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

IF 8.4 1区医学 Q1 CLINICAL NEUROLOGY Brain Stimulation Pub Date : 2025-01-01 DOI:10.1016/j.brs.2025.01.015

Ziping Huang , Charalambos C. Charalambous , Mengyue Chen , Taewon Kim , Estate Sokhadze , Allen Song , Sin-Ho Jung , Shashank Shekhar , Jody A. Feld , Xiaoning Jiang , Wuwei Feng

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Abstract

Objective

We aimed 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-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

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 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.

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低强度聚焦超声刺激治疗脑卒中：一期安全性和可行性试验。

目的：确定低强度聚焦超声刺激（LIFUS）对脑卒中患者的最大安全空间峰脉冲平均强度（ISPPA），并探讨其对运动学习和皮质脊髓兴奋性的影响。方法：我们采用经典的3+3设计，将ISPPA（估计体内经颅值）从0、1、2、4、6提高到8 W/cm2。停止规则是预先定义的：二度头皮烧伤、临床癫痫发作、弥散加权成像出现新病灶或表观弥散系数明显降低，以及参与者因任何原因停药。我们在同侧运动皮层上应用了12分钟的LIFUS，而参与者同时使用受影响的手练习3个运动序列学习（MSL）任务。我们测量了刺激前后的MSL（反应时间）和皮质脊髓兴奋性（运动诱发电位），并比较了低（0、1和2 W/cm2）组和高（4、6和8 W/cm2）组的MSL和皮质脊髓兴奋性。结果：18名中风患者在不符合停止规则的情况下，ISPPA升级到8 W/cm2。与LOW组相比，HIGH组中更多的参与者在MSL上表现更好（6/9 vs. 0/9, p = 0.009），并且表现出更大的皮质脊髓兴奋性（7/9 vs. 5/9, p = 0.62）。解释：我们的i期安全性研究表明，一次高达8w /cm2 ISPPA的LIFUS对脑卒中患者是安全可行的，高强度可诱导MSL和皮质脊髓兴奋性的积极变化。下一步是进行ii期试验，测试LIFUS的有效性，并持续监测其安全性。

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来源期刊

Brain Stimulation 医学-临床神经学

CiteScore

13.10

自引率

9.10%

发文量

256

审稿时长

72 days

期刊介绍： Brain Stimulation publishes on the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. Brain Stimulation aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) Original articles; b) Short Communications; c) Invited and original reviews; d) Technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) Letters to the Editor. Special issues of the journal will be considered based on scientific merit.