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 Sonoelasticity of organs: shear waves ring a bell.
Author Parker KJ, Lerner RM.
Journal J Ultrasound Med
Volume
Year 1992
Abstract Sonoelasticity is the use of ultrasonography to visualize, in real time, the hardness of stiffness of.tissues and organs by depicting the tissue's motion in response to an applied vibration source..The applied vibration source is usually of low amplitude and low frequency (less than 0.1 mm.displacement and less than 2000 Hz). Under these conditions, the natural vibration response of.tissues and whole organs is revealed as a standing wave pattern determined by the low-frequency.elastic constants of the tissues and their boundary conditions, factors that are not related to the.ultrasonic echogenicity. As a result, hard or dense isoechoic tumors that are undetectable by.conventional ultrasonography often can be visualized in sonoelasticity imaging by virtue of their.altered vibration response. In this report, we demonstrate the appearance of organs such as the.breast, liver, and kidney during real-time, in vivo sonoelasticity imaging. The results show that.the shape and location of vibration patterns are dependent on the tissues and vibration.frequencies; thus, information about the basic elastic properties of tissues should be obtainable.


Title Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis).
Author Tarantal AF, Chu F, O'Brien WD Jr, Hendrickx AG.
Journal J Ultrasound Med
Volume
Year 1993
Abstract Temperature elevations that occur during diagnostic ultrasonic exposure were assessed in vivo in gravid macaques after 10, 20, or 30 min (scan mode; N = 30) or 5, 10, or 15 min (pulsed Doppler; N = 32). Five time points were assessed during the second and third trimesters (gestational days 70 to 150 +/- 2; term, approximately 165 days) using a transient thermocouple technique. Measurements were obtained intracranially or at the muscle-bone interface using a commercial sector scanner (ATL MK 600, 7.5 MHz scanhead; scan mode, ISPTA) = 27 mW/cm2, ISPPA = 85 W/cm2, pulse repetition frequency (PRF) = 1 kHz; pulsed Doppler - ISPTA = 54 mW/cm2, ISPPA = 1.5 W/cm2, PRF = 18.5 kHz). Overall, the greatest temperature elevation achieved with either modality or location was 0.6 degrees C.


Title Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis)/
Author Tarantal AF, Chu F, O'Brien WD Jr, Hendrickx AG.
Journal J Ultrasound Med
Volume
Year 1993
Abstract Temperature elevations that occur during diagnostic ultrasonic exposure were assessed in vivo in gravid macaques after 10, 20, or 30 min (scan mode; N = 30) or 5, 10, or 15 min (pulsed Doppler; N = 32). Five time points were assessed during the second and third trimesters (gestational days 70 to 150 +/- 2; term, approximately 165 days) using a transient thermocouple technique. Measurements were obtained intracranially or at the muscle-bone interface using a commercial sector scanner (ATL MK 600, 7.5 MHz scanhead; scan mode, ISPTA) = 27 mW/cm2, ISPPA = 85 W/cm2, pulse repetition frequency (PRF) = 1 kHz; pulsed Doppler - ISPTA = 54 mW/cm2, ISPPA = 1.5 W/cm2, PRF = 18.5 kHz). Overall, the greatest temperature elevation achieved with either modality or location was 0.6 degrees C.


Title Sonoluminescence.
Author Walton AJ, Reynolds GT.
Journal Adv Phys
Volume
Year 1984
Abstract Sonoluminescence (SL) is the name given to the light emitted when a liquid is cavitated in a particular (rather violent) manner. The appropriate cavitation conditions can be realized by using high intensity ultrasound, a spark discharge, a laser pulse, or by flowing the liquid through a Venturi tube. SL occurs in a wide variety of liquids, its intensity and spectrum depending on the nature of the solvent and the solute (including dissolved gas). The intensity, but apparently not the spectrum, also depends on the frequency of the sound and on the temperature and hydrostatic pressure of the liquid. In a standing wave sound field the SL originates from bubbles attracted to the pressure antinodes and has its maximum intensity when the bubble volume is a minimum. The phase of the sound cycle at which this occurs depends on the amplitude and frequency of the sound field. Spectral measurements show that SL originates mainly from the recombination of free radicals created within the high temperature and high pressure environment of a bubble undergoing an adiabatic compression, as may happen either during transient cavitation or during highly non-linear, but stable, cavitation. In discussing these, and other, attributes of SL this review emphasizes developments over the past 20 years. Because of the importance of the dynamical theory of bubbles to a full understanding of SL, it includes an account of bubble dynamics. In addition, it describes the various experimental techniques employed in the creation and analysis of SL. Although the review.lays particular stress on the SL produced via acoustic cavitation, it also examines the characteristics of the SL produced using other methods of cavitation.


Title Sonolysis of Albunex®-supplemented, 40% hematocrit human erythrocytes by pulsed 1-MHz ultrasound: Pulse number, pulse duration and exposure vessel rotation dependence.
Author Brayman AA, Miller MW.
Journal Ultrasound Med Biol
Volume
Year 1999
Abstract The hypotheses tested were that sonolysis of erythrocytes in the presence of a gas-based ultrasound contrast agent in vitro will be related quantitatively to the duration and number of ultrasound pulses applied using a constant pulse repetition period and, at least qualitatively, to the total exposure duration (i.e., the product of pulse number x pulse duration). An objective was to determine the influence of sample rotation during insonation on the amount of hemolysis produced under these conditions. Human erythrocytes, suspended to 40% hematocrit in autologous plasma containing 3.6% (V:V) Albunex®, were exposed/sham-exposed to 1-100 pulses of 1-MHz ultrasound (6.2 MPa peak positive, 3.6 MPa peak negative acoustic pressures; I(SPTP)~800 W/cm² using a 1-s pulse repetition period. Pulse durations ranged from 20-20,000 mu s; samples were either stationary or rotated (200 rpm) during insonation. Hemolysis was independent of vessel rotation treatment at all tested pulse durations and pulse numbers. Levels of hemolysis statistically greater than in sham-exposed samples were obtained with >or=50 pulses of 20 mu s duration, and >or=1 pulse of 200, 2000 or 20,000 mu s duration. Hemolysis increased with increasing pulse number and pulse duration. Approximately equivalent levels of hemolysis were produced by different pulse number x pulse duration combinations, yielding the same total exposure duration.


Title Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study.
Author Park D, Ryu H, Kim HS, Kim YS, Choi KS, Park H, Seo J.
Journal Ultrasound Med Biol
Volume
Year 2012
Abstract Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.


Title Sonophoresis. I. The use of high-frequency ultrasound to enhance transdermal drug delivery.
Author Bommannan D, Okuyama H, Stauffer P, Guy RH.
Journal Pharm Res
Volume
Year 1992
Abstract Previous attempts to use ultrasound (less than or equal to 1-MHz frequency and 1 to 3-W/cm2 intensity) to enhance transdermal drug delivery (so-called sonophoresis) have produced inconsistent results. Theoretical analysis of ultrasound propagation in tissue predicts that higher-frequency ultrasound (greater than 1 MHz) will increase the concentration of energy deposition in the stratum corneum (SC) (typically, the rate-limiting barrier to percutaneous penetration). This hypothesis was tested by comparing the passive transdermal delivery of salicylic acid with that under the influence of ultrasound at 2-, 10-, and 16-MHz frequency; measurements were performed in vivo in hairless guinea pigs. Total drug absorbed was quantified by determining the amount of salicylic acid (1) present in SC tape strips and (2) eliminated in urine. Sonophoresis for 20 min at 2 MHz caused no significant increase in salicylic acid delivery over passive diffusion; treatment with ultrasound at 10 and 16 MHz, on the other hand, significantly elevated salicylic acid transport, by 4-fold and 2.5-fold, respectively. Kinetic analysis of the sonophoretic data at 10 and 16 MHz also revealed that the diffusion lag time associated with transdermal drug delivery (TDD) was reduced. A shorter period (5 min) of sonophoresis again resulted in enhanced TDD (relative to the corresponding control) at the higher frequencies; the delivered dose, and the level of enhancement, however, were lower than those after the 20-min treatment. In a separate series of experiments, it was shown that (a) ultrasound did not alter the release kinetics of salicylic acid from the gel formulation used and (b) pretreatment of the skin with ultrasound at 10 and 16 MHz lowered skin barrier function such that subsequent delivery of salicylic acid was enhanced compared to passive transport without sonophoresis pretreatment. It follows that the enhancing effect of sonophoresis is due to a direct effect of ultrasound on (presumably) the stratum corneum.


Title Sonoporation of cultured cells in the rotating tube exposure system.
Author Miller DL, Bao S, Morris JE.
Journal Ultrasound Med Biol
Volume
Year 1999
Abstract Suspensions of Chinese hamster ovary cells were exposed to ultrasound in the presence of fluorescent dextran to determine the conditions needed for sonoporation with uptake of the large molecules. Albunex(r), a gas-body-based ultrasound contrast agent, was added to enhance cavitation. Ultrasound was continuous wave at frequencies of 1.0, 1.68, 2.25, 3.3, 5.3, and 7.15 MHz. Sterile 4.5-mL exposure chambers were rotated at 60 rpm to promote cavitation activity during the 1-min exposures. After exposure, cells were tested for sonoporation by counting fluorescent cells and for cell lysis by counting cells stained by trypan blue. Sonoporation was a sensitive bioeffects indicator that was detected at pressure amplitudes lower than were needed for transient cavitation or cavitation-induced cell lysis. For 10% Albunex, apparent thresholds for sonoporation, which were comparable to the levels required to perturb the gas bodies, were 0.084 MPa (spatial peak negative pressure amplitude) from 1.0-3.3 MHz and 0.27 MPa at 5.3 and 7.15 MHz, Sonoporation decreased slightly if the tube was not rotated. The effects increased for increasing Albunex concentration (with rotation). The plating efficiency of cells exposed to 0.2 MPa at 2.25 MHz and sorted by a flow cytometer was 19% (3.6% standard deviation SD) for fluorescent cells, compared to 67% (1% SD) for nonfluorescent exposed cells and 62% (6% SD) for sham-exposed cells. The reduced viability represents an important consideration for possible applications of sonoporation.


Title Sonoporation of the minicircle-VEGF165 for wound healing of diabetic mice.
Author Yoon CS,Jung HS,Kwon MJ,Lee SH,Kim CW,Kim MK,Lee M,Park JH.
Journal Pharm Res
Volume
Year 2009
Abstract Purpose: The purpose of this study is to examine the efficiency of sonoporation with minicircle DNA for the skin wound healing in diabetic mice. Methods: Minicircle DNA containing the human VEGF165 was constructed and tested in vitro. Diabetes was induced in 2-week old male C57BL/6J mice via streptozotocin (STZ) injection. 6 mm circular skin wounds were made on the mice back. After the subcutaneous injection of the minicircle DNA at the edge of the wound, the mice were exposed to the ultrasound irradiation for the sonoporation. Wound areas were analyzed until the day 12. Blood perfusion and angiogenesis were evaluated using a laser Doppler imaging and CD31 immunostaining, respectively. Re-epithelialization was assessed by histochemical analysis using hematoxylin and eosin staining. Results: Accelerated wound closure was observed in the mice receiving sonoporation of minicircle-VEGF165, which corresponds to the markedly increased skin blood perfusion and CD31 expression. Histological analysis revealed that the minicircle treated wound tissues showed fully restored normal architectures as compared with the non-treated diabetic controls with the markedly edematous and chaotic morphologies. Conclusions: Ultrasound mediated gene therapy with the minicircle-VEGF165 is effective for the healing of the skin wound of the diabetic mice. KEY WORDS diabetic mice - gene delivery - minicircle - sonoporation - wound healing


Title Sonoporation.
Author Forbes MM. O'brien WD,Jr.
Journal Ultrasonics
Volume
Year 2007
Abstract Sonoporation utilizes the interaction of ultrasound (US) with ultrasound contrast agents (UCAs)to temporally permeabilize the membrane of cells allowing for the uptake of DNA and drugs. This membrane alteration is transient, leaving the compounds trapped inside the cell after US exposure. Small compounds, macromolecules, DNA, and other therapeutic compounds have been delivered into cells using US with UCAs. US with UCAs can also deliver protein and DNA into tissues. Low- and high-frequency US treatment of cells in the presence of plasmid DNA has been shown to cause cell transfection in vitro and in vivo. Thus, sonoporation has great possibilities in both targeted drug delivery and gene therapy. Little is known about the mechanism of sonoporation both physically and biologically, and until the mechanism(s) is(are) identified, optimal sonoporation effect will be left to trial and error. The presence of UCAs is necessary to induce a significant sonoporation event. This UCA requirement has led to the identification of various bubble-associated phenomena (shear stress, microjetting, inertial cavitation,etc.) as possible mechanism(s). However, these data provide only circumstantial, not direct, evidence about sonoporation mechanisms. Sonoporation has significant advantages for therapy, notably the ability for its spatial and temporal control, and thus a better understanding of its mechanism(s) could hasten its clinical acceptance.


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