Lee Wonhye, Lee Stephanie D, Park Michael Y, Foley Lori, Purcell-Estabrook Erin, Kim Hyungmin, Fischer Krisztina, Maeng Lee-So, Yoo Seung-Schik
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Invasive Cardiovascular Experimental Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ultrasound Med Biol. 2016 Feb;42(2):459-70. doi: 10.1016/j.ultrasmedbio.2015.10.001. Epub 2015 Oct 30.
Non-invasive brain stimulation using focused ultrasound has largely been carried out in small animals. In the present study, we applied stimulatory focused ultrasound transcranially to the primary sensorimotor (SM1) and visual (V1) brain areas in sheep (Dorset, all female, n = 8), under the guidance of magnetic resonance imaging, and examined the electrophysiologic responses. By use of a 250-kHz focused ultrasound transducer, the area was sonicated in pulsed mode (tone-burst duration of 1 ms, duty cycle of 50%) for 300 ms. The acoustic intensity at the focal target was varied up to a spatial peak pulse-average intensity (Isppa) of 14.3 W/cm(2). Sonication of SM1 elicited electromyographic responses from the contralateral hind leg, whereas stimulation of V1 generated electroencephalographic potentials. These responses were detected only above a certain acoustic intensity, and the threshold intensity, as well as the degree of responses, varied among sheep. Post-sonication animal behavior was normal, but minor microhemorrhages were observed from the V1 areas exposed to highly repetitive sonication (every second for ≥500 times for electroencephalographic measurements, Isppa = 6.6-10.5 W/cm(2), mechanical index = 0.9-1.2). Our results suggest the potential translational utility of focused ultrasound as a new brain stimulation modality, yet also call for caution in the use of an excessive number of sonications.
使用聚焦超声的非侵入性脑刺激主要在小动物身上进行。在本研究中，我们在磁共振成像引导下，经颅向绵羊（多塞特羊，均为雌性，n = 8）的初级感觉运动（SM1）和视觉（V1）脑区应用刺激性聚焦超声，并检测电生理反应。使用250kHz聚焦超声换能器，以脉冲模式（音调猝发持续时间为1ms，占空比为50%）对该区域进行超声处理300ms。焦点目标处的声强变化至空间峰值脉冲平均强度（Isppa）为14.3W/cm²。对SM1进行超声处理可引起对侧后腿的肌电图反应，而刺激V1则产生脑电图电位。这些反应仅在一定声强以上才能检测到，阈值强度以及反应程度在绵羊之间有所不同。超声处理后动物行为正常，但在接受高度重复超声处理的V1区域（用于脑电图测量时每秒≥500次，Isppa = 6.6 - 10.5W/cm²，机械指数 = 0.9 - 1.2）观察到轻微的微出血。我们的结果表明聚焦超声作为一种新的脑刺激方式具有潜在的转化应用价值，但也提醒在使用过多超声处理时要谨慎。
