Biological Effects of Low-Frequency Shear Strain: Physical Descriptors.

Biological effects of megahertz-frequency diagnostic ultrasound are thoroughly monitored by professional societies throughout the world. A corresponding, thorough, quantitative evaluation of the archival literature on the biological effects of low-frequency vibration is needed. Biological effects, of course, are related directly to what those exposures do physically to the tissue-specifically, to the shear strains that those sources produce in the tissues. Instead of the simple compressional strains produced by diagnostic ultrasound, realistic sources of low-frequency vibration produce both fast (∼1,500 m/s) and slow (1-10 m/s) waves, each of which may have longitudinal and transverse shear components. Part 1 of this series illustrates the resulting strains, starting with those produced by longitudinally and transversely oscillating planes, through monopole and dipole sources of fast waves and, finally, to the case of a sphere moving in translation-the simplest model of the fields produced by realistic sources.

Oestreicher and elastography.

A sphere moving back and forth in tissue generates the kinds of complex displacement fields that are used in elastography. The analytical solution of Hans Oestreicher for this phenomenon [(1951). J. Acoust. Soc. Am. 23, 704-714] gives an understanding of the transverse and longitudinal, fast and slow waves that are generated. The results suggest several ways to determine the absorption coefficients of tissues, which together with phase velocity permit the computation of both the real shear modulus and the shear viscosity as functions of frequency.

Physical models of tissue in shear fields.

This review considers three general classes of physical as opposed to phenomenological models of the shear elasticity of tissues. The first is simple viscoelasticity. This model has a special role in elastography because it is the language in which experimental and clinical data are communicated. The second class of models involves acoustic relaxation, in which the medium contains inner time-dependent systems that are driven through the external bulk medium. Hysteresis, the phenomenon characterizing the third class of models, involves losses that are related to strain rather than time rate of change of strain. In contrast to the vast efforts given to tissue characterization through their bulk moduli over the last half-century, similar research using low-frequency shear data is in its infancy. Rather than a neat summary of existing facts, this essay is a framework for hypothesis generation-guessing what physical mechanisms give tissues their shear properties.

Shear strain from irrotational tissue displacements near bubbles.

Particle displacements can be much greater near bubbles than they would be in a homogeneous liquid or tissue when exposed to an acoustic wave. In a plane wave, shear and bulk strains are of the same order of magnitude. In contrast, for a bubble oscillating close to its resonance frequency, the shear strain in the medium near the bubble is roughly four orders of magnitude greater than the bulk strain. This can lead to shear strains of a few percent even with acoustic excitation pressures far below the pressure thresholds required to cause inertial cavitation. High shear strains near oscillating bubbles could potentially be the cause of bioeffects. After acoustic exposures at audio frequencies, hemorrhages in tissues as diverse as lung, liver, and kidney have been observed at shear strains on the order of 1%.

Elastography in the management of liver disease.

Normal liver tissue is soft and pliable. With inflammation, however, many of the cells die and are replaced by collagenous fibrils and the tissue gets stiffer. The progress is often slow-extending over decades in many cases. When liver stiffness increases by a factor of about five, the condition is called cirrhosis, a disease with serious medical implications. After the onset of cirrhosis, the probability of developing hepatic cancer increases at the rate of about 5% per year. Precise, noninvasive measurement of liver stiffness, a simple application of elastography, promises to be a safe, inexpensive method to monitor the progress of liver patients, improve outcome, save many lives and much suffering and reduce the cost of medical care.

The risk of exposure to diagnostic ultrasound in postnatal subjects: nonthermal mechanisms.

This review examines the nonthermal physical mechanisms by which ultrasound can harm tissue in postnatal patients. First the physical nature of the more significant interactions between ultrasound and tissue is described, followed by an examination of the existing literature with particular emphasis on the pressure thresholds for potential adverse effects. The interaction of ultrasonic fields with tissue depends in a fundamental way on whether the tissue naturally contains undissolved gas under normal physiologic conditions. Examples of gas-containing tissues are lung and intestine. Considerable effort has been devoted to investigating the acoustic parameters relevant to the threshold and extent of lung hemorrhage. Thresholds as low as 0.4 MPa at 1 MHz have been reported. The situation for intestinal damage is similar, although the threshold appears to be somewhat higher. For other tissues, auditory stimulation or tactile perception may occur, if rarely, during exposure to diagnostic ultrasound; ultrasound at similar or lower intensities is used therapeutically to accelerate the healing of bone fractures. At the exposure levels used in diagnostic ultrasound, there is no consistent evidence for adverse effects in tissues that are not known to contain stabilized gas bodies. Although modest tissue damage may occur in certain identifiable applications, the risk for induction of an adverse biological effect by a nonthermal mechanism due to exposure to diagnostic ultrasound is extremely small.

Ultrasound enhancement of fibrinolysis at frequencies of 27 to 100 kHz.

Ultrasound (US) accelerates enzymatic fibrinolysis in vitro and in animal models, and may be a useful adjunctive therapy for clinical thrombolysis. Successful clinical application will depend on the selection of appropriate US parameters to optimize fibrinolytic enhancement while limiting adverse effects, including heating. Most studies have been done at megahertz frequencies, but tissue penetration is better and heating less at lower frequencies. We have, therefore, now investigated the effects of continuous-wave and pulsed US on fibrinolysis at midkilohertz frequencies. Fibrinolysis with tissue plasminogen activator (t-PA) was measured by solubilization of radiolabeled fibrin exposed to a calibrated US field in a temperature-controlled water bath. There was significant enhancement of fibrinolysis at frequencies of 27, 40 and 100 kHz, with the greatest effect observed at 27 kHz. The largest effect was observed with continuous-wave US, but significant acceleration was also observed with peak intensities of 1 W/cm(2) duty cycles of 10% and 1%. At a 10% duty cycle, there was approximately 60% of the fibrinolytic enhancement observed with continuous-wave exposure, indicating a clear advantage of pulsing to optimize fibrinolytic effect and limit exposure. We conclude that US in the range of 27 to 100 kHz is effective in accelerating fibrinolysis at intensities and pulsing conditions that minimize the probability of heating and cavitation in clinical applications.