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102 D. Maulik<br />

liquid, the oscillatory motion generates a steady eddying<br />

flow, often of high velocity; this phenomenon<br />

is known as microstreaming. Intracellular microstreaming<br />

can also occur from a vibrating cell membrane<br />

close to an asymmetrically oscillating cavity.<br />

That stable cavitation can induce bioeffects under experimental<br />

conditions has been demonstrated by various<br />

investigators [39, 40]. However this type of cavitation<br />

has not been shown to be of any significance<br />

in bioeffects considerations.<br />

Cavitational phenomenon in a medium related to<br />

ultrasound exposure is controlled by many factors including<br />

acoustic characteristics of field, ambient factors,<br />

and cavitational potential of the medium. These<br />

are elaborated below.<br />

Acoustic Characteristics for Cavitation<br />

The critical acoustic factors responsible for producing<br />

inertial collapse of a resonating bubble are the maximum<br />

rarefaction and compressional pressures. The<br />

greater the rarefactional or negative pressure, the<br />

more the bubble expands preceding collapse. The<br />

greater the compressional or positive pressure, the<br />

more intense is the inertial pressure of the collapse.<br />

Both factors determine the intensity of the bubble<br />

collapse and the consequent severe local disruption.<br />

However, positive or negative pressure spikes of very<br />

short duration (< 0.01 ls) are not of significance.<br />

With pulsed ultrasound, the pulse length, duty cycle<br />

and frequency affect cavitation. Shorter pulses and<br />

lower pulse repetition frequency increase the cavitational<br />

intensity threshold. Indeed, it has been suggested<br />

that cavitation may probably be prevented if<br />

the pulse duration is sufficiently reduced [41], which<br />

has led to the general assumption that with medical<br />

diagnostic pulsed echo ultrasound, the pulse duration<br />

is too short to produce any cavitational activity. However,<br />

it has been demonstrated that microsecondlength<br />

pulses used in diagnostic pulsed-echo equipment<br />

may cause inertial cavitation if gas nuclei of<br />

suitable size are present in the medium and if the<br />

acoustic parameters of the ultrasound are appropriate.<br />

Moreover, the intensity threshold for producing<br />

inertial cavitation has been shown to be 1±10 W/cm 2<br />

for microsecond-length pulses [42]. Temporal maximum<br />

intensity far exceeding this level can occur in<br />

diagnostic ultrasound imaging. The risk is potentially<br />

greater with some pulsed Doppler systems because of<br />

the higher pulse repetition frequency and intensity.<br />

Ambient Pressure and Temperature<br />

Ambient pressure and cavitational activity are inversely<br />

related, so an increase in the former increases<br />

the threshold intensities for cavitation. Conversely,<br />

higher temperature facilitates cavitation by decreasing<br />

the solubility of gas in the medium which will lead to<br />

microbubbles that serve as nuclei for cavitation to occur.<br />

Tissue Characteristics for Cavitation<br />

Prerequisites for cavitational activity are the quantity<br />

and size of the gas nuclei present in the medium. As<br />

mentioned earlier, even microsecond-length pulses<br />

have the potential to induce inertial cavitation, depending<br />

on the presence of micronuclei of sufficient<br />

size. Unfortunately, gaseous micronuclei are not easily<br />

detected. Although it has been disputed in the past,<br />

there is ample evidence that strongly suggests the<br />

presence of such nuclei in mammalian tissues. Such<br />

evidence includes studies on decompression syndrome<br />

in humans, experiments with lithotripter in<br />

dogs [43], and the observation in mice that application<br />

of hydrostatic pressure increased the threshold<br />

for sonar-related tissue damage [44]. The presence of<br />

such nuclei and insonation-related cavitation has<br />

been demonstrated in mammals by Lee and Frizzell<br />

[45] who observed hydrostatic pressure and temperature-dependent<br />

neonatal mouse hind limbparalysis<br />

due to ultrasound exposure. Aerated lung tissue with<br />

its blood ± gas interface is particularly susceptible to<br />

the presence of gas nuclei. This is further discussed<br />

below.<br />

Biological Effects of Inertial Cavitation<br />

A collapsing cavity can result in cell lysis, dissociation<br />

of water vapor, and generation of free radicals.<br />

The mechanism by which inertial cavitation causes<br />

cell destruction involves generation of intense local<br />

heat and pressure and the generation of shear forces<br />

by the bubble implosion [14, 46]. Furthermore, it has<br />

recently been suggested that such implosions may occur<br />

within the cell; such an event may not lyse the<br />

cells but may give rise to free radicals. Continuouswave<br />

high-intensity ultrasound has been shown to<br />

produce free radicals in aqueous biological medium<br />

by inertial cavitation [47]. The free radicals may affect<br />

macromolecules. Thymine base alteration, chromosomal<br />

agglomeration, and mutation have been observed<br />

in insonated but intact cells. Irreversible deterioration<br />

of the enzyme A-chymotrypsin has been reported<br />

following production of radicals from insonation-induced<br />

cavitation [48]. Similarly, other toxic<br />

products such as hydrogen peroxide may induce adverse<br />

effects in a biological system. It should be emphasized<br />

that these phenomena have been noted<br />

mostly during in vitro experiments and never in relation<br />

to any human exposure.

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