Simultaneous Evaluation of Thermal and Non-Thermal Effects of High-Intensity Focused Ultrasound on a Tissue-Mimicking Phantom

Physiologically relevant phantoms with high reliability are essential for extending the therapeutic applications of high-intensity therapeutic ultrasound. Here we describe a tissue-mimicking phantom capable of quantifying temperature changes and observing non-thermal phenomena by high-intensity therapeutic ultrasound. Using polydiacetylene liposomes, we fabricated agar-based polydiacetylene hydrogel phantoms (PHPs) that not only respond to temperature, but also have acoustic properties similar to those of human liver tissue. The color of PHPs changed from blue to red depending on the temperature in the range 40°C-70°C, where the red/blue ratio of PHP had a good linearity of 99.06% for the temperature changes. Furthermore, repeated high-intensity focused ultrasound led to histotripsy on the PHP with liquefied and damaged areas measuring 0.7 and 4.0 cm2, respectively, at the signal generator amplitude setting voltage of 80 mV. Our results indicate not only the usability of the thermochromic phantom, but also its potential for evaluating non-thermal phenomena in various high-intensity focused ultrasound therapies.