Low intensity focused ultrasound stimulation in stroke: A phase I safety & feasibility trial.

OBJECTIVE: We aimed to determine the maximum safe spatial-peak pulse-average intensity (ISPPA) 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 ISPPA (estimated in-vivo transcranial value) from 0, 1, 2, 4, 6, to 8 W/cm2. Stopping rules were pre-defined: 2nd-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-min 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: ISPPA 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 ISPPA is safe and feasible in stroke patients, and LIFUS at high intensity induces positive changes in 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.

Duke Scholars

Author Wuwei Feng Neurology, Stroke and Vascular Neurology

Author Sin-Ho Jung Biostatistics & Bioinformatics, Division of Integrative Geno ...

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Author Charalambos Costas Charalambous Neurology, Stroke and Vascular Neurology

Author Shashank Shekhar Neurology, Stroke and Vascular Neurology

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