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Noninvasive assessment of renal artery stenosis: current imaging protocols and future directions in ultrasonography.

Doppler ultrasound is one of many modalities that have been evaluated for the detection of renal artery stenosis. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories have, however, prevented universal acceptance of this technique as a reliable screening test for renal artery stenosis. The recent introduction of ultrasound contrast agents has substantially expanded the potential of color Doppler ultrasound. The use of microbubble echoenhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. Moreover, contrast-enhanced Doppler ultrasound can provide functional information through analysis of renal time-intensity wash in/wash out curves. State-of-the-art contrast-enhanced Doppler ultrasound seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension.

Blood Flow Velocity↗

Doppler ultrasonography of peripheral vascular disease: the potential for ultrasound contrast agents.

Noninvasive diagnosis of peripheral vascular disease started with the introduction of Doppler technology. The development of high frequency ultrasound and color Doppler imaging allows continuous assessment of vascular disorders along the arterial tree. However, the technique remains operator dependent. It also suffers from anatomic limitations, such as bowel gas and ultrasound attenuation due to depth or wall calcification. Ultrasound contrast agents increase the Doppler signal intensity and should therefore reduce the rate of technical failures. They are useful for detecting the flux in cases of attenuated ultrasound beam and reduced blood flow. Their administration using continuous infusion protocols increases the duration of the effect. New imaging modalities such as harmonic imaging and pulse inversion imaging reduce Doppler artifacts and allow real time detection of the microbubbles flowing in the blood stream. Future directions include ultrasound-guided therapy of occlusion using encapsulated drugs targeted to the thrombus.

Blood Flow Velocity↗

Detection of tissue injury after extracorporeal shockwave lithotripsy of gallstones.

We evaluated seven patients undergoing gallstone lithotripsy for evidence of hepatic or renal trauma after each of 10 lithotripsy treatments. Postlithotripsy magnetic resonance imaging (MRI) and sonography showed no evidence of hepatic or renal injury as compared with baseline studies. Four treatments resulted in sonographic evidence of gaseous hepatic microbubbles (analogous to "the bends") due to cavitation effects of the shockwaves. Three of these four treatments produced serum glutamicoxaloacetic transaminase and -pyruvic transaminase elevation. One patient had microscopic hematuria. Minimal tissue damage results from gallstone lithotripsy. MRI and ultrasound, performed after lithotripsy, appear to be less sensitive than transaminasemia in detecting this low-grade injury.

Adult↗

Ventricular septal rupture after acute myocardial infarction: diagnosis by two-dimensional echocardiography.

A 69-year-old woman had ventricular septal rupture after acute anterolateral myocardial infarction. The defect was demonstrated directly by two-dimensional echocardiography. The appearance of negative contrast in the right ventricle during systole and microbubbles traversing the defect from right to left during diastole further confirmed the rupture. Two-dimensional echocardiography also accurately characterized the nature and extent of associated myocardial damage.

Aged↗

An investigation into the risk of air embolus during veno-venous bypass in orthotopic liver transplantation.

After observing micro-bubble activity in the venovenous bypass system during liver transplantation, an experiment was designed to investigate the origin of these bubbles and to define the conditions under which they occurred. Using a Biomedicus constrained vortex pump and a customized circuit design, microbubble activity was measured in saline and blood media during varying pre- and post-head pressures. The data show that air emboli can be generated from this pump and the rate at which they develop is directly related to the pre- and post-head pressure and hematocrit.

Anastomosis, Surgical↗

Ultrasound contrast imaging research.

This article is a review of the research on ultrasound contrast agents in general imaging. While general imaging contrast agent applications are still undergoing investigation and waiting FDA approval in the United States, they are approved for clinical use in Europe and other countries. The contrast microbubble properties are described, including their nonlinear behavior and destruction properties. Imaging techniques like harmonic imaging, pulse inversion, power pulse inversion, agent detection imaging, microvascular imaging, and flash contrast imaging are explained. A connection is made between the aforementioned imaging techniques and the different contrast agents available. The blood flow appearance of different liver tumors in the presence of contrast agents is demonstrated with examples.

Contrast Media↗

Myocardial perfusion by contrast echocardiography: diagnosis of coronary artery disease using contrast-enhanced stress echocardiography and assessment of coronary anatomy and flow reserve.

The advent of intravenous contrast agents, and newer ultrasound technology to enhance their detection, promises to improve and augment our conventional stress echocardiographic practice by improving diagnostic accuracy and providing novel information regarding myocardial perfusion and functional assessment of the coronary vasculature. The combination of intravenous contrast and harmonic stress echocardiography is a powerful tool for improved wall motion analysis through enhanced image quality, routinely permitting the evaluation of patients with suboptimal images. In this era of cost containment, we await studies in large populations addressing resource utilization and cost-effectiveness to determine if, indeed, all patients presenting with stress echocardiography should receive contrast. Myocardial perfusion can be observed using the technique, but the complex interactions of microbubbles and ultrasound in patients must be understood more fully before its implementation becomes routine practice. Non-invasive imaging of coronary arteries using contrast-enhanced transthoracic harmonic echo/Doppler promises to expand the field of diagnostic and experimental echocardiography, bringing new insight into the pathophysiology of ischemic and non-ischemic heart disease. The continued development of newer contrast agents and refinement of ultrasound imaging equipment ensures that the applications of contrast echocardiography in the assessment of CAD will continue to increase.

Contrast Media↗

Does repeated hyperbaric exposure to 4 atmosphere absolute cause hearing impairment? Study in Guinea pigs and clinical incidences.

HYPOTHESIS: Direct pressure applied on the inner ear cannot induce hearing loss. BACKGROUND: Three possible causes have been described in the literature for inner ear permanent lesions during scuba diving: pressure imbalance between the middle ear and the external ear, appearance of microbubbles in the internal ear, and direct effect of pressure on the inner ear. We seek to determine whether this last factor can be involved. METHODS: We submitted two groups of guinea pigs previously implanted with an electrode in the round window to a protocol of air diving in a hyperbaric chamber. Eardrums of animals in one of the two groups had been perforated beforehand. Twenty dives were practiced over 4 weeks. We chose dive parameters consistent with common sport diving: maximal pressure of 4 atmosphere absolute and duration of 30 minutes. Auditory threshold and cochlear spontaneous activity were recorded at regular intervals. Furthermore, we recorded spontaneous cochlear activity in Heliox 400-m and 600-m dives to determine whether our conclusions hold for "extreme" diving. RESULTS: In the group with perforated eardrums, no variation of those parameters were recorded, even in extreme diving. Important variations were noticed in the other group. CONCLUSIONS: Pressure applied directly on the inner ear during diving does not disturb cochlear activity.

Animals↗

Contrast enhanced color Doppler endorectal sonography of prostate: efficiency for detecting peripheral zone tumors and role for biopsy procedure.

PURPOSE: We evaluated the accuracy of contrast enhanced color Doppler endorectal ultrasound to guide biopsy for the detection of prostate cancer. MATERIALS AND METHODS: A total of 85 patients were evaluated with gray scale and color Doppler before and during intravenous injection of ultrasound contrast agent made of galactose based air microbubbles. Our biopsy protocol was performed during contrast injection. An additional 18 directed cores were obtained based on contrast enhanced imaging. Diagnostic efficiency with and without contrast medium injection for detecting prostate cancer were compared based on biopsy results. RESULTS: Cancer was identified in a total of 58 biopsy sites in 54 patients. Gray scale imaging revealed 96 abnormal hypoechoic nodules or irregular zones inside the outer gland, of which 48 were malignant on pathological evaluation. Contrast enhanced color Doppler had higher sensitivity (93%) than unenhanced color Doppler (54%), while specificity increased only 79% to 87% for enhanced imaging. Nine of 10 isoechoic suspicious zones were depicted with enhancement, while unenhanced Doppler detected 7 of them. There was no significant difference between the intensity of enhancement and tumor Gleason scores. CONCLUSIONS: Contrast enhanced color Doppler endorectal sonography increases the detection of prostate cancer. Improvement in sensitivity was high, while the difference in specificity was not as pertinent. It is accurate when using a common and routine application ultrasound unit. This technique is easy to perform and not time-consuming. Obtaining additional biopsy cores of suspicious enhancing foci significantly improves the detection rate of cancer.

Aged↗

Pulse-inversion harmonic imaging improves lesion conspicuity during US-guided biopsy.

PURPOSE: To assess the feasibility of percutaneous biopsy of low-conspicuity focal liver lesions with use of pulse-inversion harmonic imaging (PIHI) guidance in the late phase after injection of microbubble contrast agent. MATERIALS AND METHODS: Twelve patients referred for ultrasound (US)-guided biopsy had liver lesions lacking adequate conspicuity to undergo biopsy under conventional ultrasound (US) guidance. They underwent biopsy procedures performed with the use of PIHI guidance in the late phase after injection of Levovist. The conspicuity of lesions, procedure time, number of passes, and success and complication rates were documented and compared to a control group. The control group consisted of retrospective analysis of 19 patients who had undergone conventional US-guided biopsy procedures performed by the same radiologist. RESULTS: After contrast material injection, all lesions had sufficient increases in conspicuity to be targeted under PIHI guidance. Procedure time was prolonged in the PIHI group (66 minutes; range, 30-120 min; vs control, 33 min; range, 15-77 min; P <.01, Wilcoxon signed-rank test). The number of passes was greater in the PIHI group (1.9 +/- 0.3; vs control, 1.4 +/- 0.6; P <.01, chi(2) test). No statistically significant difference was observed when comparing success and complication rates. CONCLUSION: PIHI in the late phase after injection of Levovist generated clear delineation of focal liver lesions in all cases, allowing an accurate and safe sampling. This technique broadens the scope of US-guided biopsy to lesions lacking adequate conspicuity on conventional US.

Adult↗

Cyclosporine A does not alter ultrasonic indices of renal blood flow: a potential tool for differentiating toxicity from acute rejection?

The narrow therapeutic window of cyclosporine A (CsA) means its use is controlled by pharmacokinetic monitoring. However, pharmacokinetics do not always reflect the functional effects of a drug--its pharmacodynamics, such as vasoconstriction. We developed a technique for measuring renal blood flow and used a pig model to determine whether CsA-induced renal vasoconstriction could be detected, thus offering a tool for pharmacodynamic therapeutic drug monitoring. This has been shown to differentiate acute rejection from acute tubular necrosis. Power Doppler intensitometry was used to assess relative vascular volume, and the renal arteriovenous transit time was determined with an intravenous microbubble bolus. Measurements were taken before and at intervals after an intravenous bolus of CsA (10 mg/kg). There was no correlation between index and CsA concentration. Lack of detectable effect after CsA administration to high concentrations suggests that this technique may be able to differentiate CsA toxicity from acute rejection.

Animals↗

Unstable diffusion and chemical dissociation of a single sonoluminescing bubble.

In a certain parameter region, a single sonoluminescencing bubble is unstable against diffusion of gases and their chemical dissociation. Experiments show that a surface unstable bubble emits a microbubble and recoils. After this it exhibits specific dynamical features whereby the ambient radius changes in a nonmonotonic way. A numerical analysis identifies the phenomenon as the result of the interplay between spatial translations and induced variations of driving pressure on one side and the chemical composition of gases in the bubble on the other side. The results confirm that dynamical chemical dissociation phenomena as well as acoustic properties play an important role in the understanding of single-bubble sonoluminescence.

Journal Article↗

Viscosity destabilizes sonoluminescing bubbles.

In single-bubble sonoluminescence (SBSL) microbubbles are trapped in a standing sound wave, typically in water or water-glycerol mixtures. However, in viscous liquids such as glycol, methylformamide, or sulphuric acid it is not possible to trap the bubble in a stable position. This is very peculiar as larger viscosity normally stabilizes the dynamics. Suslick and co-workers call this new mysterious state of SBSL "moving-SBSL." We identify the history force (a force nonlocal in time) as the origin of this destabilization and show that the instability is parametric. A force balance model quantitatively accounts for the observed quasiperiodic bubble trajectories.

Journal Article↗

Enhancement of contrast echocardiography by image variability analysis.

BACKGROUND: Although there have been recent advances in echocardiography, many studies remain suboptimal due to poor image quality and unclear blood-myocardium border. We developed a novel image processing technique, cardiac variability imaging (CVI), based on the variance of pixel intensity values during passage of ultrasound microbubble contrast into the left ventricle chamber, with the aim of enhancing endocardial border delineation and image quality. METHODS AND RESULTS: CVI analysis was performed on simulated data to test and verify the mechanism of image enhancement. Then CVI analysis was applied to echocardiographic images obtained in two different clinical studies, and still images were interpreted by expert reviewers. In the first study (N = 15), using contrast agent EchoGen, the number of observable wall segments in end-diastolic images, for example, was significantly increased by CVI (4.93) as compared to precontrast (3.28) and contrast images (3.36), P < 0.001 for both comparisons to CVI. In the second study (N = 8), using contrast agent Optison, interobserver variability of manually traced end-diastolic volumes was significantly decreased using CVI (22.3 ml) as compared to precontrast (63.4) and contrast images (49.0), P < 0.01 for both comparisons to CVI. CONCLUSION: CVI can substantially enhance endocardial border delineation and improve echocardiographic image quality and image interpretation.

Algorithms↗

Shell waves and acoustic scattering from ultrasound contrast agents.

Ultrasound contrast agents are encapsulated microbubbles, filled either with air or a higher weight molecular gas, ranging in size from 1 to 10 microns in diameter. The agents are modeled as air-filled spherical elastic shells of variable thickness and material properties. The scattered acoustic field is computed from a modal series solution, and reflectivity and angular scattering are then determined from the computed fields for agents of various properties. We show that contrast agents also support shell resonance responses in addition to the monopole response, which has been the focus of previous contrast agent studies. Lamb waves appear to be the source of these additional responses. A shell or curvature Lamb wave generates dipole peaks in the 1- to 40-MHz range for 2.5 to 3.5 microns radius agents with elastic properties approximating those of albumin protein. The inclusion of damping affects the lower frequency dipole peaks but is less important for responses occurring above approximately 30 MHz. Moreover, these responses hold untapped potential for clinical ultrasound applications such as tissue perfusion studies and high frequency contrast agent imaging.

Biomedical Engineering↗

Acoustic activation of targeted liquid perfluorocarbon nanoparticles does not compromise endothelial integrity.

Perfluorocarbon nanoparticles consisting essentially of liquid perfluoro-octyl bromide (PFOB) core surrounded by a lipid monolayer can serve as highly specific site-targeted contrast and therapeutic agents after binding to cellular biomarkers. Based on previous findings that ultrasound applied at 2 MHz and 1.9 mechanical index (MI) for a 5-min duration dramatically enhances the cellular interaction of targeted PFOB nanoparticles with melanoma cells in vitro without inducing apoptosis or other harmful effects to cells that are targeted, we sought to define mechanisms of interaction and the safety profile of ultrasound used in conjunction with liquid perfluorocarbon nanoparticles for targeted drug delivery, as compared with conventional microbubble ultrasound contrast agents under identical insonification conditions. Cell-culture inserts were used to grow a confluent monolayer of human umbilical vein endothelial cells. Definity in conjunction with continuous wave ultrasound (2.25 MHz for 1 and 5 min) increased the permeability of monolayer by four to six times above the normal, decreased transendothelial electrical resistance (a sign of reduced membrane integrity), and decreased cell viability by approximately 50%. Histological evaluation demonstrated extensive disruptions of cell monolayers. Nanoparticles (both nontargeted and targeted) elicited no changes in these different measures under similar insonification conditions and did not disrupt cell monolayers. We hypothesize that ultrasound facilitates drug transport from the perfluorocarbon nanoparticles not by cavitation-induced effects on cell membrane but rather by direct interaction with the nanoparticles that stimulate lipid exchange and drug delivery.

Acoustics↗

Optical and acoustical interrogation of submicron contrast agents.

Unlike conventional ultrasound contrast agents with a diameter of several microns, in this paper we explore the use of submicron contrast agents for the detection and localization of lymph nodes. The submicron agents are gas-filled, double-walled microspheres that rupture when exposed to ultrasound energy at megahertz frequencies. In this study, three experimental systems are combined with model predictions to assist in understanding the response of these unique agents to a range of signal transmission parameters. Optical experimental results for each agent delineate the relative expansion as a function of acoustical peak negative pressure, pulse length, and center frequency. The optical images demonstrate an order of magnitude expansion in radius during the pulse rarefaction, in which the expansion magnitude is dependent on the transmitted pressure and frequency. Simulations using a modified Rayleigh-Plesset model predict an increasing relative expansion for the microbubbles (initial bubble radius ranging from 0.3-1.3 microm) with increasing pressure and decreasing initial radius. Acoustically recorded frequency spectra reveal the presence of harmonics for a range of transmitted pulses. In addition, in-vivo results from a normal canine model demonstrate marked contrast enhancement of first order lymph nodes. We hope to offer an alternative to present intra-operative procedures for sentinel node detection.

Animals↗

A novel sensor for monitoring acoustic cavitation. Part I: Concept, theory, and prototype development.

This paper describes a new concept for an ultrasonic cavitation sensor designed specifically for monitoring acoustic emissions generated by small microbubbles when driven by an applied acoustic field. Its novel features include a hollow, open-ended, cylindrical shape, with the sensor being a right circular cylinder of height 32 mm and external diameter 38 mm. The internal diameter of the sensor is 30 mm; its inner surface is fabricated from a 110-microm layer of piezoelectrically active film whose measurement bandwidth is sufficient to enable acoustic emissions up to and beyond 10 MHz to be monitored. When in use, the sensor is immersed within the liquid test medium and high frequency (megahertz) acoustic emissions occurring within the hollow body of the sensor are monitored. In order to shield the sensor response from events occurring outside the cylinder, the outer surface of the sensor cylinder is encapsulated within a special 4-mm thick polyurethane-based cavitation shield with acoustic properties specifically developed to be minimally perturbing to the 40 kHz applied acoustic field but attenuating to ultrasound generated at megahertz frequencies (plane-wave transmission loss > 30 dB at 1 MHz). This paper introduces the rationale behind the new sensor, describing details of its construction and the materials formulation program undertaken to develop the cavitation shield.

Journal Article↗