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Biomedical subjects

C C Church

Publications and source records attributed to C C Church.

17 recordsLinked to original sources

Acoustic cavitation produced by microsecond pulses of ultrasound: a discussion of some selected results.

Because of its extensive utilization in clinical practice, and because the subjects examined are often fragile and sensitive to trauma, the safety of diagnostic ultrasound has always been of concern. Of the various mechanisms through which ultrasound could act in a manner deleterious to a patient, acoustic cavitation, should it occur, appears to possess significant potential for biological damage. This paper reviews several recent reports of progress by our two groups and demonstrates the conditions under which cavitation has been observed by microsecond pulses of ultrasound. Although these results give no indications that diagnostic ultrasound may pose a true risk to a patient, they do indicate that in vivo cavitation may occur under certain conditions.

Animals

The acoustic filter: an ultrasonic blood filter for the heart-lung machine.

Cardiopulmonary bypass-associated encephalopathy is thought to be due in part to continuous microembolization of the brain with gas microbubbles more than 40 microns in diameter during bypass. Current barrier filter technology cannot effectively remove such small microbubbles in fragile fluids such as blood. The design concepts for a new nonbarrier ultrasound-based fluid filtration system (an "acoustic filter") capable of filtering small microbubbles from blood are presented. The acoustic filter uses a field of high-intensity ultrasound to push microbubbles down an acoustic gradient, where they can be collected and removed. To test the filtration efficiency of the system, a Doppler ultrasound bubble detector was built. By monitoring the prefilter and postfilter Doppler signal an assessment of filtration efficiency was made. A suspension of stable albumin-encapsulated microbubbles (4 to 32 microns) were used as a model of the microbubble contaminants that might be found in the arterial return line of the heart-lung machine. Inactivated, the acoustic filter neither removed nor added microbubbles to the fluid. Activated, the acoustic filter provided total or near-total clearing of microbubbles. We conclude that the acoustic filter can remove microbubbles from a cardiopulmonary bypass-like apparatus.

Acoustics

Time lapse and microscopic examinations of insonated in vitro cells.

A fibroblast cell line (Balb/c 3T3) was sham/exposed to ultrasound (2.2 MHz resonant frequency, 35.4 W/cm2 SPTP, 3 microseconds pulse duration, 200 Hz prf) for 30 min and subsequently scored for cell motility and alterations in cell morphology. Cell motility was assessed by computerized tracking of cells. Cell morphology ("normal" or "abnormal") was determined blindly by three independent scorers. A positive control (1-4 Gy) yielded statistically significant alterations in cell motility and morphology; no such differences were observed for the ultrasound regimen. The results thus fail to confirm an earlier report by Liebeskind et al. (Brit. J. Cancer 45(Suppl. V):176-186; 1982) of ultrasound-induced alterations in cell motility and morphology.

Animals

Confirmation of an ultrasound-induced mutation in two in-vitro mammalian cell lines.

In-vitro V79 and L5178Y cells were exposed in a rotating test tube to continuous-wave (CW) 1 MHz 35 W/cm2 ultrasound (0-4 or 0-3 min, respectively) and subsequently assayed for mutation as evidenced by resistance to 6-thioguanine (6-TG). There was a modest but statistically significant increase in mutation frequency in both cell types with increase in ultrasound exposure duration. X-ray exposures (3-9 Gy, a "positive control") yielded a large increase in 6-TG resistance. The data support an earlier report by Kaufman (1985) of an ultrasound-induced increase in mutation to 6-TG resistance in in-vitro mammalian cells.

Analysis of Variance

Confirmation of the protective effect of cysteamine in in vitro ultrasound exposures.

Armour and Corry (Radiat. Res. (1982) 89 369-380) reported that ultrasound-induced damage to in vitro Chinese hamster ovary cells was significantly reduced in the presence of cysteamine. The objective of this study was to attempt verification of this result. Four series of experiments were undertaken using in vitro cell suspensions, namely: (1) determination of the effect of cysteamine concentration on cell growth; (2) determination of the temperature dependence of ultrasonically induced cell damage; (3) determination of a dose-response relationship for the cytotoxicity of cysteamine; and (4) assessment of cell integrity and reproductive capacity in the presence or absence of cysteamine during ultrasonic exposure. Ultrasound parameters included a resonance frequency of 1 MHz, a continuous wave exposure duration of 5 min, and intensities from 0 to 21.6 W cm-2. The results indicated a dependence of ultrasound's efficacy on the medium's temperature during insonation and a significant reduction of ultrasound efficacy in compromising cellular integrity in the presence of cysteamine.

Animals

Sister chromatid exchanges in Chinese hamster ovary cells exposed to high intensity pulsed ultrasound: inability to confirm previous positive results.

This study was undertaken in an attempt to determine a physical mechanism of action for a recently published report of a small but statistically significant increase in sister chromatid exchanges (SCEs) in Chinese hamster ovary cells exposed to high-intensity pulsed ultrasound. The "positive" report's protocol involved a sizeable chance of ultrasound beam impingement on the side wall of the cell exposure chamber. Ten experiments per regimen were conducted; the regimens included exposures of (a) chamber center, (b) chamber wall, (c) nine grid sites, 0.5 mm between sites, and (d) nine grid sites, 1.5 mm between sites. The last was an exact replication of the conditions previously reported to induce the small SCE effect. The results did not support the postulate of an increase in SCEs with the ultrasound exposures.

Animals

An explanation for the decrease in cell lysis in a rotating tube with increasing ultrasound intensity.

Previous observations indicate that for in vitro mammalian cells insonated in rotating test tube the amount of cell lysis initially increases to some maximum and then decreases with further increase in ultrasound exposure. The results of the present investigation support the postulate that the reduction in cell lysis with increase in ultrasound intensity is related to the development of an ultrasonically induced "cloud" of bubbles in the fluid between the transducer and test tube; these bubbles mitigate against acoustic transmission thus reducing cell lysis in the insonated test tube.

Animals

A theoretical study of cavitation generated by an extracorporeal shock wave lithotripter.

The intense acoustic wave generated at the focus of an extracorporeal shock wave lithotripter is modeled as the impulse response of a parallel RLC circuit. The shock wave consists of a zero rise time positive spike that falls to 0 at 1 microsecond followed by a negative pressure component 6 microseconds long with amplitudes scaled to +1000 and -160 bars, P+ and P-, respectively. This pressure wave drives the Gilmore-Akulichev formulation for bubble dynamics; the zero-order effect of gas diffusion on bubble response is included. The negative pressure component of a 1000-bar shock wave will cause a preexisting bubble in the 1- to 10-microns range to expand to over 100 times its initial size, R0, for 250 microseconds, with a peak radius of approximately 1400 microns, then collapse very violently, emitting far UV or soft x-ray photons (black body). Gas diffusion does not appreciably mitigate the amplitude of the pressure wave radiated at the primary collapse, but does significantly reduce the collapse temperature. Diffusion also increases the bubble radius from R0 up to 40 microns and extends the duration of ringing following the primary collapse, assuming that the bubble does not break up or shed microbubbles. Results are sensitive to P+/P- and to the duration of the negative pressure cycle but not to rise time.

Lithotripsy

Lack of effect of continuous wave ultrasound exposure on in vivo Chinese hamster cheek pouch epithelial mitotic index.

Chinese hamster cheek pouches were everted and the epithelia exposed in vivo for 1 min to continuous wave 1.07 MHz ultrasound at intensities ranging from 0.5 to 10.0 W cm-2. Since the mitotic index of the hamster epithelium exhibited a circadian rhythm, the times of sonication and tissue sampling were arranged to allow for detection of a division delay as evidenced by a change in mitotic index in cells insonated in the early S or late S/early G2 phases of the cell cycle. There was no demonstrated effect of the ultrasound exposures on mitotic index.

Animals

Prediction of rectified diffusion during nonlinear bubble pulsations at biomedical frequencies.

A computer study of rectified diffusion was made over the biomedical frequency range (1-10 MHz). Solutions of the Gilmore-Akulichev [E. Cramer, in Cavitation and Inhomogeneities in Underwater Acoustics, edited by W. Lauterborn (Springer, New York, 1980), pp. 54-63] formulation for bubble dynamics were combined with the Eller-Flynn [A. Eller and H.G. Flynn, J. Acoust. Soc. Am. 37, 493-503 (1965)] approach to rectified diffusion in order to calculate thresholds and growth rates. It is found that: (1) for frequencies above 1 MHz, the widely held view that small bubbles grow by rectified diffusion to "resonance size" and then collapse violently is true only for narrow ranges of bubbles; (2) growth rates in the low megahertz range can be quite high for medically relevant pressures, approximately 20 micron/s at 1 MHz, 1 bar; (3) thresholds derived analytically are accurate for low frequencies over a wide range of bubble radii but, for high frequencies, only near the fundamental resonance radius; and (4) thresholds are quite sensitive to dissolved gas concentration at low frequencies.

Computer Simulation

A method to account for acoustic microstreaming when predicting bubble growth rates produced by rectified diffusion.

A reinterpretation of existing theory for rectified diffusion, the process by which bubbles in a sound field may grow in radius, is presented in order to quantitate the effect of acoustic microstreaming on bubble growth rates. The 1/t term in the growth rate equation is defined as the "decay term" and t as the "decay time," the time required for the gas concentration in the liquid contacting the bubble to rise (or fall) from its initial to its final value. In the absence of microstreaming, t is the duration of sonification. In the presence of microstreaming, t may be calculated from the streaming velocity and the bubble radius. A comparison between theory and the experimental results of Eller [A. Eller, J. Acoust. Soc. Am. 46, 1246-1250 (1969)] and of Gould [R.K. Gould, J. Acoust. Soc. Am. 56, 1740-1746 (1974)] shows reasonable agreement in the low kHz range. Theoretical results in the frequency range of 1-10 MHz at 1 and 4 bar are also presented.

Acoustics

Erratum: transient pulsations of small gas bubbles in water [J. Acoust. Soc. Am. 84, 985-998 (1988)] [corrected and republished].

Transient behavior of small gas bubbles in a liquid set into violent motion by ultrasonic pressure waves is of interest because of widespread use of microsecond pulses in diagnostic ultrasound. Such pulses contain only a few pressure cycles and the transient pulsations of bubbles set in motion by such pulses would determine the bubble-ultrasound interaction. A computer study has been made to obtain a global representation of the pulsation amplitudes R (t) of small gas bubbles (nuclei) in water during the first few cycles of a cw ultrasonic pressure. One objective was to obtain a better understanding of cavitation phenomena where many nuclei with initial radii Rn from 0.1-20 microns are set in motion at pressures ranging from 0.5-5 bars and at frequencies from 0.5-10 MHz. Results allowed construction of surfaces showing the relative bubble amplitude R/Rn as a function of Rn and of the time t/TA, where TA is the acoustic period. One finding is that, in the range of peak pressures found in diagnostic pulses, transient cavities would be generated during the first pressure cycle from nuclei with initial radii as small as a few microns (micron). Nuclei that grow into transient cavities in the first pressure cycle are here called "prompt" nuclei. At a specified pressure, the size range of radii Rn in which they occur decreases with increasing frequency. At 5 bars, the range of Rn for prompt nuclei is 0.166-11.35 microns at 0.5 MHz and vanishes at 10 MHz.

Gases

A mechanism for the generation of cavitation maxima by pulsed ultrasound.

A train of 1-MHz pulses can generate maxima of cavitation activity [V. Ciaravino, H. G. Flynn, and M. W. Miller, Ultrasound Med. Biol. 7, 159-166 (1981)] at pulse lengths of 6 and 60 ms and at pressure amplitudes, PA, between 5.4 and 9.4 bars (or intensities between 10 and 30 W/cm2). Generation of maxima at PA between these limits on pressure amplitude implies that the increase in cavitation activity originates from gas nuclei with radii lying in a critical size range centered at about 0.08 micron. The mechanism proposed for this phenomenon suggests that nuclei in this critical range are unstabilized nuclei generated in one pulse and surviving to the next with an appreciable fraction of the survivors lying in the critical range. Transient cavities that grow from such small nuclei are shown to behave as isolated mechanical systems that on reaching maximum size collapse as imploding spheres. The maximum pressures reached in such imploding cavities would then approximate those calculated for the spherical collapse of cavities. The occurrence of the observed maxima is ascribed to the spherical collapse of transient cavities.

Acoustics

Radiographic diagnosis of acute peroneal tendon dislocation.

Acute dislocation of the peroneal tendons at the ankle is accompanied, in a significant proportion of cases, by a characteristic small shelllike avulsion fracture of the lateral malleolus, rendering the lesion diagnosable radiographically. This small fracture is usually best seen on internal rotation oblique or occasionally on anteroposterior films of the ankle. It is seen as a bone flake only a few millimeters thick but often 1 cm or more in vertical diameter lying adjacent to the posterolateral surface of the lateral malleolus. It is an infrequent injury, now usually the result of a ski accident. Failure to recognize and treat the lesion can result in chronic disability.

Acute Disease

The kinetics and mechanics of ultrasonically-induced cell lysis produced by non-trapped bubbles in a rotating culture tube.

The kinetics of ultrasonically-induced cell lysis are examined in terms of classical radiation biology target theory. A theoretical expression relating the concentration of intact cells remaining after a given period of sonication in a rotating culture tube to the number of non-trapped bubbles, l, which a cell must encounter in order to be lysed is obtained. The expression is compared to experimental results in order to determine the actual value of l. It is found that l equals one (1). The concentration of non-trapped bubbles which is responsible for the observed cell lysis is calculated to be 250-500 cm-3. Finally, it is proposed that non-trapped bubbles tunnel into cells while undergoing stable cavitation and that cell lysis is produced by one or more transient events inside the cell.

Animals