

Contrast-agent detection and quantification.

The Cadence contrast pulse sequencing (CPS) technology offers improved clinical information and workflow efficiency during contrast agent examinations. The technology harnesses unique non-linear microbubble energy discovered within the same fundamental frequency band as the transmitted pulses of sound and thus offers improved sensitivity and penetration. An auto tracking contrast quantification (ACQ) technology further complements the CPS detection technology with automatic image alignment during quantification with features such as on-line multiple time intensity curves (TIC). The regional image analysis holds promise of alleviating workflow inefficiency associated with manual alignment of image frames.

Contrast Media↗

PubMed2004

Contrast-enhanced ultrasound of the kidneys.

The development of ultrasound contrast agents and dedicated software for the detection of microbubbles has improved the potential contrast resolution of ultrasound and this, added to the already excellent spatial and temporal resolution, makes contrast-enhanced ultrasound (CEUS) well suited for the study of many organs, not only the liver. The contrast agents in clinical use today are so called blood pool agents meaning that, contrary to X-ray contrast media, they do not leave the blood vessels. This provides us with an excellent tool for delineating tissues with perfusion differences and for following the dynamic phases of contrast enhancement, in both large vessels and the microcirculation in parenchymatous organs. For vascular applications, CEUS improves detection of the renal arteries as well as strengthening Doppler signals. Emboli, posttraumatic rupture and other conditions impairing perfusion are readily detected and it may be possible to estimate blood flow by quantifying the contrast enhancement. The CEUS changes in diffuse renal disease are little explored but regional perfusion differences, such as in pyelonephritis, may be seen and quantified. In focal lesions, CEUS helps in the evaluation of atypical cysts and indeterminate masses detected on CT or MR. Many solid lesions may have a perfusion similar to the renal parenchyma but since many tumours are hypovascular, they tend to become echopoor relative to the enhanced renal parenchyma. The detection of a necrotic centre may further help both detection and characterization.

Contrast Media↗

PubMed2004

[Perfusion imaging of the kidney using contrast-enhanced phase-inversion ultrasound].

PURPOSE: We evaluated different techniques of contrast-enhanced phase-inversion ultrasound to visualize renal perfusion. MATERIALS AND METHODS: Levovist contrast-enhanced phase-inversion ultrasound with different levels of mechanical index and frame rate was performed in 20 kidneys. Analysis using a software algorithm for time-resolved perfusion imaging was compared to single-image analysis performed by three independent radiologists. RESULTS: Optimal depiction of renal perfusion was achieved only by using a mechanical index which was high enough to destroy the microbubbles of the contrast agent (burst imaging) combined with a low frame rate (0.5 images/second). Renal cortex and medulla showed a homogeneous enhancement. Computer-assisted time-resolved perfusion analysis was applicable; it did not show additional Information to single-image analysis. CONCLUSION: Renal perfusion can be visualized using contrast-enhanced phase-inversion ultrasound. For depiction of bigger vessels, it is equal to B-mode ultrasound or Doppler mode techniques; however, it is superior for visualization of renal parenchymal perfusion.

Adult↗

PubMed2005

[Experimental study of the characteristics of renal blood flow with contrast ultrasound].

OBJECTIVE: To study the characteristics of renal blood flow with contrast ultrasound. METHODS: The examination of the renal ultrasonography was performed in 10 dogs after intravenous injection of Quanfuxian (a contrast agent consisting of C3F8 microbubbles). RESULTS: Contrast visualization appeared in the renal cortex and then in the outer to inner medulla at the baseline level after administration of the contrast agent. Notable differences in the values of microvascular volume (A, which was 120.3 in the corted vs 110.8 in the medulla, P>0.05), microcirculatory flow velocity (beta, which was 1.39 in the corted vs 0.54 in the medulla, P<0.05), and microcirculatory flow rate (A x beta, 167.4 in the corted vs 59.5 in the medulla, P<0.05) were found between the corted and the medulla, with also marked difference between the the corted-to-the medulla ratios of beta and A (0.612 vs 0.078, P<0.05). CONCLUSION: Contrast ultrasound of the kidney provides a useful means of renal circulatory flow study.

Animals↗

PubMed2005

[Design of a quantitative analysis software system for myocardial contrast echocardiography].

This article reports a quantitative analysis software system for myocardial contrast echocardiography (MCE). It can measure the signal intensity of grayscale images and power Doppler images, draw the time-intensity curves of variations on the intensity of microbubbles scattering in subendocardial layer and subepicardial layer with the pulsing intervals, and estimate the hemodynamic parameters by nonlinear regression analysis. This system has been applied to a study on 20 healthy volunteers, and the results suggest that the software has the capacity for bringing the quantitative analysis of MCE to success. The MCE software system conforms to the DICOM standard and can be integrated into PACS.

Adult↗

PubMed2006

Cellular and molecular imaging with targeted contrast ultrasound.

There is growing interest in the availability of methods for imaging disease at the level of the cellular and/or molecular mediators. Techniques for imaging molecular alterations have been develop for essentially all non-invasive cardiac imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on the detection of novel site-targeted contrast agents. These microbubbles or nanoparticles are retained within regions of a specific disease process, thereby allowing phenotypic characterization of tissue. Since most of these tracers remain within the intravascular space, the disease processes assessed must be characterized by antigens that are expressed within the vascular compartment. Accordingly, the pathologic states that have been targeted include inflammation, ischemia-and tumor-related angiogenesis, and thrombus formation; all of which are mediated in part by molecular events within the vascular space. This review describes: 10 different strategies that have been employed to target ultrasound contrast agents to regions of disease, 2) the unique challenges for imaging targeted ultrasound contrast agents, and 3) some of the early experience imaging molecular events in animal models of disease.

Animals↗

PubMedDate not supplied

Contrast-enhanced power Doppler sonography: improved detection of characteristic flow patterns in focal liver lesions.

PURPOSE: The aim of this study was to evaluate whether intravenous injection of an ultrasound contrast agent aids in the visualization of focal liver lesions on power Doppler images. METHODS: Fifty patients with focal liver lesions were studied by B-mode and power Doppler sonography before and after intravenous injection of the contrast agent Levovist (galactose-based microbubbles; 10 ml of a concentration of 300 mg/ml). Thirty-two patients had malignant liver lesions (19 metastases, 12 hepatocellular carcinomas, 1 cholangiocellular carcinoma), while 18 had benign lesions (12 hemangiomas, 2 focal nodular hyperplasias, 4 others). RESULTS: After contrast medium injection, the number of lesions with no intralesional flow dropped from 18 to 9. Flow signal intensity was rated subjectively as marked on contrast-enhanced images in 17 patients; only 4 patients had marked flow on precontrast images. On precontrast studies, central flow in 10 lesions and peripheral flow in 29 lesions could be observed. After enhancement, the numbers increased to 18 and 34 lesions, respectively. CONCLUSIONS: On power Doppler images, a greater number of intratumoral vessels are seen in focal liver lesions after contrast medium administration.

Carcinoma, Hepatocellular↗

PubMed2000

Clinical evaluation of contrast-enhanced color Doppler sonography in the differential diagnosis of liver tumors.

PURPOSE: We investigated the value of contrast-enhanced color Doppler sonography in the differential diagnosis of liver tumors. METHODS: We prospectively examined 105 focal liver lesions in 100 patients by real-time gray-scale sonography, color Doppler sonography, and contrast-enhanced color Doppler sonography with galactose-based microbubbles (SH U 508A; Levovist). The final diagnoses of the liver lesions as confirmed by pathology or additional imaging techniques were 31 metastases, 25 hemangiomas, 19 hepatocellular carcinomas, 19 focal nodular hyperplasias, 2 cholangiocellular carcinomas, and 9 other lesions. RESULTS: Vascularity could be detected in 43 (41%) of the 105 lesions by conventional color Doppler sonography compared to 67 (64%) by contrast-enhanced color Doppler sonography. Contrast-enhanced color Doppler sonography identified moderate or extensive vascularity in all 19 focal nodular hyperplasias, moderate or extensive vascularity in 16 hepatocellular carcinomas and both cholangiocellular carcinomas, and no or minor vascularity in all but 3 hemangioma. The combination of gray-scale, conventional color Doppler, and contrast-enhanced color Doppler sonography led to the correct diagnosis in 81% of cases (85 of 105), compared to 57% (60/105) for gray-scale and conventional color Doppler sonography and 31% (33/105) for gray-scale sonography alone. CONCLUSIONS: Contrast-enhanced color Doppler sonography improves the detection of tumor vascularity and is useful in the differential diagnosis of liver lesions.

Confidence Intervals↗

PubMed1998

Colloidal gas aphrons: A novel approach to protein recovery.

Sebba (1987) defined colloidal gas aphrons (CGA) as microbubbles stabilized by surfactant layers, which are created by stirring surfactant solutions at speeds greater than a critical value. A high shear impeller is used for stirring and critical values for the impeller speed must be exceeded to create these stable gas liquid dispersions (typically >5000 rpm). Although there have been no previous reports of direct protein recovery using CGA, it is likely that, with appropriate choice of surfactant, proteins should adsorb to these surfactant bubbles by means of electrostatic and/or hydrophobic interactions. This is the basis of this study, in which the use of CGA for protein recovery from aqueous solution is considered. A surfactant which has been characterized previously for generation of CGA was chosen (Jauregi et al., 1997), i.e., the anionic surfactant sodium bis-(2-ethyl hexyl) sulfosuccinate (AOT). Lysozyme, a well-characterized protein, was chosen as the protein to be recovered. Lysozyme was recovered successfully from aqueous solution using CGA generated from AOT. At optimum conditions, lysozyme recovery, enrichment ratio, and separation ratio were 95%, 19 and 302 respectively, with enzyme activity maintained. These results indicate the exciting potential of this technique. A wide range of process conditions including initial concentration of protein and surfactant, surfactant/protein molar ratio, pH, and ionic strength were considered. High recoveries and enrichments were generally obtained at protein concentrations </=0.41 mg/mL, and surfactant concentrations >0.11 mg/mL. However, at high ionic strength (0.29M) poor separation and recoveries were obtained at low protein concentrations (counter-ions diminishing electrostatic interactions between protein and aphrons at this condition). In general, (ns/np)a was determined to be between 10 and 16 for experiments in which high levels of recovery/separation parameters were found. For most conditions, protein precipitation was observed; however, this precipitate could be resolubilized without loss of enzyme activity.

Chemistry Techniques, Analytical↗

PubMed1999

Strategy for the prevention and treatment of chronic lung disease of the premature infant.

Based on the analyses of approximately 1,000 infants with CLD, this condition was classified into 7 types according to the preceding illnesses and the chest X-ray appearance. The profile of inflammatory enzymes, cytokines and chemical mediators supported the relevance of the classification. Since different insults to the lung with different onsets exhibit the different spectra of the disease, appropriate strategies adapted to each type of CLD should be pursued. For types I and II prophylactic administration of exogenous surfactant, early enough to prevent the oxygen toxicity and barotrauma, is important. RDS can be diagnosed by the stable microbubble rating on gastric aspirates within several minutes of birth. The application of milder modes of ventilation such as HFOV started at birth should also be remembered. The recommended strategies for type IV and V are the care of the very low birth weight infant in the fully humidified incubator with careful fluid administration to prevent symptomatic PDA, and early detection and treatment of infection by screening with sensitive methods such as the APR score. However, the most difficult problem is to identify the correct strategy for type III and III', because these types of CLD can only be prevented by the complete eradication of intrauterine infection.

Chronic Disease↗

PubMed2000

Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen.

BACKGROUND AND OBJECTIVE: Selective photodamage of the retinal pigment epithelium (RPE) is a new technique to treat a variety of retinal diseases without causing adverse effects to surrounding tissues such as the neural retina including the photoreceptors and the choroid. In this study, the mechanism of cell damage after laser irradiation was investigated. STUDY DESIGN/MATERIALS AND METHODS: Single porcine RPE-melanosomes and RPE cells were irradiated with a Nd:YLF laser (wavelength lambda = 527 nm, adjustable pulse duration tau = 250 nsec-3 microsec) and a Nd:YAG laser (lambda = 532 nm, tau = 8 nsec). Fast flash photography was applied to observe vaporization at melanosomes in suspension. A fluorescence viability assay was used to probe the cells vitality. RESULTS: The threshold radiant exposures for vaporization around individual melanosomes and for ED50 cell damage are similar at 8-nsec pulse duration. Both thresholds increase with pulse duration; however, the ED50 cell damage radiant exposure is 40% lower at 3 microsec. Temperature calculations to model the onset of vaporization around the melanosomes are in good agreement with the experimental results when assuming a surface temperature of 150 degrees C to initiate vaporization and a homogeneous melanosome absorption coefficient of 8,000 cm(-1). Increasing the number of pulses delivered to RPE cells at a repetition rate of 500 Hz, the ED50 value decreases for all pulse durations. However, the behavior does not obey scaling laws such as the N 1/4 equation. CONCLUSION: The origin of RPE cell damage for single pulse irradiation up to pulse durations of 3 microsec can be described by a damage mechanism in which microbubbles around the melanosomes cause a rupture of the cell structure. The threshold radiant exposure for RPE damage decreases with increasing number of pulses applied.

Animals↗

PubMed2026

Microblasting Wound Dressings Mechanically Disrupt Polymicrobial Biofilms to Enhance Healing in Treatment-Resistant Wounds.

Treatment-resistant wounds driven by polymicrobial biofilms are a major clinical challenge, affecting millions globally and leading to chronic inflammation, persistent pain, and poor healing outcomes. These wounds are characterized by mature biofilms reinforced by dense extracellular polymeric substances, which confer strong tolerance to conventional treatments. Despite emerging technologies, such as nanoparticles, bacteriophages, and engineered enzymes, effective clearance of established biofilms remains challenging. Here, we develop a microblasting wound dressing (µBLAST) that delivers spatially confined mechano-chemical disruption at the tissue-biofilm interface to remove viscoelastic biofilm matrices and promote tissue regeneration. The µBLAST is assembled by embedding MnO2-doped diatom biosilica beneath an H2O2-releasing cellulose mesh, enabling localized catalytic microbubble generation within biofilm matrices. Confined expansion and rupture of oxygen bubbles produce localized mechanical stress sufficient to dislodge mature, antibiotic-resistant polymicrobial biofilms, while sustained H2O2 release prolongs particle activity. In a murine wound model infected with mature P. aeruginosa and methicillin-resistant S. aureus biofilms, µBLAST treatment significantly reduces biofilm burden, accelerates re-epithelialization, promotes hair regrowth, and mitigates inflammation. Moreover, µBLAST enhances antibiotic efficacy, suppressing biofilm regrowth even at ten-fold reduced drug doses. These findings highlight confined mechano-chemical biofilm disruption as a therapeutic strategy for treating mature, antibiotic-resistant biofilm infections and promoting tissue regeneration.

Biofilms↗

PubMed2001

Immobilization of Candida rugosa lipase on colloidal gas aphrons (CGAs).

A novel technique for immobilization of Candida rugosa lipase onto anionic colloidal gas aphrons (CGAs) is described. CGAs are spherical microbubbles (10-100 microm) composed of an inner gas core surrounded by a surfactant shell. In this initial study, greater than 80% lipase (w/w) was effectively retained on the CGAs. Leakage of protein from the CGAs and the activity of the adsorbed lipase decreased with increasing enzyme loading; this indicates that multilayers of lipase may be adsorbing onto the CGAs. The CGA-immobilised lipase displayed normal Michaelis-Menten dependence on substrate concentration and also exhibited greater activity than the free enzyme.

Biotechnology↗

PubMed1991

Contrast echocardiography and myocardial perfusion.

New clinical applications for myocardial contrast echocardiography (MCE) are being developed in both the operating room and the catheterization laboratory. Studies have shown that red blood cell transit time through the myocardium is a measure of myocardial blood flow. Sonicated albumin microbubbles can mimic intramyocardial behavior of red blood cells. Other studies have used MCE to assess collateral flow to determine myocardial viability after acute myocardial infarction. The authors have developed a computer system that allows on-line quantitation of contrast echocardiographic data in the operating room, and this system is able to confirm that bypass grafts are properly placed. The ability to quantitate myocardial flow with MCE may be useful in guiding the sequence of graft placement and for assessing the success of the operation. These measures will help lower the incidence of perioperative infarction. Experiments in our laboratory using the canine model have shown that MCE may be useful in assessing the intramyocardial distribution of retrogradely delivered cardioplegia. This technique may, therefore, assist the surgeon in determining the adequacy of retrograde cardioplegia delivery and may improve myocardial preservation during bypass surgery.

Albumins↗

PubMed1996

Evidence for a relation between inspired gas mixture and the left ventricular contrast achieved with Albunex in a canine model.

BACKGROUND: In a previous experiment, a marked reduction in the right- and left-sided contrast effect of Albunex was noted in an intubated animal spontaneously breathing isoflurane in 100% oxygen. The theory suggests that the time course of echogenicity of microbubbles in liquid is dependent on the pressure and the gradients of dissolved gases. The present set of experiments tested whether the loss of contrast occurs at commonly used therapeutic concentrations of inspired oxygen. HYPOTHESIS: This research tested the hypothesis that the left ventricular (LV) contrast effect achieved with intravenous injection of the ultrasound contrast agent Albunex is related to the inspired oxygen content. METHODS: Intubated dogs were maintained in a spontaneously respiring anesthetic state on isoflurane and mixtures of oxygen (12-50%) in nitrogen. FIO2 was held steady for 15 min prior to injection of 0.08 ml/kg of Albunex. The contrast effects were recorded from a transthoracic short-axis view. Left and right ventricular brightness curves were generated from digitized sequences of end-diastolic frames. The minimum and maximum brightness and area under the time-brightness curves were determined. RESULTS: The LV maximum brightness and area under the curve showed significant negative correlations (p = < 0.004) with the FIO2, while the minimum brightness showed a significant positive correlation (p = < 0.002). No significant correlations were found for the right ventricular brightness parameters. CONCLUSIONS: These findings show an important relationship between the FIO2 and loss of the contrast effect of Albunex. This loss occurs at oxygen concentrations in the therapeutic range, but could be overcome by increasing the dose of Albunex. The mechanism is likely related to an outward nitrogen gradient causing a loss of echogenicity. The clinical implication is that patients on supplemental oxygen may require higher doses of Albunex to achieve optimal opacification.

Albumins↗