Ultrasound assessment of the conversion of sound energy into heat in tissue phantoms enriched with magnetic micro‐ and nanoparticles

PURPOSE: Nowadays, the improvement of ultrasonic hyperthermia therapy is often achieved by adding hard particles to the sonicated medium in order to increase the heating efficiency. The explanation of the phenomenon of ultrasonic heating still requires testing on tissue mimicking materials (TMMs), enriched with particles of different sizes and physical properties. Our goal was to determine, by comparing their quantitative acoustic properties, which TMMs, with magnetic micro- or nanoparticles, convert more ultrasonic energy into heat or which of the particles embedded in the agar gel act as more effective thermal sonosensitizers. METHODS: We manufactured a pure agar gel and an agar gel with the addition of magnetic micro- or nanoparticles in two proportions of 8 and 16 mg/ml. Ultrasound quantitative techniques, the broadband reflection substitution technique and backscattered spectrum analysis were used to characterize the samples by speed of sound (SOS), frequency-dependent attenuation, and backscattering coefficients. The integrated backscattering coefficients were also calculated. The quantitative parameters, scattering, and attenuation coefficients of ultrasound in phantoms with micro- and nanoparticles were estimated. Based on the attenuation and scattering of ultrasound in the samples, the ultrasonic energy absorption, which determines the heating efficiency, was evaluated. Additionally, the temperature increase during sonication of the phantoms by an ultrasonic beam was directly measured using thermocouples. RESULTS: The density of the materials with nanoparticles was higher than for the materials with microparticles with the same fractions of particles. The SOS for all materials ranged from 1489 to 1499 m/s. The attenuation in the whole frequency range (3-8 MHz) was higher for the materials with nanoparticles than for the materials with microparticles. For the materials with the lower content (8 mg/ml) of particles, the attenuation coefficient was 0.2 dB/(MHz cm). For the 16 mg/ml concentration of nanoparticles and microparticles, the attenuation coefficients were 0.66 and 0.45 dB/(MHz cm), respectively. The value of backscattering coefficient in the whole frequency range was greater for the materials with microparticles than for the materials with nanoparticles. The values of the integrated backscattering coefficient were 0.05 and 0.08 1/m for the materials with nanoparticles and 0.46 and 0.82 1/m for the materials with microparticles and concentrations of 8 and 16 mg/ml, respectively. The rates of temperature increase in the first 3 s due to ultrasonic heating were higher for the materials with nanoparticles than for the materials with microparticles. CONCLUSIONS: Based on acoustical measurements, we confirmed that all materials can be used as tissue phantoms in the study of ultrasonic hyperthermia, as their properties were in the range of soft tissue properties. We found that the nanoparticle-doped materials had greater attenuation and smaller scattering of ultrasound than the materials with microparticles, so absorption in these materials is greater. Thus, the TMMs with nanoparticles convert more acoustic energy into heat and we conclude that magnetic nanoparticles are more effective thermal sonosensitizers than microparticles. This conclusion is confirmed by direct measurement of the temperature increase in the samples subjected to sonification.