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.
Image-guided High Intensity Focused Ultrasound (HIFU) technique is dynamically developing technology for treating solid tumors due to its non-invasive nature. Before a HIFU ablation system is ready for use, the exposure parameters of the HIFU beam capable of destroying the treated tissue without damaging the surrounding tissues should be selected to ensure the safety of therapy. The purpose of this work was to select the threshold acoustic power as well as the step and rate of movement of the HIFU beam, generated by a transducer intended to be used in the HIFU ablation system being developed, by using an array of thermocouples and numerical simulations. For experiments a bowl-shaped 64-mm, 1.05 MHz HIFU transducer with a 62.6 mm focal length (f-number 0.98) generated pulsed waves propagating in two-layer media: water/ex vivo pork loin tissue (50 mm/40 mm) was used. To determine a threshold power of the HIFU beam capable of creating the necrotic lesion in a small volume within the tested tissue during less than 3 s each tissue sample was sonicated by multiple parallel HIFU beams of different acoustic power focused at a depth of 12.6 mm below the tissue surface. Location of the maximum heating as well as the relaxation time of the tested tissue were determined from temperature variations recorded during and after sonication by five thermo-couples placed along the acoustic axis of each HIFU beam as well as from numerical simulations. The obtained results enabled to assess the location of each necrotic lesion as well as to determine the step and rate of the HIFU beam movement. The location and extent of the necrotic lesions created was verified using ultrasound images of tissue after sonication and visual inspection after cutting the samples. The threshold acoustic power of the HIFU beam capable of creating the local necrotic lesion in the tested tissue within 3 s without damaging of surrounding tissues was found to be 24 W, and the pause between sonications was found to be more than 40 s.
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.
Therapeutic and surgical applications of focused ultrasound require monitoring of local temperature rises induced inside tissues. From an economic and practical point of view ultrasonic imaging techniques seem to be the most suitable for the temperature control. This paper presents an implementation of the ultrasonic echoes displacement estimation technique for monitoring of local temperature rise in tissue during its heating by focused ultrasound The results of the estimation were compared to the temperature measured with thermocouple. The obtained results enable to evaluate the temperature fields induced in tissues by pulsed focused ultrasonic beams using non-invasive imaging ultrasound technique