Direct evidence of cavitation in vivo from diagnostic ultrasound

IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 2000

Experiments were performed in vitro to investigate the possibility of transient cavitation from short-pulse, diagnostic ultrasound under conditions comparable to clinical ultrasound examinations. An acoustic backscattering technique that utilizes 30-MHz pulsed ultrasound was employed to probe the potential of cavitation production by a clinical ultrasound scanner, specifically a Hewlett-Packard 77020A. Two calibrated, phasedarray HP imaging transducers with 2.5-and 5.0-MHz operating frequencies were driven in M-mode (single cycle) and Doppler mode (4 cycles) by the HP imaging system. Hydrophobic polystyrene spheres with an average diameter of 0.245 vm and Albunex, an echo contrast agent consisting of 1-to 10-pm bubbles with a human serum albumen coating, served as potential cavitation nuclei. Cavitation was detected in the water with polystyrene spheres at 2.5 MHz in both M-mode and Doppler mode at a peak negative acoustic pressure of 1.1 MPa or greater. Insonification at 5.0 MHz in either mode did not produce a detectable amount of cavitation, even with peak negative pressures as high as 1.2 MPa. Also, cavitation was not detected in water with the Albunex spheres at either frequency.

Ultrasonics Sonochemistry, 2007

In order to quantify the effects of exposure parameters under therapeutic conditions such as sonodynamic therapy, it is necessary initially to evaluate the inertial cavitation activity in vitro. In this study, the dependence of cavitation activity induced by the low-level dual-frequency ultrasound irradiation on exposure parameters has been studied. Experiments were performed in the near 150 kHz and 1 MHz fields in the progressive wave mode. It has been shown that at constant ultrasound energy the fluorescence intensity for continuous sonication is higher than for pulsed mode. With increasing the duty cycle of pulsed field, the inertial cavitation activity is increased. The activity of cavitation produced by simultaneous combined sonication by two ultrasound fields is remarkably higher than the algebraic sum of effects produced by fields separately (p-value < 0.05). This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is more effective in producing inertial cavitation activity at low-level intensity. Therefore, it is concluded that investigations in this combined ultrasound sonication can be useful in sonodynamic therapy for superficial tumors.

Journal of The Acoustical Society of America, 1998

Until the mid 1970s, it was generally assumed that, with the short pulses of ultrasound (US) used in medical diagnosis, there was little need for concern about the possibility of inertial cavitation in vivo. This assumption came into question when experimental evidence indicated that killing of fruit fly larvae by diagnostically relevant US was associated with the presence of gas in the respiratory apparatus of the organisms. Independent theoretical contributions by Flynn and Apfel in the early 1980s made it clear that complacency in regard to cavitation was not warranted. Later, the mammalian lung, as with larva, was shown to be particularly vulnerable when it contained air. Yet, overall evidence suggests that lung hemorrhage is not consistent with the classical picture of inertial cavitation. Most recently, however, hemolysis and hemorrhage associated with the use of contrast agents have provided nearly incontrovertible evidence of the occurrence of cavitation in vivo.

The Journal of the Acoustical Society of America, 1992

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. PACS numbers: 43.80.Gx, 43.25.Yw 1113 d. Acoust. Soc. Am. 91 (2),

Proceedings of The National Academy of Sciences, 2011

The purpose of this study was to develop a unified model capable of explaining the mechanisms of interaction of ultrasound and biological tissue at both the diagnostic nonthermal, noncavitational (<100 mW·cm −2 ) and therapeutic, potentially cavitational (>100 mW·cm −2 ) spatial peak temporal average intensity levels.

The Journal of the Acoustical Society of America, 2012

The mechanical index (MI) was formulated to gauge the likelihood of adverse bioeffects from inertial cavitation. However, the MI formulation did not consider bubble activity from stable cavitation. This type of bubble activity can be readily nucleated from ultrasound contrast agents (UCAs) and has the potential to promote beneficial bioeffects. Here, the presence of stable cavitation is determined numerically by tracking the onset of subharmonic oscillations within a population of bubbles for frequencies up to 7 MHz and peak rarefactional pressures up to 3 MPa. In addition, the acoustic pressure rupture threshold of an UCA population was determined using the Marmottant model. The threshold for subharmonic emissions of optimally sized bubbles was found to be lower than the inertial cavitation threshold for all frequencies studied. The rupture thresholds of optimally sized UCAs were found to be lower than the threshold for subharmonic emissions for either single cycle or steady state acoustic excitations. Because the thresholds of both subharmonic emissions and UCA rupture are linearly dependent on frequency, an index of the form I CAV = P r /f (where P r is the peak rarefactional pressure in MPa and f is the frequency in MHz) was derived to gauge the likelihood of subharmonic emissions due to stable cavitation activity nucleated from UCAs.

Ultrasound in Medicine &amp; Biology, 1997

A 20-MHz passive acoustic detector was used to quantify the amount of transient acoustic catitation occurring in a sample exposed to intense pulsed uttrasound. A dilute suspe&m of humau erythrocytes with and without a microbubble echo-contrast agent was exposed in vine to 500 W/cm' (SPPA) ultrasound of center frequency 1 MHz and tone burst duration 20,100,204 500 aud 1000 w at a puke repetition frequency of 20 Hz. Inertial cavitation occurring wit& the sample, as measured by the temporal average of the detector output, correlated well with hemolysis, suggesting that violent bubble is responsible for cell damage. The result also raises the prospect of cavitation mozdtoring as a possible predictor of adverse bioelkts when echo-contrast agents are used clinically.

Ultrasound in medicine …, 2010

Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells ...

Ultrasound in Medicine & Biology, 1991

Although no deleterious effects form diagnostic ultrasound have been reported in epidemiologic studies and surveys of widespread clinical usage (Ziskin and Petitti 1988), the conditions for the onset of transient cavitation must be investigated in the total evaluation of potential risks associated with diagnostic ultrasound applications. An extension of the results from the approximate theory developed by Holland and Apfel (1989) is applied in this paper to a population of nuclei to predict the onset of cavitation in host fluids with physical properties similar to those of biological fluids. From this analysis and from results of recent in vitro cavitation experiments, an index is developed which can gauge the likelihood of substantial microbubble growth in the presence of short-pulse, low-duty cycle diagnostic ultrasound.

rao.akin.ru

It is considered that with the use of high intensity ultrasound in medicine, it is necessary to avoid a cavitation regimen because of specific features of the physical nature of cavitation (e.g., random and stochastic character of its origination, weak reproducibility of localization and the shape of lesions in tissues, etc.). Nevertheless, the results of investigations carried out in different laboratories for the last years, demonstrate an opportunity of application in medicine of new, non-traditional methods based just on the use of ultrasound cavitation. For example, one of the methods of ultrasound surgery can be based on a preliminary creation in tissues gas bubbles decreasing cavitation thresholds and, therefore, a threshold of ablation of tissues. Thus, independently on the method of bubbles generation (e.g. with the use of ultrasound or, for example, by means of introduction of ultrasound contrast agents), localization of cavitation lesions and their shape become quite reproducible. The cavitation regimen can be used, for example, for ultrasonic ablation of deep-located brain structures through an intact skull to prevent excessive heating of skull bones. Cavitation can be used also as an effective mean of enhancement of the thermal effect of ultrasound due to creation gas bubbles in tissues, which increase significantly the sound attenuation. Cavitation is considered to be one of the basic mechanisms of the enhancement of the efficiency of the action of antitumoral chemicals on malignant tumors. One of the possible applications of cavitation in oncology can be based also on ablation of blood vessels surrounding a tumor, that will lead to blocking of blood supply and, therefore, to increasing of the destructive effect of ultrasound on the tumor. Prospects of the researches directed on the development of new acoustic methods for application in medicine based on the use of cavitation are discussed.