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Neuromodulation of sensory networks in monkey brain by focused ultrasound with MRI guidance and detection.

Authors: Yang PF, Phipps MA, Newton AT, Chaplin V, Gore JC, Caskey CF, Chen LM

Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions. The across-region differences in fMRI signal changes relative to area 3a/3b between tactile and FUS conditions also indicate that FUS modulated the tactile network differently. The significantly faster rising (>1 sec) fMRI signals elicited by direct FUS stimulation at the targeted cortical region suggest that a different neural hemodynamic coupling mechanism may be involved in generating fMRI signals. This is the first demonstration of imaging neural excitation effects of FUS with BOLD fMRI on a specific functional circuit in non-human primates.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To evaluate whether MRI-guided focused ultrasound can noninvasively and selectively excite specific somatosensory cortical targets and their associated circuits in non-human primates, as measured by 7 T BOLD fMRI.
Animal model / Human subject non-human primate, cynomolgus macaque, adult, male
Disease model healthy
MRI or image guidance method MRI-guided with fiducial-based registration and optical tracking: animals were placed in an MR stereotaxic frame with MRI-visible fiducial markers; prior tactile fMRI activation in areas 3a/3b was used to choose the target; the FUS transducer was optically tracked (NDI Polaris) and registered to the MRI via the fiducials; a laboratory-measured 3D free-field acoustic beam map (optically-tracked needle hydrophone) was projected into co-registered MRI voxels using 3D Slicer to overlay the estimated beam on the anatomical images.
Targeted brain region(s) S1

Outcomes and Safety

Summary of Outcomes 250 kHz FUS targeting S1 evoked local and circuit-wide BOLD activations with stronger hemodynamic responses than tactile stimuli.
Safety-related matter Negligible heating (<0.5°C) and no mechanical damage reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument H-115, Sonic Concepts
FUS Frequency 250 kHz
FUS Intensity 9.9 W/cm²
FUS Pressure 0.54 MPa
FUS Mode pulsed
Pulse duration 300 ms
Duration of a single FUS session 7.5 min
Focal Characteristics Not reported
Treatment frequency multiple sessions

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