title: Image-Guided Focused Ultrasound-Mediated Regional Brain Stimulation in Sheep.
abstract: 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.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Wonhye
authors.initials: W
authors.lastname: Lee
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Park
authors.affiliation: Invasive Cardiovascular Experimental Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Foley
authors.affiliation: Invasive Cardiovascular Experimental Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Purcell-Estabrook
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Center for Bionics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Hyungmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
authors.forename: Lee-So
authors.initials: LS
authors.lastname: Maeng
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: yoo@bwh.harvard.edu.
authors.forename: Seung-Schik
authors.initials: SS
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000503:physiopathology* / Q000528:radiation effects*; D005071:Evoked Potentials / Q000502:physiology*; D019220:High-Energy Shock Waves; D008279:Magnetic Resonance Imaging / Q000379:methods*; D012756:Sheep; D014464:Ultrasonic Therapy / Q000379:methods*
keywords: Brain stimulation; Focused ultrasound; Large animal model; Sensorimotor area; Sheep; Visual area