Thomas J. Matula

Inertial cavitation dose and hemolysis produced in vitro with or without Optison

Gas-based contrast agents (CAs) increase ultrasound (US)-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC dose (ICD) (cumulated root mean squared [RMS] broadband noise amplitude; frequency domain) and 1.1-MHz US-induced hemolysis in whole human blood was explored with Optison; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: 1. peak negative acoustic pressure (P-), 2. Optison concentration, 3. pulse duration and 4. total exposure duration and Optison concentration. P- thresholds for hemolysis and ICD were approximately 0.5 MPa. ICD and hemolysis were detected at Optison concentrations >/= 0.01 V%, and with pulse durations as low as four or two cycles, respectively. Hemolysis and ICD evolved as functions of time and Optison concentration; final hemolysis and ICD values depended on initial Optison concentration, but initial rates of change did not. Within series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p < 0.001.

The disappearance of ultrasound contrast bubbles: Observations of bubble dissolution and cavitation nucleation

The destruction process of biSphere and Optison ultrasound (US) contrast microbubbles were studied at 1.1 MHz. High-amplitude tone bursts caused shell disruption and/or fragmentation of the microbubbles, leading to dissolution of the freed gas. The bubble destruction and subsequent dissolution process was imaged with a high pulse-repetition frequency (PRF) 10-cycle, 5-MHz bistatic transducer configuration. Three types of dissolution profiles were measured: In one case, biSphere microbubbles showed evidence of dissolution through resonance, during which a temporary increase in the scattering amplitude was observed. In another case, both biSphere and Optison microbubbles showed evidence of fragmentation, during which the scattering amplitude decreased rapidly. Finally, in some cases, we observed the impulsive growth and subsequent rapid decay of signals that appear to be due to cavitation nucleation. Simulations of bubble dissolution curves show good agreement with experiments.

Estimating the shell parameters of SonoVue ® microbubbles using light scattering

Experiments were performed to measure the dynamical response of individual SonoVue microbubbles subjected to pulsed ultrasound. Three commonly used bubble dynamic models (i.e., Hoffs, Sarkars, and linearized Marmottants models) were compared to determine the most appropriate model for fitting to the experimental data. The models were evaluated against published optical microscopy data. The comparison suggests that it is difficult to rank these models for lipid-shelled microbubbles undergoing small-amplitude oscillations, because under these conditions the shell parameters in these models are closely related. A linearized version of the Marmottant model was used to estimate the shell parameters (i.e., shear modulus and shear viscosity) of SonoVue microbubbles from the experimental light scattering data, as a function of ambient microbubble radius. The SonoVue microbubble shell elasticity and dilatational viscosity increase with ambient bubble radius, in agreement with previously published data. The results suggest that light scattering, used in conjunction with one of several popular bubble dynamics models, is effective at characterizing microbubble response and evaluating shell parameters.

Mechanisms of lesion formation in high intensity focused ultrasound therapy

The lesions generated by high intensity ultrasound were studied in transparent tissue phantoms premixed with and without ultrasound contrast agents (UCA) at 1.1- and 3.5-MHz acoustic waves. Generation of small bubbles was observed at the very beginning of exposure, whereas cigar-shaped thermal lesions began to form at the focus after a delay. After further heating, boiling occurred and changed the lesion to tadpole-shape, with advancement toward the transducer. Broadband noise was detected in phantoms with UCA initially. UCA also lowered the pressure threshold and enlarged the lesion. Although thermal and cavitation effects are believed to be both important in lesion formation, tadpole-shaped transformation results from boiling activity.

Bjerknes force and bubble levitation under single-bubble sonoluminescence conditions

Bubble levitation in an acoustic standing wave is re-examined here for the case of single-bubble sonoluminescence. The equilibrium position of the bubble is calculated by equating the average Bjerknes force with the average buoyancy force. The predicted values, as a function of pressure amplitude, are compared with experimental measurements. Our measurements indicate that the equilibrium position of the bubble shifts away from the pressure antinode as the drive pressure increases, in qualitative agreement with calculations, but unexpected when only linear theory is considered [A. Eller, J. Acoust. Soc. Am. 43, 170 (1968)]. The Bjerknes force also provides an upper limit to the drive pressure in which a bubble can be levitated near (and above) a pressure antinode, even in the absence of shape instabilities.

The acoustic emissions from single-bubble sonoluminescence

Detailed measurements of the acoustic emissions from single-bubble sonoluminescence have been made utilizing both a small 200-μm aperture PVDF needle hydrophone, and a focused 10-MHz transducer. Signals obtained with the needle hydrophone show a fast (5.2 ns), probably bandlimited rise time and relatively large pulse amplitude (≈1.7 bar). Below the sonoluminescence threshold, the emissions are observable, but considerably smaller in amplitude (≈0.4 bar). Several signals are observed with the 10-MHz transducer and correspond to acoustic emissions from the bubble during the main collapse, as well as from the rebounds. Experiments reveal that the acoustic emissions occur at or near the minimum bubble radius. Calculations of the peak pressures and pulse widths are compared with experimental data.

Blood vessel rupture by cavitation

Cavitation is thought to be one mechanism for vessel rupture during shock wave lithotripsy treatment. However, just how cavitation induces vessel rupture remains unknown. In this work, a high-speed photomicrography system was set up to directly observe the dynamics of bubbles inside blood vessels in ex vivo rat mesenteries. Vascular rupture correlating to observed bubble dynamics were examined by imaging bubble extravasation and dye leakage. The high-speed images show that bubble expansion can cause vessel distention, and bubble collapse can lead to vessel invagination. Liquid jets were also observed to form. Our results suggest that all three mechanisms, vessel distention, invagination and liquid jets, can contribute to vessel rupture.

Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro

Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison or Sonazoid microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters.

Radial Response of Individual Bubbles Subjected to Shock Wave Lithotripsy Pulses In Vitro

Direct measurements of individual bubble oscillations in lithotripsy fields have been performed using light-scattering techniques. Studies were performed with bubble clouds in gassy water as well as single levitated bubbles in degassed water. There is direct evidence that the bubble survives the inertial collapse, rebounding several times before breaking up. Bubble dynamics calculations agree well with the observations, provided that vapor trapping (a reduction in condensation during bubble collapse) is included. Furthermore, the afterbounces are dominated by vapor diffusion, not gas diffusion. Vapor trapping is important in limiting the collapse strength of bubbles, and in sonochemical activity.

Nonlinear contrast enhancement in photoacoustic molecular imaging with gold nanosphere encapsulated nanoemulsions

A composite contrast agent, a nanoemulsion bead with assembled gold nanospheres at the interface, is proposed to improve the specific contrast of photoacoustic molecular imaging. A phase transition in the beads core is induced by absorption of a nanosecond laser pulse with a fairly low laser fluence (∼3.5 mJ/cm2), creating a transient microbubble through dramatically enhanced thermal expansion. This generates nonlinear photoacoustic signals with more than 10 times larger amplitude compared to that of a linear agent with the same optical absorption. By applying a differential scheme similar to ultrasound pulse inversion, more than 40 dB contrast enhancement is demonstrated with suppression of background signals.