Real-time non-invasive control of ultrasound hyperthermia using high-frequency ultrasonic backscattered energy in ex vivo tissue and in vivo animal studies

<i>Objective.</i>A reliable, calibrated, non-invasive thermometry method is essential for thermal therapies to monitor and control the treatment. Ultrasound (US) is an effective thermometry modality due to its relatively high sensitivity to temperature changes, and fast data acquisition and processing capabilities.<i>Approach.</i>In this work, the change in backscattered energy (CBE) was used to control the tissue temperature non-invasively using a real-time proportional-integral-derivative (PID) controller. A clinical high-frequency US scanner was used to acquire radio-frequency echo data from<i>ex vivo</i>porcine tissue samples and<i>in vivo</i>mice hind leg tissue while the tissue was treated with mild hyperthermia by a focused US applicator. The PID controller maintained the focal temperature at approximately 40 °C for about 4 min.<i>Main results.</i>The results show that the US thermometry based on CBE estimated by a high-frequency US scanner can produce 2D temperature maps of a localized heating region and to estimate the focal temperature during mild hyperthermia treatments. The CBE estimated temperature varied by an average of ±0.85 °C and ±0.97 °C, compared to a calibrated thermocouple, in<i>ex vivo</i>and<i>in vivo</i>studies, respectively. The mean absolute deviations of CBE thermometry during the controlled hyperthermia treatment were ±0.45 °C and ±0.54 °C in<i>ex vivo</i>and<i>in vivo,</i>respectively.<i>Significance.</i>It is concluded that non-invasive US thermometry via backscattered energies at high frequencies can be used for real-time monitoring and control of hyperthermia treatments with acceptable accuracy. This provides a foundation for an US mediated drug delivery system.