The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has recently gained momentum. Guidance is provided by either magnetic resonance imaging (MRI) or conventional B-mode ultrasound imaging, each with its own advantages and disadvantages. The main limitation of ultrasound imaging is its inability to provide temperature measurements over the ranges corresponding to the target temperatures during ablative thermal therapies (between 55 °C and 70 °C). Here, variations in ultrasound backscattered energy (ΔBSE) were used to monitor temperature increases in liver tissue up to an absolute value of 90 °C during and after HIFU treatment. In vitro experimental measurements were performed in 47 bovine liver samples using a toroidal HIFU transducer operating at 2.5 MHz to increase the temperature of tissues. An ultrasound imaging probe working at 7.5 MHz was placed in the center of the HIFU transducer to monitor the backscattered signals. The free-field acoustic power was set to 9 W, 12 W or 16 W in the different experiments. HIFU sonications were performed for 240 s using a duty cycle of 83 % to allow ultrasound imaging and raw radiofrequency data acquisition during exposures. Measurements showed a linear relationship between ΔBSE (in dB) and temperature (r = 0.94, p < 0.001) over a temperature range from 37 °C to 90 °C, with a high reliability of temperature measurements below 75 °C. Monitoring can be performed at the frame rate of ultrasound imaging scanners with an accuracy within an acceptable threshold of 5 °C, given the temperatures targeted during thermal ablations. If the maximum temperature reached is below 70 °C, ΔBSE is also a reliable approach for estimating the temperature during cooling. Histological analysis shown the impact of the treatment on the spatial arrangement of cells that can explain the observed variation of ΔBSE. These results demonstrate the ability of ΔBSE measurements to estimate temperature in ultrasound images within an effective therapeutic range. This method can be implemented clinically and potentially applied to other thermal-based therapies.

OBJECTIVE: A real-time and non-invasive thermometry technique is essential in thermal therapies to monitor and control the treatment. Ultrasound is an attractive thermometry modality due to its relatively high sensitivity to change in temperature and fast data acquisition and processing capabilities. A temperature-sensitive acoustic parameter is required for ultrasound thermometry in order to track the changes in that parameter during the treatment. Currently, the main ultrasound thermometry methods are based on variation in the attenuation coefficient, the change in backscattered energy of the signal (CBE), the backscattered radio-frequency (RF) echo-shift due to change in the speed of sound and thermal expansion of the medium, and change in the amplitudes of the acoustic harmonics. In this work, an ultrasound thermometry method based on second harmonic CBE (CBEh2) and combined fundamental and second harmonic CBE (CBEcomb) is used to produce 2D temperature maps, detect localized heated region generated by low intensity focused ultrasound (LIFU), and control temperature in the heated region.
METHODS: Ex vivo pork muscle tissue samples were exposed to localized LIFU heating source and 2D temperature maps were produced from the RF data acquired by a 4.2 MHz linear array probe using a Verasonics Vantage™ ultrasound scanner (Verasonics Inc., Redmond, WA) after the exposure. Calibrated needle thermocouples were also placed in the ex vivo tissue sample close to the LIFU focal zone for temperature calibration purposes. The estimated temperature maps were the established echo-shift technique. A tissue motion compensation algorithm was also used to reduce the susceptibility to motion artifacts.
RESULTS: 2D temperature maps were generated using CBE of acoustic harmonic and echo-shift techniques. The results show a direct correlation between the CBE of acoustic harmonics and focal tissue temperature for a range of temperatures from 37 °C (baseline) to 47 °C.
CONCLUSIONS: The findings of this study show that the CBE of acoustic harmonics technique can be used to noninvasively estimate temperature change in tissue in the hyperthermia temperature range.

Purpose: A real-time noninvasive thermometry technique is required to estimate the temperature distribution during hyperthermia to monitor and control the treatment. The main objective of this study is to demonstrate the possibility of detecting change in backscatter energy (CBE) of acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues in which the temperature was locally increased within the hyperthermia regime. Materials and Methods: A peristaltic pump was used to circulate hot water through a needle inserted inside the samples to locally increase the temperature from 26 °C to 46 °C. The CBE of acoustic harmonics were used to identify the location of temperature changes in the samples. A conventional echo-shift technique was also implemented for comparison. Data collection was performed for two conditions to investigate the effect of motion on both techniques by: (1) inducing vibration in the sample through the peristatic pump and, (2) subsequently with no sample vibration while the pump was off. Results: Harmonics were able to determine the location of temperature rise in the presence and absence of vibration. In gel phantom, the mean contrast to noise ratio (CNR) in CBE maps reduced by a factor of 0.86 due to vibration whereas in gradient maps the CNR reduced by a factor of 8.3. Conclusions: The findings of this study suggest that the change in backscatter energy of acoustic harmonics can potentially be used to develop a noninvasive ultrasound-based thermometry technique with lower susceptibility to motion artifacts compared to the echo-shift method.