Harmonic Motion Imaging for Focused Ultrasound (HMIFU): Initial in vivo results

Abstract

The capability of Harmonic Motion Imaging for Focused Ultrasound (HMIFU) for real-time monitoring of tissue stiffness changes during thermal therapy was previously demonstrated ex vivo. In this paper, initial feasibility of the HMIFU for thermal ablation generation and monitoring is shown in a transgenic mouse model of breast cancer in vivo. The HMIFU system consists of a 4.5-MHz focused ultrasound (FU) transducer and an ultrasound imaging transducer. The ultrasound imaging transducer can be a 3.3-MHz phased-array transducer for monitoring relative tissue stiffness changes during thermal treatment, or a 7.5-MHz single-element pulse echo transducer for tumor detection and post-treatment assessment. An Amplitude-modulated FUS beam was used to generate an oscillatory radiation force at the tumor region. The optimal AM frequency was determined using a linear chirp test frequency range of 10 to 30 Hz. The acoustic intensity (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">spta</sub> ) for ablation and probing were equal to 1050 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 236 W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , respectively. The spectrum of the FUS beam and its harmonics from the acquired RF signals were filtered out prior to displacement estimation. 1D cross-correlation (window size = 1 mm and 85% overlap) was performed to estimate the resulting tissue axial displacement. The average peak-to-peak displacement amplitude before and after lesion formation were found to be equal to 27.34?1.34 ?m and 20.98?1.82 ?m, respectively. The result show statistically-significant difference (p-value < 0.001). Cell death in the tumor area was confirmed by gross histopathology. The HMIFU was shown capable of monitoring and localizing thermal ablation of tumors in vivo. In conclusion, The HMIFU can be used as a guidance tool for visualization of the targeted region and monitoring of the relative tissue stiffness changes during thermal treatment so that the treatment procedure can be performed in both a cost- and time-efficient manner.