Focused ultrasound (FUS) is an emerging technique for neuromodulation due to its noninvasive application and high depth penetration. Recent studies have reported success in modulation of brain circuits, peripheral nerves, ion channels, and organ structures. In particular, neuromodulation of peripheral nerves and the underlying mechanisms remain comparatively unexplored in vivo. Lack of methodologies for FUS targeting and monitoring impede further research in in vivo studies. Thus, we developed a method that non-invasively measures nerve engagement, via tissue displacement, during FUS neuromodulation of in vivo nerves using simultaneous high frame-rate ultrasound imaging. Using this system, we can validate, in real-time, FUS targeting of the nerve and characterize subsequent compound muscle action potentials (CMAPs) elicited from sciatic nerve activation in mice using 0.5 to 5 ms pulse durations and 22 - 28 MPa peak positive stimulus pressures at 4 MHz. Interestingly, successful motor excitation from FUS neuromodulation required a minimum interframe nerve displacement of 18 μm18~\mu m without any displacement incurred at the skin or muscle levels. Moreover, CMAPs detected in mice monotonically increased with interframe nerve displacements within the range of 18 to 300 μm300~\mu m . Thus, correlation between nerve displacement and motor activation constitutes strong evidence FUS neuromodulation is driven by a mechanical effect given that tissue deflection is a result of highly focused acoustic radiation force.

中文翻译：

---

聚焦超声周围神经神经调节的位移成像


聚焦超声（FUS）因其无创应用和高深度穿透而成为一种新兴的神经调节技术。最近的研究报告在调节脑回路、周围神经、离子通道和器官结构方面取得了成功。特别是，周围神经的神经调节及其潜在机制在体内仍然相对未经探索。缺乏 FUS 靶向和监测方法阻碍了体内研究的进一步研究。因此，我们开发了一种方法，在使用同步高帧率超声成像对体内神经进行 FUS 神经调节期间，通过组织位移非侵入性地测量神经参与情况。使用该系统，我们可以实时验证 FUS 神经靶向，并表征使用 0.5 至 5 ms 脉冲持续时间和 22 - 28 MPa 峰值正刺激，小鼠坐骨神经激活引起的后续复合肌肉动作电位 (CMAP) 4 MHz 的压力。有趣的是，FUS 神经调节成功的运动激发需要 18 μm18~μ m 的最小帧间神经位移，而不会在皮肤或肌肉水平产生任何位移。此外，在小鼠中检测到的CMAP在18至300μm300~μm范围内随着帧间神经位移单调增加。因此，神经位移和运动激活之间的相关性构成了 FUS 神经调节是由机械效应驱动的强有力的证据，因为组织偏转是高度聚焦的声辐射力的结果。