Acoustic backscatter properties of the particle/bubble ultrasound contrast agent

Bubble-based suspensions with diameters in the 1-5 microns range have been developed for use as ultrasound contrast agents. Bubbles of these dimensions have resonance frequencies in the diagnostic ultrasonic range, thus improving their backscatter enhancement capabilities. The durability of these bubbles in the blood stream has been found to be limited, providing impetus for a number of approaches to further stabilize them. One of the approaches has been the development of micrometer-size porous particles or 'nano-sponges' with properties suitable for the entrapment and stabilization of gas bubbles. However, the complex morphology and surface chemistry involved in the production of this type of agent makes it unfeasible to directly measure the volume of the entrained gas. A model based on acoustic scattering principles is proposed which indicates that only a small volume fraction of gas should be necessary to significantly enhance the echogenicity of this type of particle-based contrast agent. In the model, the effective scattering cross-section is evaluated as a function of the volume fraction of gas contained in the overall scatterer and the overall scatterer diameter. Initially, the volume fraction of gas is considered as a discrete entity of single bubble. Using common mixture rules, it is then shown that the gas can be considered to be distributed throughout the particle and still arrive at a result that is similar to that for a single, discrete volume of gas. The main contribution to the increased scattering cross-section is due to the compressibility difference between gas and water. The backscatter coefficient is computed as the product of the resulting differential scattering cross-section and the scatterer number density. This approach facilitates comparison with known backscatter coefficients of biological targets such as liver and blood. Simple experimental results are presented for comparison with the model, and the implications relevant to clinical use are suggested.     

Conventional and hypobaric activation of an ultrasound contrast agent

Hypobaric activation is a new injection technique for use with the contrast agent EchoGen and, in this study, the agent's ability to produce parenchymal enhancement in vivo, with and without prior hypobaric activation, was investigated. Injections, ranging in dose from 0.05 to 0.5 mL/kg, were administrated through a peripheral vein to eight woodchucks with multiple hepatomas. At the 0.10 mL/kg dose level, seven of eight injections following hypobaric activation (88%) resulted in definite parenchymal enhancement. Conversely, dosages of 0.10 mL/kg without prior hypobaric activation produced no grey-scale changes. Only at the 0.4 and 0.5 mL/kg dosage level did the conventional administration technique obtain similar results (4 of 5 injections increased the echogenicity for a 0.4 mL/kg dose). These differences were statistically significant (p = 0.031). In vitro experiments were conducted to establish the physical mechanisms behind hypobaric activation. Relative measurements of contrast microbubble sizes were performed with a phase Doppler particle analyzer after hypobaric and after conventional (bolus) activation. Hypobaric activation produced approximately 20 times more microbubbles per unit volume than the conventional method. In conclusion, this investigation has demonstrated the benefits of prior hypobaric activation when performing in vivo contrast studies with EchoGen and determined the physical mechanisms behind this new injection technique. Hypobaric activation of EchoGen increases contrast enhancement and reduces dose size.     

Standard properties of ultrasound contrast agents

A standardization procedure for in vitro acoustic characterization of ultrasound contrast agents is presented. One new acoustic parameter for particular importance is retained: This is STAR, scattering-to-attenuation ratio, for quantification of the effectiveness of the contrast agent. The STAR expresses the ability of the contrast agent to enhance the visualization of the tissue containing the contrast agent and, at the same time, represents the degree of its absorption. So, it is desirable to produce a contrast agent with high STAR, having good scattering properties to improve the image visualization, and low attenuation to image the underlying biological structures and to avoid shadowing. In this study, we present methods for calculations and measurements of the STAR and comparison between different contrast agents.     

Gas-body-based contrast agent enhances vascular bioeffects of 1.09 MHz ultrasound on mouse intestine

Anesthetized hairless mice were exposed to continuous or pulsed 1.09-MHz ultrasound with or without prior injection of a gas-body-based ultrasound contrast agent. Albunex at a dose of 10 mL/kg increased the production of intestinal hyperemia, petechia and hemorrhages by continuous ultrasound. For pulsed ultrasound, with 10 micros pulses and 0.01 duty cycle, petechiae were produced for exposures as low as 1 MPa spatial peak pressure amplitude with added gas bodies. The enhancement of petechiae production was robust for pulsed exposure; for example, at 2.8 MPa, an average of 227 petechiae was obtained with added gas bodies, which was 30 times more than without the agent. The production of petechia was roughly proportional to the dosage of Albunex for pulsed exposure. Results did not appear to be strongly dependent on pulsing parameters, but long bursts (0.1 s) were somewhat more effective than pulses (10 micros). The observed vascular bioeffects appeared to involve both thermal and nonthermal mechanisms for continuous exposure, but to result primarily from gas-body activation for pulsed exposure.     

Preparation and characterization of echogenic liposome as an ultrasound contrast agent: size-dependency and stabilizing effect of cholesterol on the echogenicity of gas-entrapping liposome

The liposome entrapping CO2 gas inside the vesicle, which is called the echogenic liposome, has been made and characterized in vitro as an ultrasound contrast agent. The small unilamellar vesicle (SUV), large unilamellar vesicle (LUV) and multilamellar vesicle (MLV) as echogenic liposomes were compared in their echogenic efficiency and stability, and the effect of size and acoustic property was tested. The acoustic reflectivity increased with the increase in size of the vesicle, largest for the gas filled MLV among the three liposome suspensions. The acoustic reflectivity obtained with the echogenic MLV was larger than that of the gas bubbles enclosed within a surfactant mixture. A half-lifetime of 39 min was observed for the MLV prepared from egg-yolk phosphatidylcholine liposomes. The duration of reflectivity was prolonged drastically to a half-lifetime of 866 min by incorporating cholesterol into the MLV, although the echogenicity was decreased by such incorporation. The stabilizing effect of cholesterol for the ordinary liposomal membrane was thus ascertained in the present case of the gas-entrapping liposome. Our findings encourage the future development of improved gas-entrapping liposomes for the clinical trials of ultrasound contrast agents.     

Human biodistribution of an ultrasound contrast agent (Quantison) by radiolabelling and gamma scintigraphy

The biodistribution and kinetics of an air filled human serum albumin microcapsule formulation (Quantison) intended for use as an intravenous ultrasound contrast agent have been examined. 12 healthy subjects were administered with approximately 50 million microcapsules per kilogram body weight, radiolabelled with 50 MBq 123I. Imaging was performed over a period of 58 h using a large field-of-view gamma camera and the amount of labelled material present in the blood, urine and faeces measured. Imaging demonstrated that the liver was the organ with the highest uptake, with a mean uptake of 41.8% (SD 10.4%) of the administered dose 1 h following administration. The maximum uptake of the agent in the lungs was low, mean 4.0% (SD 3.4%). A small amount of uptake was visible in the bone marrow; however, this was not quantifiable. There was also evidence of minimal myocardial activity within 5 min of administration. No adverse events were observed and there were no changes in any of the individual post-study indices. The present study demonstrates the safety of Quantison. Gamma scintigraphy played a useful role in confirming the biodistribution of the agent with little lung uptake, high liver uptake and evidence of myocardial uptake.     

反应物中氧化剂和掺杂剂浓度对聚苯胺性能与结构的影响

采用红外光谱、X射线衍射、透射电子显微术结合电导率测量,研究了以过硫酸铵为氧化剂,十二烷基苯磺酸为掺杂剂,通过乳液聚合法合成的聚苯胺的性能与结构.实验中发现:聚苯胺的电导率随合成时氧化剂、掺杂剂与苯胺相对比例的改变而发生明显变化,并在某一比例达到峰值,同时伴随有红外光谱某些特征峰峰位与峰高的相对变化,而晶化程度也随合成条件不同而呈现差异,性能最佳的聚苯胺的微观形貌呈纤维状,对应于最大的晶化程度,接近于中间氧化态.这些结果表明:氧化与掺杂条件的变化影响到聚苯胺中苯环与醌环的相对比例、聚苯胺链的排列有序度,而这些也是影响聚苯胺电导率的重要因素.     

Experimental ultrasound contrast study of the myocardium]

The ultrasound contrast medium obtained by the original methods was administered into the left ventricular cavity and myocardium of 12 open-chest dogs by using a catheter. After its administration into the cavity there was its intensive contrast. When the ultrasound contrast was administered into the aortic root, the entire myocardium contrasted, on selective administrations of the contrast into the coronary arteries, the beds supplied by appropriate arteries contrasted. The ultrasound contrast study enabled the areas with impaired perfusion as echo-negative "filling defects" to be detected and mapped. The imaging of myocardial blood flow in tomographic sections and real time allows one to regard it promising for clinical use.     

The effect of nitroglycerine medication on the arterial oxygen pressure in obstructive lung disease

Nitroglycerine gains increasing interest because of its favourable hemodynamic effects in patients with left heart failure, especially in those with coronary heart disease. The drug-induced vasodilatation and lowering of pulmonary arterial pressure, is followed by a redistribution of lung perfusion which occasionally may be deletarious. It is shown that in patients with obstructive lung disease, a significant drop in arterial oxygen tension may be observed. This could be due to increased perfusion of the lung, without a concommitant augmentation of ventilation, which results in an increase of right to left-shunt.     

桡动脉与股动脉穿刺置管在有创血压监测中的应用效果比较

目的 探索一种穿刺成功率更高、安全且并发症较少的动脉穿刺置管的路径.方法 对ICU收治的617例患者随机分为采取桡动脉或股动脉穿刺置管组,对2组病例进行分析,并对临床效果进行评价.结果 2组穿刺采血方法成功率、血管并发症、患者舒适状况差异均存在统计学意义(P＜0.01).结论 桡动脉穿刺置管成功率较高,血管并发症少,同时可以减轻患者痛苦,值得在临床工作中推广.     

In vivo relaxometry of three brain tumors in the rat: effect of Mn-TPPS, a tumor-selective contrast agent

The spectral frequency response, frequency response range, and volume control linearity of five telephone amplifiers were examined using real-ear measures. All measurements were performed in KEMAR's (Knowles Electronics Manikin for Acoustic Research) ear canal using a composite speech-shaped waveform as the stimulus. Spectral frequency response and response range of each device was obtained at four volume control settings and compared to those of a standard telephone receiver. Only two of the amplifiers replicate the spectral frequency response of the standard receiver and show an increase in the amount of gain provided with increasing volume control rotation. The remaining three amplifiers show a more restricted spectral frequency response and response range when compared to those of the standard receiver. The volume control characteristics of the amplifiers were somewhat more uniform. Overall results indicate that the spectral frequency response and response range of telephone amplifiers can be objectively evaluated using real-ear measures, and these measures are essential in determining the usefulness of certain telephone amplifying devices.     

Relation of contrast echo intensity and flow velocity to the amplification of contrast opacification produced by intermittent ultrasound transmission

Intermittent ultrasound transmission during contrast echocardiography, so-called transient response imaging (TRI), amplifies contrast intensity. This effect of TRI is attributed to decreased microbubble destruction by reduced exposure time to ultrasound energy. The present study examined the hypothesis that the signal amplification produced by TRI is related to the baseline intensity present in the image and the velocity of flow. We performed second harmonic (2.5/5.0 MHz) imaging during both continuous (frame rate 55 Hz) and electrocardiogram-triggered TRI mode. Contrast images produced by perfluorohexane microbubbles (AF0150) in a steady flow model were obtained every minute throughout the decay phase at transit velocities of 8.1, 6.2, 3.4, 1.9, and 0.7 cm/sec. The decay of videointensity over time could be fitted to a sigmoid curve for both imaging modes with r > 0.99 for individual velocities. The intensity with TRI was greater than that with continuous imaging (CI) at any time and velocity. The mean increase in intensity between modes throughout decay was 8.2 +/- 3.7, 12.8 +/- 4.2, 25.7 +/- 5.8, 49.5 +/- 8.0, and 64.0 +/- 14.4 gray levels for the respective velocity levels studied (p < 0.0001). Although varying with baseline intensity at early and late phases, the TRI amplification plateaued during middecay, and within the intensity range of 16 to 143 gray levels for CI and 67 to 186 gray levels for TRI, it showed no overlap among the different velocity levels. Thus the ability of TRI to enhance contrast opacification is much greater at low flow velocities, which has implications regarding the mechanism of TRI effect and preferential visualization of intramyocardial coronary arteries by this agent. Although this effect was influenced by the baseline intensity, it was relatively constant for each velocity level within an optimal intensity range during middecay, providing the basis for flow velocity measurement by contrast echo.     

On the spreading of grain boundary dislocations and its effect on grain boundary properties

The effect of dissociation of trapped lattice dislocations (TLDs) on the energy of grain boundaries (GBs) is calculated. Two possible effects are considered. The first is the change of energy of the GBs caused by the presence of TLDs cores. It was shown to be smaller than 5% of the grain boundary energy. The other, more important, is an increase of the energy of the strain fields connected with grain boundaries. Dissociation of TLDs causes an increase of incompatibility strains between plastically deformed grains. The energy of these strains is of the order the GB energy in equilibrium. The EGBDs strain fields provide a driving force for GB sliding and migration. In fact, EGBDs cannot leave the grain boundaries. Recovery of these dislocations can take place only by sliding and migration of grain boundaries.     

Temporal contrast and the word frequency effect.

Studied the word frequency effect in recall and recognition under 3 list structures: (a) homogeneous rare or common nouns, (b) mixed alternating frequencies, and (c) mixed blocked frequencies. Exp I with 96 undergraduates found that the number of frequency contrasts within a list had a clear effect on recall and little effect on recognition. Recall of rare items was poor in a homogeneous list, equal to common items in a blocked list, and better than common items when in a list of alternating frequencies. Exp II with 48 Ss examined the reversed frequency effect of the alternating list under overt and covert rehearsal conditions across 3 trials. Under overt rehearsal there was no significant difference in number of rehearsals of rare and common items. The superior recall of rare items present on Trial 1 decreased across trials supporting a stimulus change-contrast interpretation of the effect of mixed frequency items in free recall. (French summary) (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of dietary sodium intake on the blood pressure and cardiac output responses to angiotensin II in unanaesthetized rats

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.     

The effect of high pressure insertion and antibiotic inclusions upon the mechanical properties of polymethylmethacrylate

The properties of self-curing polymethylmethacrylate as affected by the admixing of an antibiotic to the powder-liquid mixture and as affected by insertion technique demonstrated that the antibiotic agent may leach from the surface of the acrylic, but not necessarily from the interior. The compressive and tensile strength, determined on two different commercial formulations, suggests that the antibiotic additive is not detrimental to the mechanical properties. A high pressure insertion technique produces a significant improvement in the mechanical properties of the self-curing acrylic material.     

Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound

Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions.