Bioacoustics Research Lab
University of Illinois at Urbana-Champaign | Department of Electrical and Computer Engineering | Department of Bioengineering
Department of Statistics | Coordinated Science Laboratory | Beckman Institute | Food Science and Human Nutrition | Division of Nutritional Sciences | College of Engineering
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William D. O'Brien, Jr. publications:

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Title Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von willebrand factor in hypercholesterolemic rabbits.
Author Smith BW, Simpson DG, Sarwate S, Miller RJ, Blue JP, Haak A, O'Brien WD Jr, Erdman J Jr.
Journal J Ultrasound Med
Volume
Year 2012
Abstract Objectives—Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Methods—Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. Results—After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; Padj < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Conclusions—Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.


Title Contrast ultrasound imaging of the aorta does not affect progression of atherosclerosis or cardiovascular biomarkers in ApoE(^-/-) mice
Author Smith BW, Simpson DG, Sarwate S, Miller RJ, Erdman JW Jr, O'Brien WD Jr.
Journal J Ultrasound Med
Volume
Year 2015
Abstract Objectives—Ultrasound contrast agents (UCAs) enhance cardiovascular ultrasound imaging. Adverse biological effects have occurred after administration of UCAs, and more research is needed for a comprehensive understanding of the risks involved. We used the ApoE–/– mouse model of atherosclerosis to characterize the effects of ultrasound and UCAs on atherosclerosis and plasma biomarkers. Methods—Male ApoE–/– mice (8 weeks old; n = 24) were intravenously infused with a UCA (2 × 1010 Definity microbubbles per hour; Lantheus Medical Imaging, North Billerica, MA) and exposed to 2.8-MHz center frequency ultrasound (10 Hz pulse repetition frequency, 1.4 microseconds pulse duration, 2 minutes exposure duration, and 2 sites) at 1 of 3 derated peak rarefactional pressure amplitudes (0, 1.9, or 3.8 MPa), and then consumed either a chow or Western diet for 4 weeks (n = 4 per group). Blood plasma samples were collected before ultrasound exposure and at 2 and 4 weeks after exposure and assayed for total cholesterol and von Willebrand Factor (vWF). A pathologist measured atheroma thickness in formalin-fixed, hematoxylin-eosin-stained transverse aorta sections and scored them for severity of atherosclerosis. Results—Plasma total cholesterol initially averaged 286 mg/dL in the Western diet group and increased to 861 mg/dL after 4 weeks on the diet (P < .0001). Total cholesterol did not increase significantly in the chow diet group. Plasma vWF increased after 2 weeks on the Western diet (P < .0001). Atheroma thickness was greater in animals consuming the Western diet than in chow-fed animals (P < .05). Ultrasound had no significant effect on plasma total cholesterol, plasma vWF, or atheroma thickness. Conclusions—Contrast ultrasound did not increase the severity of atherosclerosis or alter cardiovascular biomarkers in the ApoE–/– mouse model. Key Words—atherosclerosis; biomarkers; cardiovascular disease; contrast agents; endothelium; microbubbles; ultrasound


Title Contrast-enhanced transrectal ultrasonography of a novel canine prostate cancer model
Author Forsberg F, Johnson DK, Merton DA, Li JB, Losco PE, Hagen EK, Goldberg BB.
Journal J Ultrasound Med
Volume
Year 2002
Abstract OBJECTIVE: This study evaluated the utility of a new animal model for prostate cancer imaging using a new ultrasonographic contrast agent (Sonazoid [NC100100]; Amersham Health, Oslo, Norway), for prostate cancer detection. METHODS: Twenty-four dogs had a canine transmissible venereal sarcoma cell line injected (50 million cells/mL) directly into the prostate, producing a neoplasm in 15 to 40 days. Transrectal ultrasonography was performed in power Doppler mode on 8 dogs (phase I) and in gray scale phase inversion harmonic imaging mode on 16 animals (including control animals without tumors; phase II). Evaluations were repeated after intravenous injections of the contrast agent (dose, 0.00625-0.20 microL/kg). Histopathologic examination was performed after each study. For the phase II experiments, sensitivity, specificity, and accuracy were calculated. RESULTS: The contrast agent improved visualization of the prostate cancer vascularity and delineation of tumor size and shape in both power Doppler and phase inversion harmonic imaging modes. Canine transmissible venereal sarcoma tumors ranging from 3 x 5 to 40 x 50 mm were detected. The accuracy for detecting the number of prostate tumors increased (in phase II) from 67% to 87% with the addition of the contrast agent. Histopathologic examination confirmed the ultrasonographic findings and revealed typical canine transmissible venereal sarcoma cells infiltrating the prostate with moderate neovascularity. CONCLUSIONS: The novel canine tumor model was useful for evaluating ultrasonographic prostate imaging techniques. Improved detection of prostate tumors in dogs was possible with gray scale phase inversion harmonic imaging of the contrast agent. The accuracy of lesion detection increased from 67% to 87%.


Title Contribution to quantitative ultrasound diffraction tomography.
Author Duchene B, Lesselier D, Tabbara W.
Journal Proc Ultrason Symp IEEE
Volume
Year 1984
Abstract An experimental setup working at a frequency of 2 MHz has been used to evaluate the diffraction tomography method. Images of phantoms, such as nylon strings and natural rubber pipes, have been reconstructed using 8 views of the objects. The image is a map of the density of the induced sources in the object under investigation. An iterative method has been developed to extract from this density the values of C (speed of sound) and α (attenuation) in the phantom. Simulated results will be presented and discussed.


Title Contributions of mechanical and sonochemical effects to cell membrane damage induced by single-shot pulsed ultrasound with adjacent microbubbles.
Author Okada K,Kudo N,Kondo T,Yamamoto K.
Journal J Med Ultrasonics
Volume
Year 2008
Abstract Purpose. The objective was to investigate the contributions of mechanical effects due to kinetic force induced by the dynamic behavior of microbubbles and sonochemical effects due to free radicals produced by inertial cavitation to cell membrane damage under sonoporation conditions in which cells with adjacent microbubbles were irradiated with single-shot pulsed ultrasound. Methods. The free radical scavenger cysteamine was used to control the occurrence of sonochemical effects, and the ratios of cells with membrane damage to intact cells were compared in the presence and absence of cysteamine. To determine the optimal dose of cysteamine, free radical production on exposure to burst pulse ultrasound was investigated using KI-starch solutions with different concentrations (0–5 mM) of cysteamine. High-speed observation of the dynamic behavior of Levovist microbubbles during ultrasound exposure was also carried out in the presence and absence of cysteamine, and the difference in the ratios of the maximum bubble diameter to the initial diameter was evaluated. Next, human prostate cancer cells with adjacent Levovist microbubbles were exposed to single-shot pulsed ultrasound with a center frequency of 1 MHz, a peak negative pressure of 1.1 MPa, and a pulse width of 3 μs, and the percentages of cells with membrane damage were evaluated by fluorescent microscopy using propidium iodide in the presence and absence of cysteamine. Results. It was confirmed that cysteamine at a concentration of 5 mM completely suppressed sonochemical effects without causing a change in the dynamic response of microbubbles to pulsed ultrasound. The percentages of cells with membrane damage in the presence and absence of cysteamine (5 mM) were 10.3% ± 4.1% (n = 13) and 8.7% ± 3.9% (n = 9), respectively. No significant difference was found (P = 0.36). Conclusion. The results indicate that cell membrane damage induced by single-shot pulsed ultrasound with adjacent microbubbles was due mainly to mechanical effects, not to sonochemical effects. Keywords sonochemical effects - cell membrane damage - mechanism of sonoporation - single-shot pulsed ultrasound - ultrasound contrast agent


Title Control of splenic bleeding by using high intensity ultrasound.
Author Vaezy S, Martin R, Keilman G, Kaczkowski P, Chi E, Yazaji E, Caps M, Poliachik S, Carter S, Sharar S, Cornejo C, Crum L.
Journal J Trauma
Volume
Year 1999
Abstract BACKGROUND: High-intensity focused ultrasound (HIFU) has been shown to control bleeding from liver incisions, and blood vessel punctures and incisions. The objective of the current study was to investigate the capability of HIFU to stop bleeding from splenic injuries in a pig model. METHODS: Surgical incisions, 25 to 50 mm in length and 2 to 8 mm in depth, were made in the spleens of five anesthetized pigs. HIFU with a frequency of 5 MHz was applied within 5 seconds of making the incision. A total of 39 incisions and HIFU treatments were performed. RESULTS: Bleeding from all incisions was stopped completely after HIFU treatment. The average times to control and completely arrest the hemorrhage were 28 and 55 seconds, respectively. The mechanisms of hemostasis appeared to be thermally induced coagulation necrosis of splenic tissue and occlusion of blood vessels by a mechanically induced homogenized splenic tissue. CONCLUSION: HIFU may provide a useful method of hemostasis for actively bleeding spleen. Because of its ability to induce hemostasis at adjustable depth, HIFU may prove to be a useful cauterization method both in the operating room and for patients who are managed nonoperatively.


Title Controlled vesicle deformation and lysis by single oscillating bubbles.
Author Marmottant P,Hilgenfeldt S.
Journal Nature
Volume
Year 2003
Abstract The ability of collapsing (cavitating) bubbles to focus and concentrate energy, forces and stresses is at the root of phenomena such as cavitation damage, sonochemistry or sonoluminescence1, 2. In a biomedical context, ultrasound-driven microbubbles have been used to enhance contrast in ultrasonic images3. The observation of bubble-enhanced sonoporation4, 5, 6—acoustically induced rupture of membranes—has also opened up intriguing possibilities for the therapeutic application of sonoporation as an alternative to cell-wall permeation techniques such as electroporation7 and particle guns8. However, these pioneering experiments have not been able to pinpoint the mechanism by which the violently collapsing bubble opens pores or larger holes in membranes. Here we present an experiment in which gentle (linear) bubble oscillations are sufficient to achieve rupture of lipid membranes. In this regime, the bubble dynamics and the ensuing sonoporation can be accurately controlled. The use of microbubbles as focusing agents makes acoustics on the micrometre scale (microacoustics) a viable tool, with possible applications in cell manipulation and cell-wall permeation as well as in microfluidic devices.


Title Coronary vasolidation by noninvasive transcutaneous ultrasound an in vivo canine study.
Author Miyamoto T,Neuan Y,Luo H,Jeon D,Kobal S,Ikeno F,Horzewski M,Honda Y,Mirocha JM,Iwami T,Echt D,Fishbein MC,Siegel RJ.
Journal J Am Coll Cardiol
Volume
Year 2003
Abstract OBJECTIVES: We evaluated the coronary vasodilatory effects of transcutaneous low-frequency (27-kHz) ultrasound (USD). BACKGROUND: Ultrasound has been shown to affect vascular function. METHODS: Ultrasound energy was administered transcutaneously to 12 dogs. Coronary arterial dimensions were assessed using intravascular coronary ultrasound (IVUS) and quantitative coronary angiography (QCA). RESULTS: The IVUS mid-left anterior descending (LAD) luminal area was 6.77 ± 1.27 mm2 at baseline. After 30 s of ultrasound, this area increased by 9% (7.40 ± 1.44 mm2, p < 0.05), after 3 min by 19% (8.05 ± 1.72 mm2, p < 0.05) and after 5 min increased by 21% (8.16 ± 1.29 mm2, p < 0.05). The mean coronary diameter (2.69 ± 0.33 mm) at baseline (QCA of three segments of LAD and three segments of left circumflex coronary artery) increased by 19.3% (3.21 ± 0.28 mm) after 5 min of USD exposure. After a 90-min observation period there was a return to baseline values (p = NS). Intracoronary nitroglycerin (NTG) administered to five dogs revealed a similar magnitude of vasodilation as USD. CONCLUSIONS: Noninvasive, transthoracic low-frequency USD energy results in coronary artery vasodilation within seconds of exposure. The vasodilation is reversible and is similar in magnitude to that induced by NTG. Further evaluation is needed to assess its potential applications in humans.


Title Correcting for focusing when estimating attenuation for tissue characterization based on gaussian approximations of the beam profile.
Author Bigelow TA, McFarlin BL, O'Brien WD Jr.
Journal Proc Ultrason Symp IEEE
Volume
Year 2007
Abstract Abstract— Tissue attenuation has shown potential for characterizing soft tissues for many years, but natural biological variability has limited its effectiveness in many applications as a sole indicator of tissue health. Recently however, there has been increased interest in measuring tissue attenuation due to the need to compensate for frequency-dependent attenuation when quantifying scatterer correlation length and scatterer concentration. Correlation length and concentration might be capable of distinguishing benign from malignant tumors if attenuation can be accurately estimated. In this study, the traditional attenuation-estimation algorithm based on measuring the down-shift in center frequency of the ultrasound backscattered signal with propagation depth was modified to correct for focusing along the beam axis. Whereas previous approaches required a reference phantom to correct for the focusing, which is more challenging at higher frequencies, this approach corrected for the focusing by assuming that the field pattern along the focal zone could be approximated by a Gaussian function. Based on this approximation, a correction term was introduced to compensate for the effects of focusing when estimating attenuation in the focal region. The algorithm was verified using computer simulations and an ex vivo tissue sample, both of which used a 33-MHz spherically focused transducer with a focal length of 9 mm and an f-number of 3. The algorithm was validated in computer simulations by moving the region of interest used to obtain the attenuation through the focal region. The algorithms’ sensitivity to noise was also assessed by varying the frequency bandwidth used in the Gaussian fit to find the spectral-peak frequency from 15 to 50 MHz. The accuracy of the attenuation estimate in the computer simulations was on the order of 10% for all of the cases while the precision of the estimates varied from 5 to 35% depending on the available bandwidth. Similarly, the attenuation of the ex vivo tissue sample was 2.6±0.6 dB/cm-MHz using the developed algorithm compared to 2.5±0.4 dB/cm-MHz as measured using an insertion loss technique.


Title Correlation artifacts in speed of sound estimation in scattering media.
Author Ophir J, Johnson W, Yazdi Y, Shattuck D, Mehta D.
Journal Ultrasound Med Biol
Volume
Year 1989
Abstract A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated.by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of.arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are.a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report.computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the.properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the.second order statistical properties of the stairstep artifact are derived.


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