Real time and delayed effects of subcortical low intensity focused ultrasound.
Authors: Cain JA, Visagan S, Johnson MA, Crone J, Blades R, Spivak NM, Shattuck DW, Monti MM
Deep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To determine whether non-invasive low-intensity focused ultrasound (LIFU) can modulate the left globus pallidus in healthy humans and to characterize the local and global (BOLD and perfusion) effects of two sonication modes.
Animal model / Human subject
Human (healthy volunteers); strain: N/A; age: 18–44 years (mean 25.25, SD 7.78); sex: 15 male (of 16 participants; 1 participant sex None)
Disease model
Healthy
MRI or image guidance method
MR image guidance: rapid T1-weighted scans with a circular MR fiducial on the transducer and visible transducer center; scanner-console reference lines drawn in transverse and coronal planes to visually position/iterate the transducer so the beam trajectory passes through the temporal bone into the anterodorsal left globus pallidus (with pre- and post-sonication rapid T1 scans for confirmation). CT/MRI-based acoustic simulations were also used for planning/validation.
Targeted brain region(s)
Globus Pallidus
Outcomes and Safety
Summary of Outcomes
Low‑intensity focused ultrasound (LIFU) targeting the left globus pallidus produced inhibitory effects: Mode 1 elicited immediate (online) decreases in BOLD signal locally (left GP) and in distal cortical networks, while both Mode 1 and Mode 2 produced longer‑lasting (offline) widespread decreases in cerebral perfusion (ASL); Mode 2 used a PRF of 10 Hz.
Duration of biological effect
30 s
Safety-related matter
No adverse events are reported; the study used low-intensity LIFU described as within intensities deemed safe for ultrasound imaging of the human cranium. The authors note potential concerns (at higher intensities) including vasoconstriction, MRI dropout, auditory/bone-conduction effects, skull-induced variability in energy deposition, and contrast LIFU with DBS risks such as hemorrhage and infection.
Brain Region
Ultrasound Parameters
Ultrasound instrument
BXPulsar 1001 (Brainsonix Inc.); transducer: 72 mm diameter single-element; focal depth 55 mm
FUS Frequency
650 kHz (carrier)
FUS Intensity
0.72 W/cm2; 14.40 W/cm2
FUS Pressure
1.0558 MPa
FUS Mode
pulsed
Pulse duration
0.5 ms (Mode 1) and 5 ms (Mode 2)
Duration of a single FUS session
10 minutes (10-min session; 5 min sonication ON time)
Focal Characteristics
Focal depth: 55 mm; Focal length: None; Aperture size: 72 mm
Treatment frequency
Multiple sessions
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