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Abstract

Many therapeutic applications of pulsed focused ultrasound are based on heating of detected lesions which may be localized in tissues at different depths under the skin. In order to concentrate the acoustic energy inside tissues at desired depths a new approach using a planar multi-element annular array transducer with an electronically adjusted time-delay of excitation of its elements, was proposed. The 7-elements annular array transducer with 2.4 MHz center operating frequency and 20 mm outer diameter was produced. All its elements (central disc and 6 rings) had the same radiating area. The main purpose of this study was to investigate thermal fields induced in bovine liver in vitro by pulsed focused ultrasonic beams with various acoustic properties and electronically steered focal plane generated from the annular array transducer used. The measurements were performed for the radiating beams with the 20 mm focal depth. In order to maximize nonlinear effects introducing the important local temperature rise, the measurements have been performed in two-layer media comprising of a water layer, whose thickness was specific for the transducer used and equal to 13 mm, and the second layer of a bovine liver with a thickness of 20 mm. The thickness of the water layer was determined numerically as the axial distance where the amplitude of the second harmonics started to increase rapidly. The measurements of the temperature rise versus time were performed using a thermocouple placed inside the liver at the focus of the beam. The temperature rise induced in the bovine liver in vitro by beams with the average acoustic power of 1W, 2 W and 3 W and duty cycle of 1/5, 1/15 and 1/30, respectively, have been measured. For each beam used the exposure time needed for the local tissue heating to the temperature of 43°C (used in therapies based on ultrasonic enhancement of drug delivery or in therapies involving stimulation of immune system by enhancement of the heat shock proteins expression) and to the temperature of 56°C (used in HIFU therapies) was determined. Two sets of measurements were done for each beam considered. First, the thermocouple measurement of the temperature rise was done and next, the real-time monitoring of dynamics of growth of the necrosis area by using ultrasonic imaging technique, while the sample was exposed to the same acoustic beam. It was found that the necrosis area becomes visible in the ultrasonic image only for beams with the average acoustic power of 3 W, although after cutting the sample the thermo ablated area was visible with the naked eye even for the beams with lower acoustic power. The quantitative analysis of the obtained results allowed to determine the exposure time needed to get the necrosis area visible in the ultrasonic image.
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Abstract

In many therapeutic applications of a pulsed focused ultrasound with various intensities the finite- amplitude acoustic waves propagate in water before penetrating into tissues and their local heating. Water is used as the matching, cooling and harmonics generating medium. In order to design ultrasonic probes for various therapeutic applications based on the local tissue heating induced in selected organs as well as to plan ultrasonic regimes of treatment a knowledge of pressure variations in pulsed focused nonlinear acoustic beams produced in layered media is necessary. The main objective of this work was to verify experimentally the applicability of the recently developed numerical model based on the Time- Averaged Wave Envelope (TAWE) approach (Wójcik et al., 2006) as an effective research tool for predicting the pulsed focused nonlinear fields produced in two-layer media comprising of water and tested materials (with attenuation arbitrarily dependent on frequency) by clinically relevant axially-symmetric therapeutic sources. First, the model was verified in water as a reference medium with known linear and nonlinear acoustic properties. The measurements in water were carried out at a 25◦C temperature using a 2.25 MHz circular focused (f/3.0) transducer with an effective diameter of 29 mm. The measurement results obtained for 8-cycle tone bursts with three different initial pressure amplitudes varied between 37 kPa and 113 kPa were compared with the numerical predictions obtained for the source boundary condition parameters determined experimentally. The comparison of the experimental results with those simulated numerically has shown that the model based on the TAWE approach predicts well both the spatial-peak and spatial-spectral pressure variations in the pulsed focused nonlinear beams produced by the transducer used in water for all excitation levels complying with the condition corresponding to weak or moderate source-pressure levels. Quantitative analysis of the simulated nonlinear beams from circular transducers with ka ≫ 1 allowed to show that the axial distance at which sudden accretion of the 2nd or higher harmonics amplitude appears is specific for this transducer regardless of the excitation level providing weak to moderate nonlinear fields. For the transducer used, the axial distance at which the 2nd harmonics amplitude suddenly begins to grow was found to be equal to 60 mm. Then, the model was verified experimentally for two-layer parallel media comprising of a 60-mm water layer and a 60-mm layer of 1.3-butanediol (99%, Sigma-Aldrich Chemie GmbH, Steinheim, Germany). This medium was selected because of its tissue-mimicking acoustic properties and known nonlinearity parameter B/A. The measurements of both, the peak- and harmonic-pressure variations in the pulsed nonlinear acoustic beams produced in two-layer media (water/1.3-butanediol) were performed for the same source boundary conditions as in water. The measurement results were compared with those simulated numerically. The good agreement between the measured data and numerical calculations has shown that the model based on the TAWE approach is well suited to predict both the peak and harmonic pressure variations in the pulsed focused nonlinear sound beams produced in layered media by clinically relevant therapeutic sources. Finally, the pulsed focused nonlinear fields from the transducer used in two-layer media: water/castor oil, water/silicone oil (Dow Corning Ltd., Coventry, UK), water/human brain and water/pig liver were predicted for various values of the nonlinearity parameter of tested media.
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