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 Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells.
Author Forbes MM, Steinberg RL, O'Brien WD Jr.
Journal J Ultrasound Med
Volume
Year 2010
Abstract OBJECTIVES: Sonoporation uses ultrasound (US) and ultrasound contrast agents (UCAs) to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds non-invasively into specific target cells. The objective of this study was to elucidate the biophysical mechanism of sonoporation, specifically the role of UCAs as well as exposure frequency. The inertial cavitation (IC) thresholds of the lipid-shelled octafluoropropane UCA were directly compared to the levels of generated sonoporation to determine the involvement of UCAs in producing sonoporation. METHODS: Chinese hamster ovary cells were exposed as a monolayer in a solution of the UCA, 500,000-Da fluorescein isothiocyanate-dextran, and phosphate-buffered saline to 30 seconds of pulsed US (pulse duration, 5 cycles; pulse repetition frequency, 10 Hz) at 3 frequencies (0.92, 3.2, and 5.6 MHz). The peak rarefactional pressure (P(r)) was varied over a range from 4 kPa to 4.1 MPa, and 5 to 7 independent replicates were performed at each pressure. RESULTS: The experimental observations demonstrated that IC was likely not the physical mechanism for sonoporation. Sonoporation activity was observed at pressure levels below the threshold for IC of the UCA (1.27 ± 0.32 MPa at 0.92 MHz, 0.84 ± 0.19 MPa at 3.2 MHz, and 2.57 ± 0.26 MPa at 5.6 MHz) for all 3 frequencies examined. The P(r) values at which the peak sonoporation activity occurred were 1.4 MPa at 0.92 MHz, 0.25 MPa at 3.2 MHz, and 2.3 MPa at 5.6 MHz. The UCA collapse thresholds followed a similar trend. A 1-way analysis of variance test confirmed that sonoporation activity differed among the 3 frequencies examined (P = 10(-8)). CONCLUSIONS: These results thus suggest that sonoporation is related to linear and/or nonlinear oscillation of the UCA occurring at pressure levels below the IC threshold.


Title Frequency-dependent evaluation of the role of definity in producing sonoporation of Chinese hamster ovary cells.
Author Forbes MM, Steinberg RL, O'Brien WD Jr.
Journal J Ultrasound Med
Volume
Year 2011
Abstract OBJECTIVES: Sonoporation uses ultrasound (US) and ultrasound contrast agents (UCAs) to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds non-invasively into specific target cells. The objective of this study was to elucidate the biophysical mechanism of sonoporation, specifically the role of UCAs as well as exposure frequency. The inertial cavitation (IC) thresholds of the lipid-shelled octafluoropropane UCA were directly compared to the levels of generated sonoporation to determine the involvement of UCAs in producing sonoporation. METHODS: Chinese hamster ovary cells were exposed as a monolayer in a solution of the UCA, 500,000-Da fluorescein isothiocyanate-dextran, and phosphate-buffered saline to 30 seconds of pulsed US (pulse duration, 5 cycles; pulse repetition frequency, 10 Hz) at 3 frequencies (0.92, 3.2, and 5.6 MHz). The peak rarefactional pressure (P(r)) was varied over a range from 4 kPa to 4.1 MPa, and 5 to 7 independent replicates were performed at each pressure. RESULTS: The experimental observations demonstrated that IC was likely not the physical mechanism for sonoporation. Sonoporation activity was observed at pressure levels below the threshold for IC of the UCA (1.27 ± 0.32 MPa at 0.92 MHz, 0.84 ± 0.19 MPa at 3.2 MHz, and 2.57 ± 0.26 MPa at 5.6 MHz) for all 3 frequencies examined. The P(r) values at which the peak sonoporation activity occurred were 1.4 MPa at 0.92 MHz, 0.25 MPa at 3.2 MHz, and 2.3 MPa at 5.6 MHz. The UCA collapse thresholds followed a similar trend. A 1-way analysis of variance test confirmed that sonoporation activity differed among the 3 frequencies examined (P = 10(-8)). CONCLUSIONS: These results thus suggest that sonoporation is related to linear and/or nonlinear oscillation of the UCA occurring at pressure levels below the IC threshold.


Title Frequent prenatal ultrasound: time to think again.
Author Keirse MJ.
Journal Lancet
Volume
Year 1993
Abstract No abstract available.


Title Full-wave modeling of therapeutic ultrasound: nonlinear ultrasound propagation in ideal fluids.
Author Ginter S, Liebler M, Steiger E, Dreyer T, Riedlinger RE.
Journal J Acoust Soc Am
Volume
Year 2002
Abstract The number of applications of high-intense, focused ultrasound for therapeutic purposes is growing. Besides established applications like lithotripsy, new applications like ultrasound in orthopedics or for the treatment of tumors arise. Therefore, new devices have to be developed which provide pressure waveforms and distributions in the focal zone specifically for the application. In this paper, a nonlinear full-wave simulation model is presented which predicts the therapeutically important characteristics of the generated ultrasound field for a given transducer and initial pressure signal. A nonlinear acoustic approximation in conservation form of the original hydrodynamic equations for ideal fluids rather than a wave equation provides the base for the nonlinear model. The equations are implemented with an explicit high-order finite-difference time-domain algorithm. The necessary coefficients are derived according to the dispersion relation preserving method. Simulation results are presented for two different therapeutic transducers: a self-focusing piezoelectric and one with reflector focusing. The computational results are validated by comparison with analytical solutions and measurements. An agreement of about 10% is observed between the simulation and experimental results.


Title Functional changes in white blood cells after microsonation.
Author Crowell JA, Kusserow BK, Nyborg WL.
Journal Ultrasound Med Biol
Volume
Year 1977
Abstract White-cell-rich canine plasma was subjected to the field of a microvibrator at 20 kHz, in order to obtain information on the vulnerability of blood elements to ultrasonically produced shearing stresses. Destruction of the white cells occurs at amplitudes above a critical threshold value; the latter is less than the corresponding threshold for red cells. Functional characteristics, measured by indices of phagocytic, bacteriocidal, and metabolic activities, are altered at amplitudes much lower than the critical value for cell destruction. The results have implications for possible bio-effects in ultrasonic fields when gaseous pockets or bubbles of optimum size are present.


Title Functional effects of focused ultrasound on mammalian nerves.
Author Young RR, Henneman E.
Journal Science
Volume
Year 1961
Abstract Differential blocking of conduction in mammalian nerve fibers has been produced by irradiation of the whole nerve with focused ultrasound. The smallest (C) fibers are the most sensitive; the largest (A-alpha) fibers are the least vulnerable. Fully reversible blocking can be obtained with carefully graded doses of ultrasound.


Title Functional neoangiogenesis imaging of genetically engineered mouse prostate cancer using three-dimensional power doppler ultrasound.
Author Xuan JW, Bygrave M, Jiang H, Valiyeva F, Dunmore-Buyze J, Holdsworth DW, Izawa JI, Bauman G, Moussa M, Winter SF, Greenberg NM, Chin JL, Drangova M, Fenster A, Lacefield JC.
Journal Cancer Res
Volume
Year 2007
Abstract We report the first application of high-frequency three-dimensional power Doppler ultrasound imaging in a genetically engineered mouse (GEM) prostate cancer model. We show that the technology sensitively and specifically depicts functional neoangiogenic blood flow because little or no flow is measurable in normal prostate tissue or tumors smaller than 2-3 mm diameter, the neoangiogenesis "switch-on" size. Vascular structures depicted by power Doppler were verified using Microfil-enhanced micro-computed tomography (micro-CT) and by correlation with microvessel distributions measured by immunohistochemistry and enhanced vascularity visualized by confocal microscopy in two GEM models [transgenic adenocarcinoma of the mouse prostate (TRAMP) and PSP94 gene-directed transgenic mouse adenocarcinoma of the prostate (PSP-TGMAP)]. Four distinct phases of neoangiogenesis in cancer development were observed, specifically, (a) an early latent phase; (b) establishment of a peripheral capsular vascular structure as a neoangiogenesis initiation site; (c) a peak in tumor vascularity that occurs before aggressive tumor growth; and (d) rapid tumor growth accompanied by decreasing vascularity. Microsurgical interventions mimicking local delivery of antiangiogenesis drugs were done by ligating arteries upstream from feeder vessels branching to the prostate. Microsurgery produced an immediate reduction of tumor blood flow, and flow remained low from 1 h to 2 weeks or longer after treatment. Power Doppler, in conjunction with micro-CT, showed that the tumors recruit secondary blood supplies from nearby vessels, which likely accounts for the continued growth of the tumors after surgery. The microsurgical model represents an advanced angiogenic prostate cancer stage in GEM mice corresponding to clinically defined hormone-refractory prostate cancer. Three-dimensional power Doppler imaging is completely noninvasive and will facilitate basic and preclinical research on neoangiogenesis in live animal models.


Title Fundamental neurological research and human neurosurgery using intense ultrasound.
Author Fry WJ, Fry FJ.
Journal IRE Trans Med Electron
Volume
Year 1960
Abstract Focused high intensity ultrasound can be used, under accurately controlled dosage conditions, to produce either temporary or permanent changes in practically any desired brain structure. Volumes of tissue smaller than one tenth of a cubic millimeter can be affected in deep brain structures of experimental animals (cats and monkeys), and regions as large as desired can be changed by moving the focal spot of the ultrasonic beams through an appropriately chosen path. The changes can be induced without adversely affecting intervening brain structure and without interrupting the vascular system even within the site in which irreversible or permanent changes in the neural components are produced. The selectivity and absence of effects on the intervening tissue make focused ultrasound a tool of considerable power for investigating basic brain mechanisms. It is now being used in an extensive experimental animal program involving neuroanatomical, behavioral and physiological studies. It is also being used to study and modify the symptoms of various neurological disorders in humans. The signs and symptoms which have been and are under investigations in human patients at the present time include abnormal movements (tremor and nonpatterned), muscular rigidity), intractable pain (following amputations, cerebral vascular accidents, the acute phase of herpes zoster) and hypersensitivity to stimulation of the body surface. This paper includes brief descriptions of the instrumentation which has been developed for this type of fundamental neurological research and medical applications, the techniques of preparation and irradiation of the experimental animal and human patient, the types of research results which are obtained from experimental animal studies in which the ultrasonic dosage parameters are chosen for producing either irreversible or reversible changes, the results obtained from producing arrays of ultrasonic lesions in deep brain structures of patients suffering from various neurological disorders, and the present status of investigations of the physical mechanism of the action of the intense sound on the tissue.


Title Further examination of the effects of ultrasonic activation of gas bodies in Elodea leaves.
Author Miller DL.
Journal Environ Exp Bot
Volume
Year 1983
Abstract The effects of 5.25 MHz ultrasound on the intracellular organization of Elodea anacharis leaf cells were examined. Two types of disrupted cells, in which the cytoplasm and vacuolar contents were mixed, could be discerned; type I cells which take up vital stain immediately and type II cells in which organelles are displaced by centrifugation. The second type apparently involves a less severe, but still lethal, form of damage and leads to stain uptake (an indication of cell death) within 2 hr. Both focused and unfocused exposures began to cause these effects at a spatial-peak intensity of about 0.35 W/cm2 as the ultrasonic power was raised, but the broader beam affected many more cells. Young, mature and old leaves were affected equally by the ultrasound, but young leaves had a much higher proportion of type II disrupted cells 10 min after exposure than did old leaves.


Title Further investigations of ATP release from human erythrocytes exposed to ultrasonically activated gas-filled pores.
Author Miller DL, Williams AR.
Journal Ultrasound Med Biol
Volume
Year 1983
Abstract Suspensions of human erythrocytes in a firefly-extract solution were exposed to 2.0 MHz ultrasound in the presence of 3.4 microns dia. gas-filled pores. Lysis of the cells during ultrasonic exposure resulted in the release of ATP which produced light upon interaction with the firefly extract. The response was approximately proportional to the square of the SPTA intensity I for both continuous and pulsed exposures (1 mu s pulses, 1:9 duty cycle) within the range 5-100 mW/cm2. One method of graphical data presentation yielded an apparent threshold for the.effect at 0.31 bar pressure amplitude; however, a response could probably be obtained at any nonzero exposure level with a sufficiently sensitive apparatus. The response was also proportional to the exposure duration t for the range 0.03-3 s. The product I2 t may have some significance as a dosage parameter for this system in an, as yet, undefined "low-dose" range. Measurements for exposures with higher intensities, longer durations, lower duty factors and with pulses longer than 300 mu s deviated from these trends.


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