Michael Zomack

Response of bubbles to diagnostic ultrasound: a unifying theoretical approach

Abstract:The scattering of ultrasound from bubbles of

Sound radiation of 3-MHz driven gas bubbles

\sim 1\mu

AN INVESTIGATION OF THE RELATIONSHIP BETWEEN ULTRASOUND ECHO ENHANCEMENT AND DOPPLER FREQUENCY SHIFT USING A PULSATILE ARTERIAL FLOW PHANTOM

m radius, such as used in contrast enhancers for ultrasound diagnostics, is studied. We show that sound scattering and “active” emission of sound from oscillating bubbles are not contradictory, but are just two different aspects derived from the same physics. Treating the bubble as a nonlinear oscillator, we arrive at general formulas for scattering and absorption cross-sections. We show that several well-known formulas are recovered in the linear limit of this ansatz. In the case of strongly nonlinear oscillations, however, the cross-sections can be larger than those for linear response by several orders of magnitude. The major part of the incident sound energy is then converted into emitted sound, unlike what happens in the linear case, where the absorption cross-sections exceed the scattering cross-sections.

Acoustically stimulated microbubbles in diagnostic ultrasound: properties and implications for diagnostic use

The sound scattering of free microbubbles released from strongly driven ultrasound contrast agents with brittle shell (e.g., Sonovist) is studied numerically. At high peak pressure of the driving pulses, the bubbles respond nonlinearly with cross sections pronouncedly larger than in the linear case; a large portion of the energy is radiated into high frequency ultrasound. Subsequent absorption of these high frequencies in the surrounding liquid (blood) diminishes the effective scattering cross section drastically. The absorption results in highly localized heating, with a substantial temperature rise within the first few microm from the bubble surface. The maximum heating in 1 microm distance is strongly dependent on driving pressure. Temperature elevations of more than 100 K can be achieved for amplitudes of Pa approximately 30 atm, which coincides with the highest pressures used in ultrasound diagnostics. The perfectly spherical collapses assumed here occur rarely, and the heating is highly localized and transient (approximately 10 micros). Therefore, a thermal hazard would only be expected at driving pressures beyond the diagnostic range.

Diagnostic value of contrast enhancement in vascular Doppler ultrasound

The sound radiation of 3-MHz acoustically driven air bubbles in liquid is analyzed with respect to possible applications in second harmonic ultrasound diagnostics devices, which have recently come into clinical use. In the forcing pressure amplitude Pa = 1–10 atm and ambient radius R0 = 0.5–5 µm parameter domain, a narrow regime around the resonance radius R0 ~ 1–1.5 µm and relatively modest Pa ~ 2–2.5 atm is identified in which optimal sound yield in the second harmonic is achieved while maintaining spherical stability of the bubble. For smaller Pa and larger R0 hardly any sound is radiated; for larger Pa bubbles become unstable toward nonspherical shape oscillations of their surface. The computation of these instabilities is essential for the evaluation of the optimal parameter regime. A region of slightly smaller R0 and Pa ~ 1–3 atm is best suited to achieve large ratios of the second harmonic to the fundamental intensity. Spherical stability is guaranteed in the suggested regimes for liquids with an enhanced viscosity compared to water, such as blood.

Microvascular imaging — results from a phase I study of the novel polymeric ultrasound contrast agent SHU 563A

“Microbubbles”, gaseous bubbles with microscopic diameters, are extremely effective scatterers of ultrasound. Because of their unique acoustic properties, microbubbles play a key role in the basic mode of action of ultrasound contrast media. This role is comparable to that of iodine in X-ray contrast media and of gadolinium in magnetic resonance contrast media [1, 2, 31]. However, single microbubbles, without any additional protection against gas diffusion (between gas bubble and carrier fluid, i.e. blood serum) have a very short lifetime of only a few seconds [4]. This is one of the reasons for the frequently described problems of reproducibility and efficacy with selfmade “contrast agents”. The underlying physico-chemical interactions of in vivo bubble stabilization are difficult and complex.

Sound scattering and local heating from pulse‐driven microbubbles

RATIONALE AND OBJECTIVES Based on the echo-enhancing effect of microbubbles, various agents have been developed to improve the diagnostic confidence in patients with inadequate Doppler signals. In the clinical trials of the echo enhancer Levovist, there were a few isolated cases in which the maximum flow velocities of the enhanced Doppler spectra appeared to higher than the velocities in the nonenhanced baseline spectra. This raised the concern that echo enhancement could give a false indication of maximum flow velocity. This study investigated whether a systematic association between echo enhancement and velocity shift exists. METHODS A pulsatile flow phantom that simulated the elasticity of blood vessels and the acoustic attenuation of extravascular tissue was used to compare enhanced with unenhanced Doppler spectra under accurately reproducible flow conditions. The experiments were carried out with varied sound attenuation and evaluated with dedicated spectral analysis software that included a special averaging tool. RESULTS Levovist enhanced the Doppler signal by 16 to 31 dB, and the enhanced and unenhanced power spectra presented identical distribution of spectral power density under all flow conditions. CONCLUSIONS The measurements gave no evidence that echo enhancement with Levovist falsifies the Doppler measurement of flow velocity.

Nonlinear response of microbubbles to pulsed diagnostic ultrasound

Ultrasound echo enhancement depends upon the enhancement of backscatter so that the intensity of the signal reflected back to the transducer is increased. However, the interaction between the incident ultrasound wave and the reflecting microbubbles is complex and dynamic. The incident ultrasound can drive the microbubbles into oscillation and, depending on the size of the microbubbles and the properties of their shells, that oscillation can become resonant. When some microbubble echo enhancers such as SHU 563A are exposed to high amplitude ultrasound this non-linear oscillation gives rise to a phenomenon called stimulated acoustic emission [1]. As the microbubbles oscillate they emit signals containing the second harmonic of the fundamental frequency to which they were exposed. With further increased transmit amplitude the microbubbles respond with high intensity broad-band signals and subsequent collapse. The signals originating from microbubbles due to stimulated acoustic emission can be used for specific detection of the ultrasound contrast agent with different techniques. This review will cover some of the basic principles involved and outline the diagnostic potential of stimulated acoustic emission and its use for microvascular imaging.