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Exceptional survival of a patient with large ventricular septal defect, bidirectional shunt, and severe pulmonary valve stenosis.

A 74-year-old man has survived in good health for an exceptionally long time despite the presence of a moderate-to-large-sized membranous ventricular septal defect (VSD). He has remained acyanotic with New York Heart Association class I function. Transthoracic and transesophageal echocardiography with color flow Doppler demonstrated a membranous VSD with left-to-right and right-to-left bidirectional shunts during ventricular systole and diastole, respectively, with an right ventricular systolic pressure of 93 mm Hg, dilation of the atria and the right ventricle, and right ventricular hypertrophy. The pulmonary valve was severely stenotic with transpulmonary valve peak velocity of 6.1 m/s and a peak pressure gradient of 147 mm Hg. The pulmonary artery and inferior vena cava were mildly dilated, and the left ventricular dimension and systolic function were normal. Transesophageal echocardiography with saline solution microbubble injection demonstrated positive contrast effect in the left ventricle in diastole confirming a right-to-left shunt at the ventricular level. This man is currently the oldest survivor with a moderate-to-large-sized membranous VSD reported in the literature.

Aged↗

The role of quantitative myocardial contrast echocardiography in the study of coronary microcirculation in athlete's heart.

Quantitative myocardial contrast echocardiography was performed with harmonic power Doppler analysis using the background subtraction and Levovist (Schering AG, Berlin, Germany) as contrast agent in a triggered modality. Quantitative analysis of echocontrast was performed offline with PC software, obtaining the transit curves of microbubbles through the coronary capillary system. Coronary microcirculation in athletes showed a behavior substantially comparable with control participants, although at a higher level. Training determines a physiologic left ventricular hypertrophy that counterbalances the dilatation in the left ventricular chambers because of the higher blood volume in athletes compared with control participants. Angiogenesis and several functional adaptations (relaxation of small coronary arteries, increased production of nitric oxide by the coronary endothelium, or both), represent the potential mechanisms that allow an optimal distribution of oxygen and of substrates to the hypertrophied myocardium of the athletes.

Adult↗

Does contrast echocardiography with Optison induce myocardial necrosis in humans?

Myocardial contrast echocardiography is a promising diagnostic tool for detecting microvascular integrity. Multiple experimental laboratories have shown that diagnostic combined microbubble contrast and ultrasound exposure can cause vessel rupture and myocardial damage in laboratory animals. This study investigated the phenomenon of contrast ultrasonically induced myocardial damage in human beings. Twenty consecutive patients (mean age of 60 +/- 12 years, 14 men) underwent contrast echocardiography with intravenous Optison using a mechanical index of at least 1.4 (Vivid Five System (GE, Vingmed Ultrasound, Horton, Norway). Creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB); CK-MB mass, myoglobin, and troponin I were measured before and 2, 4, 8, and 24 hours after contrast echocardiography. There was no significant correlation concerning the response to contrast echocardiography for any pair of parameters at any time after the intervention. Only in 2 patients were there higher values for troponin I before and after contrast echocardiography without an increase of myoglobin, CK, or CK-MB mass and activity. These values were therefore interpreted as false positive because of renal failure and severe heart failure. The use of contrast echocardiography is without demonstrated risk of myocardial damage even in patients with different cardiologic entities.

Aged↗

Radio frequency dual-spectra analysis of regional myocardial perfusion: Comparison with harmonic densitometric method.

Our objective was to compare harmonic-to-fundamental frequency ratio peak (HFRp) analysis with conventional harmonic gray-scale densitometric analysis on the basis of ability to eliminate heterogeneity in ultrasound signals. Broadband radio frequency and harmonic data were obtained by using intermittent short-axis scans in 10 open-chest pigs before and during infusion of contrast microbubbles. HFRp and gray-scale intensity values were measured in 6 segments of left ventricular myocardium. In baseline images, the influence of anisotropy on HFRp values was significantly less than that in gray-scale intensities. In perfusion assessment with subtraction, contrast heterogeneity in HFRp values was significantly smaller than that in gray-scale intensities. The increase in HFRp values after subtraction was significantly greater than that in gray-scale intensities in lateral (P <.001), posterior (P <.0001), and inferior (P <.01) myocardium. HFRp analysis can compensate for baseline myocardial anisotropy and regional contrast heterogeneity. With background subtraction, HFRp analysis allows better quantification of myocardial perfusion.

Absorptiometry, Photon↗

Effect of destructive pulse duration on the detection of myocardial perfusion in myocardial contrast echocardiography: In vitro and in vivo observations.

UNLABELLED: Myocardial perfusion is detected with contrast echocardiography by comparing a contrast-enhanced image with a baseline obtained before contrast injection (true baseline) or after myocardial bubble destruction after a high-power destructive pulse (postdestructive pulse baseline). Although it is assumed that all bubbles are destroyed by a destructive pulse insuring optimal contrast detection, this assumption has not been tested. In 18 participants we compared the videointensity (VI) differences among the contrast-enhanced image, the postdestructive pulse baseline, and the true baseline using both triggered high-mechanical index imaging and real-time imaging. VI difference was significantly greater for the true baseline with both techniques at all ventricular levels. The benefit of using a true baseline was less when the duration of the destructive pulse was increased. Similarly, we quantified VI in a flow phantom using continuous Optison (commercially available perfluoropropane-filled albumin microbubbles) (Amersham, Princeton, NJ) infusion and variable durations of destructive pulses. VI decreased with the duration of the destructive pulse and reached a plateau after a duration of 8 to 15 frames. The plateau reached after a long destructive pulse was dependent on flow rate and concentration and never reached a true baseline, unless concentration (<100 microL/L) and flow rate (<0.5 cm/s) were very low. IN CONCLUSION: (1) in clinical studies, the difference in VI between contrast-enhanced and baseline images is greater when true baseline is used; (2) the longer the destructive pulse, the closer the postdestructive pulse baseline to true baseline; and (3) this effect exists in all regions of the left ventricle.

Adult↗

Heterogeneity of contrast effect during intermittent second harmonic myocardial contrast echocardiography in healthy patients.

Intermittent harmonic imaging with contrast is increasingly used to detect perfusion defects in patients with coronary disease. To achieve this, image homogeneity and the ability to visualize segments on the lateral and distal portions of the imaging field are important. The objective of this study was to evaluate whether the use of specific postprocessing algorithms, such as background subtraction with color coding and parametric display, allows for improved image homogeneity compared with conventional intermittent second harmonic imaging. For this purpose, 20 participants who were free of cardiac abnormalities and in whom myocardial perfusion should by definition be homogeneously distributed, underwent contrast echocardiography during the constant intravenous infusion of 1.0 +/- 0.3 mL/min of perfluorocarbon-enhanced sonicated dextrose albumin. End-systolic ECG-triggered images were obtained from the apical 4-chamber view at pulsing intervals of 300-ms 1, 3, 5, and 8 cardiac cycles. For analysis, each set of images was aligned, averaged, background subtracted, and color coded. Pulsing intervals versus videointensity plots were then generated for each pixel in the images and fitted to an exponential function to produce parametric images of beta (an index of microbubble velocity) and A (a measure of myocardial blood volume). The heterogeneity of the contrast effect was evaluated by computing the coefficients of variation in each image. Contrast heterogeneity was >20% with all 4 methods. However, it was greater in gray-scale second harmonic (39 +/- 13%) and color-coded (47 +/- 16%) images than in parametric images of beta and A (24 +/- 14 and 24 +/- 8%, respectively; both P <.05 vs gray-scale second harmonic and color-coded images). With all 4 methods, basal- and apical-lateral segments contributed most to image heterogeneity, albeit significantly less so with parametric imaging. In conclusion, our data indicate that myocardial opacification is frequently heterogeneous in healthy participants, particularly when using gray-scale second harmonic and background-subtracted with color-coding imaging. Parametric imaging allows reduction, albeit incomplete, of the heterogeneity of the contrast effect and therefore improves image quality.

Adult↗

A bubble-driven microfluidic transport element for bioengineering.

Microfluidics typically uses channels to transport small objects by actuation forces such as an applied pressure difference or thermocapillarity. We propose that acoustic streaming is an alternative means of directional transport at small scales. Microbubbles on a substrate establish well controlled fluid motion on very small scales; combinations ("doublets") of bubbles and microparticles break the symmetry of the motion and constitute flow transport elements. We demonstrate the principle of doublet streaming and describe the ensuing transport. Devices based on doublet flow elements work without microchannels and are thus potentially cheap and highly parallelizable.

Acoustics↗

Preoperative assessment of gastric cancer vascularity by flash echo imaging.

BACKGROUND: Tumor vascularity as indicated by immunohistochemical staining is a significant prognostic factor in gastric and other cancers. Non-invasive preoperative assessment of the vascularity of gastric cancers has not been possible. We aim to determine the reliability of harmonic flash echo imaging (FEI) for assessment of vascularity of gastric cancers by comparison with CD34 staining of resected specimens. METHODS: Twelve patients undergoing surgical resection of advanced gastric cancer were studied. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images. Using the tumor image showing strongest enhancement in each FEI series, regions of interest were determined to measure mean echo intensity in the tumor. Immunohistochemistry using antibodies against CD34 was carried out in resected specimens. Tumor vascularity was determined by counting stained microvessels. RESULTS: A significant positive correlation was noted between sonographic amplitude determined preoperatively by FEI analysis and number of CD34-stained microvessels in tumor specimens (r = 0.869, P = 0.004). CONCLUSION: Vascularity of gastric cancers now can be evaluated non-invasively by harmonic FEI.

Antigens, CD34↗

Suspected fatal venous air embolism during anaesthesia in a Pomeranian dog with pulmonary calcification.

CASE HISTORY: Death occurred in a 1.25 kg, 9-month-old female Pomeranian dog undergoing anaesthesia for surgical repair of partially healed fractures of the radius and ulna. CLINICAL FINDINGS: Following sedation, anaesthesia was induced using thiopentone and maintained with halothane in oxygen. An acute decrease in the dog's end-tidal carbon dioxide (EtCO2) measurements was noted approximately 50 min after induction, immediately following delivery of a 5-ml bolus of lactated Ringer's solution (LRS) administered to flush a small (0.06 ml) volume of fentanyl via a pre-placed intravenous (I/V) catheter. Venous air embolism (VAE) was suspected and the dog died despite interventive therapy. On post-mortem examination, several air bubbles were noted when the right ventricle was opened under water. Histologically, the kidneys appeared abnormal with immature glomeruli, and the lungs appeared diffusely mineralised. The origin of the air was probably small bubbles and microbubbles that may have been present in the extension set and 20 ml syringe used for the administration of fentanyl and I/V fluids to the dog. DIAGNOSIS: Renal dysplasia and diffuse pulmonary calcification, with VAE as the probable cause of death. CLINICAL RELEVANCE: In this case of VAE-associated anaesthetic death, it is further speculated that underlying pulmonary disease, in the form of pulmonary calcification, may have contributed to an increased sensitivity to the adverse effects of VAE.

Anesthesia↗

Observational case reports of intra- and postoperative ultrasound monitoring of uterine balloon ablation.

Uterine balloon ablation (UBT) is an established treatment of women with menorrhagia. Success rates in terms of amenorrhoea following UBT vary between about 15 and 40%. The aim of these case reports was to attempt to explain some of the reasons behind the low amenorrhoea rate as well as the variation seen in outcome. This was facilitated by intraoperative ultrasound observation of the position of the heater element within the uterine cavity, including its proximity to the endometrial walls and the direction of microbubbles produced by the heater element. These findings were then correlated with postoperative ultrasound findings and clinical outcome. The position of the balloon catheter within the uterine cavity varied and we hypothesise that this may have an effect on outcome. A thin postoperative endometrium on ultrasound signifies successful ablation, yet is not always associated with a cessation of troublesome menorrhagia, nor patient satisfaction.

Adult↗

Contrast-enhanced color Doppler ultrasonography in suspected parathyroid lesions.

PURPOSE: To assess the usefulness of US contrast media in the evaluation of patients with primary hyperparathyroidism, with a nodule showing US features of a primary parathyroid lesion but lacking the color Doppler US appearance of a parathyroid mass. MATERIAL AND METHODS: Thirteen patients (7 female, 6 male; age range 51-79 years) were examined with US before and after administration of a stabilized galactose-based microbubble contrast agent. Ten patients underwent surgery and the final histological examination demonstrated parathyroid adenoma in 9 cases and a mesenchymal benign nodule in 1 case. Three nodules were proved to be of thyroid origin at fine-needle aspiration biopsy. RESULTS AND CONCLUSION: The use of a US contrast agent resulted in a diagnostic gain compared to unenhanced studies in 12/13 cases. Color Doppler findings characteristic of parathyroid lesions were observed in 7/13 cases, of thyroid nodules in 4/13 cases, and nonspecific patterns in 2/13 cases. Contrast-enhanced color Doppler US can be proposed in selected patients in whom unenhanced color Doppler provides uncertain findings. Its ideal application should be the evaluation of cervical lesions without detectable intranodular flow at unenhanced Doppler studies. In these cases, the contrast agent helps in visualizing typical color Doppler signals of the parathyroid lesions ("vascular pole" and "mixed pattern").

Adenoma↗

Computerized image analysis of bubbles in gastric aspirate for prediction of respiratory distress syndrome.

UNLABELLED: Gastric aspirates were obtained from 80 newborn babies (gestational age 24-34 wk). Fifteen of these babies developed respiratory distress syndrome (RDS). Bubbles were generated in the samples by vigorous suctioning and the number and size distribution of the bubbles were determined in random fields by computer-aided image analysis. Sensitivity and specificity for prediction of RDS were 87% and 78% for average diameter of bubbles (cut-off points >45 microm) and similar for the proportion and total number of microbubbles (diameter <20 microm). CONCLUSION: Computerized image analysis of bubbles in gastric aspirate can be used for non-biased prediction of RDS in newborn babies.

Gases↗

Reducing liposome size with ultrasound: bimodal size distributions.

Sonication is a simple method for reducing the size of liposomes. We report the size distributions of liposomes as a function of sonication time using three different techniques. Liposomes, mildly sonicated for just 30 sec, had bimodal distributions when surface-weighted with modes at about 140 and 750 nm. With extended sonication, the size distribution remains bimodal but the average diameter of each population decreases and the smaller population becomes more numerous. Independent measurements of liposome size using Dynamic Light Scattering (DLS), transmission electron microscopy (TEM), and the nystatin/ergosterol fusion assay all gave consistent results. The bimodal distribution (even when number-weighted) differs from the Weibull distribution commonly observed for liposomes sonicated at high powers over long periods of time and suggests that a different mechanism may be involved in mild sonication. The observations are consistent with the following mechanism for decreasing liposome size. During ultrasonic irradiation, cavitation, caused by oscillating microbubbles, produces shear fields. Large liposomes that enter these fields form long tube-like appendages that can pinch-off into smaller liposomes. This proposed mechanism is consistent with colloidal theory and the observed behavior of liposomes in shear fields.

Light↗

Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery.

The unique behavior of perfluorocarbons (PFCs), including their high oxygen dissolving capacity, hydrophobic and lipophobic character, and extreme inertness, derive directly, in a predictable manner, from the electronic structure and spatial requirements of the fluorine atom. Their low water solubility is key to the prolonged in vivo persistence of the now commercially available injectable microbubbles that serve as contrast agents for diagnostic ultrasound imaging. Oxygent, a stable, small-sized emulsion of a slightly lipophilic, rapidly excreted PFC, perfluorooctyl bromide (perflubron), has been engineered. Significant oxygen delivery has been established in animal models and through Phase II and III human clinical trials. However, an inappropriate testing protocol and the lack of funding led to temporary suspension of the trials.

Blood Substitutes↗

Counterflow co-flocculation flotation for water purification.

A new method for potable water treatment was brought forward and studied in this research. The treatment process was named as counterflow co-flocculation flotation (CC-FF). Pilot experiment was conducted and the operational parameters were presented. The optimized operational conditions are as follows: the detention time is 6-11 min with hydraulic load of 9-16 m3/(m2 h); the recycle ratio should be no less than 8% while the distance between the inlet of source water and recycle water should be greater than 1200 mm. If the source water turbidity was lower than 100 NTU, 0.12-0.35 mmol/L Al dosage is enough to maintain efficient turbidity removal. Since the flocculation and flotation processes were carried out in the same tank, this new technique has some advantages than the conventional flocculation-flotation methods. Firstly, the microbubbles released from recycle water will participate in the flocculation of suspended particles, hence the low-density but high shear-force-resistance flocci could be formed. Secondly, the microflocci or suspended particles will be functioned as 'nucleus' during the bubble formation from air-dissolved recycle water. Thirdly, in the midsection of the tank a blanket of bubble-microfloc aggregates could be formed, which will intercept the downward-flow flocci and upward-flow bubbles efficiently, thus keep the renovation and stability of the blanket.

Conservation of Natural Resources↗

An in vitro system for the study of ultrasound contrast agents using a commercial imaging system.

An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter.

Contrast Media↗

A numerical study of transcranial focused ultrasound beam propagation at low frequency.

The feasibility of transcranial ultrasound focusing with a non-moving phased array and without skull-specific aberration correction was investigated using computer simulations. Three cadaver skull CT image data sets were incorporated into an acoustic wave transmission model to simulate transskull ultrasound wave propagation. Using a 0.25 MHz hemispherical array (125 mm radius of curvature, 250 mm diameter, 24 255 elements), the simulated beams could be focused and steered with transducer element driving phases and amplitude adjusted for focal beam steering in water (water-path). A total of 82 foci, spanning wide ranges of distance in the three orthogonal dimensions, were simulated to test the focal beam steering capability inside the three skulls. The acoustic pressure distribution in a volume of 20 x 20 x 20 mm(3) centred at each focus was calculated with a 0.5 mm spacing in each axis. Clearly defined foci were retained through the skulls (skull-path) in most cases. The skull-path foci were on average 1.6 +/- 0.8 mm shifted from their intended locations. The -3 dB skull-path beam width and length were on average 4.3 +/- 1.0 mm and 7.7 +/- 1.8 mm, respectively. The skull-path sidelobe levels ranged from 25% to 55% of the peak pressure values. The skull-path peak pressure levels were about 10%-40% of their water-path counterparts. Focusing low-frequency beam through skull without skull-specific aberration correction is possible. This method may be useful for applying ultrasound to disrupt the blood-brain barrier for targeted delivery of therapeutic or diagnostic agents, or to induce microbubbles, or for other uses of ultrasound in brain where the required power levels are low and the sharp focusing is not needed.

Body Burden↗

Intracardiac echocardiographic guidance and monitoring during percutaneous endomyocardial gene injection in porcine heart.

In an effort to develop a guiding and monitoring tool for transmyocardial gene transfer, we have evaluated the feasibility of intracardiac echocardiography (ICE) to guide percutaneous endomyocardial gene transfer (PEGT), and monitor complications, in a pig model. ICE (5.5-10 MHz), complemented by fluoroscopy, was utilized to guide a needle injection into the heart in 19 normal pigs. Using this system, we injected Evans blue dye into eight pigs (group I), a mixture of pCK-CAT plasmid and India ink into seven pigs (group II), and pCK-LacZ plasmid into four pigs (group III). In all pigs, ICE contributed to the injection procedure by guiding the catheter to anatomically distinct sites, and by assisting stabilization of the catheter-endocardial contact. ICE predicted the injection sites correctly in 56 of 64 sites (87.5%) in group I, and in 42 of 42 sites (100%) in group II. Leakage of injectate into the left ventricular cavity could be detected by the microbubbles generated. The sites of injections appeared as foci of bright myocardial echodensity, which persisted until the end of the procedure. The procedures were not associated with significant morbidity or mortality. The expression of the chloramphenicol acetyltransferase (CAT) gene was identified in 40 sites from 42 injections (95.2%) in group II. In group III, histology showed positive beta-galactosidase staining of myocytes limited around the needle track with low transfection efficiency (<1%). These results suggest that real-time ICE monitoring proves safe and useful during PEGT for guiding needle injection, monitoring leakage, ensuring delivery of injectate into the myocardium, and instantly diagnosing cardiac complications, resulting in successful gene transfer.

Animals↗