Imaging of tissue displacement induced during focused ultrasound neuromodulation in vivo

Our group has recently shown feasibility of FUS modulation of the peripheral nervous system (PNS) in vivo. However, the interplay between FUS and the PNS is not completely understood and has never been imaged. To unveil both the mechanism as well as provide an image-guided approach to modulation monitoring, a new modulation system was designed to simultaneously image the mechanical perturbation of the tissue during modulation in vivo. The system consisted of a 4.5 MHz HIFU confocally aligned with a 7.8 MHz imaging transducer. Activation of the sciatic nerve of the mouse was induced with parameters previously reported for successful modulation. 200 RF frames at a 10 kHz pulse repetition frequency were used for 1D cross-correlation (20 lambda window, 90% overlap) to calculate the inter-frame axial displacement before, during, and after modulation. Displacement maps overlaid on the B-mode images illustrate that once FUS is applied, downward displacement was detected where the highest displacement is located at the focus (9.8 micron average peak displacement). After FUS modulation, displacement steadily reduced to baseline (0.5–0.8 ms). Our findings indicate that FUS neuromodulation is associated with the radiation force effect and therefore successful application is dependent upon sufficient displacements induced.