Displacement Imaging During Focused Ultrasound Median Nerve Modulation: A Preliminary Study in Human Pain Sensation Mitigation

Focused ultrasound (FUS)-based viscoelastic imaging techniques using high frame rate (HFR) ultrasound to track tissue displacement can be used for mechanistic monitoring of FUS neuromodulation. However, a majority of techniques avoid imaging during the active push transmit (interleaved or postpush acquisitions) to mitigate ultrasound interference, which leads to missing temporal information of ultrasound effects when FUS is being applied. Furthermore, critical for clinical translation, use of both axial steering and real-time (<1 s) capabilities for optimizing acoustic parameters for tissue engagement are largely missing. In this study, we describe a method of noninterleaved, single Vantage imaging displacement within an active FUS push with simultaneous axial steering and real-time capabilities using a single ultrasound acquisition machine. Results show that the pulse sequence can track micron-sized displacements using frame rates determined by the calculated time-of-flight (TOF), without interleaving the FUS pulses and imaging acquisition. Decimation by 3-7 frames increases signal-to-noise ratio (SNR) by 15.09±7.03 dB. Benchmarking tests of CUDA-optimized code show increase in processing speed of 35- and 300-fold in comparison with MATLAB parallel processing GPU and CPU functions, respectively, and we can estimate displacement from steered push beams ±10 mm from the geometric focus. Preliminary validation of displacement imaging in humans shows that the same driving pressures led to variable nerve engagement, demonstrating important feedback to improve transducer coupling, FUS incident angle, and targeting. Regarding the use of our technique for neuromodulation, we found that FUS altered thermal perception of thermal pain by 0.9643 units of pain ratings in a single trial. Additionally, 5 [Formula: see text] of nerve displacement was shown in on-target versus off-target sonications. The initial feasibility in healthy volunteers warrants further study for potential clinical translation of FUS for pain suppression.