Low Intensity Focused Ultrasound Stimulation in Stroke: A Phase I Safety & Feasibility Trial.

Abstract

Objective: We aim to determine the maximum safe spatial-peak pulse-average intensity (I_SPPA) of low-intensity focused ultrasound stimulation (LIFUS) in stroke patients and explore its effect on motor learning and corticospinal excitability.

Methods: We adopted the classic 3+3 design to escalate I_SPPA (estimated in-vivo transcranial value) from 0, 1, 2, 4, 6, to 8 W/cm². Stopping rules were pre-defined: 2^nd-degree scalp burn, clinical seizure, new lesion on diffusion-weighted imaging or major reduction in apparent diffusion coefficient, and participant discontinuation due to any reason. We applied 12-minute LIFUS over the ipsilesional motor cortex while participants were concurrently practicing 3 blocks of a motor sequence learning (MSL) task using the affected hand. We measured MSL (response time) and corticospinal excitability (motor evoked potential) pre- and post-stimulation and compared MSL and corticospinal excitability between the LOW (0, 1, and 2 W/cm²) and HIGH (4, 6, and 8 W/cm²) groups.

Results: I_SPPA was escalated to 8 W/cm² with 18 stroke participants without meeting the stopping rules. Compared to the LOW, more participants in the HIGH performed better on MSL (6/9 vs. 0/9, p = 0.009) and showed a sign of greater corticospinal excitability (7/9 vs. 5/9, p = 0.62).

Interpretation: Our phase-I safety study suggests that one session of LIFUS up to 8 W/cm² I_SPPA is safe and feasible in stroke patients, and high intensity induces positive changes on both MSL and corticospinal excitability. The next logical step is to conduct a phase-II trial testing the efficacy of LIFUS and continuously monitoring its safety profiles.