Interdependence of Tissue Temperature, Cavitation, and Displacement Imaging During Focused Ultrasound Nerve Sonication

Focused ultrasound (FUS) peripheral neuromodulation has been linked to nerve displacement caused by the acoustic radiation force; however, the roles of cavitation and temperature accumulation on nerve modulation are less clear, as are the relationships between these three mechanisms of action. Temperature directly changes tissue stiffness and viscosity. Viscoelastic properties have been shown to affect cavitation thresholds in both theoretical and ex vivo models, but the direct effect of temperature on cavitation has not been investigated in vivo. Here, cavitation and tissue displacement were simultaneously mapped in response to baseline tissue temperatures of either 30 °C or 38 °C during sciatic nerve sonication in mice. In each mouse, the sciatic nerve was repeatedly sonicated at 1.1-MHz, 4-MPa peak-negative pressure, 5-ms pulse duration, and either 15- or 30-Hz pulse repetition frequency (PRF) for 10 s at each tissue temperature. Cavitation increased by 1.8–4.5 dB at a tissue temperature of 38 °C compared to 30 °C, as measured both by passive cavitation images and cavitation doses. Tissue displacement also increased by 1.3–
$1.8 \mu \text{m}$
at baseline temperatures of 38 °C compared to 30 °C. Histological findings indicated small increases in red blood cell extravasation in the 38 °C baseline temperature condition compared to 30 °C at both PRFs. A strong positive correlation was found between the inertial cavitation dose and displacement imaging noise, indicating the potential ability of displacement imaging to simultaneously detect inertial cavitation in vivo. Overall, tissue temperature was found to modulate both in vivo cavitation and tissue displacement, and thus, both tissue temperature and cavitation can be monitored during FUS to ensure both safety and efficiency.