Real time and delayed effects of subcortical low intensity focused ultrasound

Joshua A. Cain, Shakthi Visagan, Micah A. Johnson, Julia Crone, Robin Blades, Norman M. Spivak, David W. Shattuck, Martin M. Monti

Scientific Reports 2021, 11 · 10.1038/s41598-021-85504-y

human healthyhealthyfmriother mri

Abstract

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.

Abstract via europepmc.

Specieshuman

Subjects16 participants

Sessions per subject2

Randomisedyes

Blindingnot reported

Sham / controlnone

Auditory controlnot reported

Readout timingboth

Anaesthesianot applicable

Readoutsfmri, other mri — T2*-weighted BOLD fMRI during sonication; arterial spin labeling (ASL) perfusion MRI before/between/after sonication runs

Direction of effectinhibitoryMode 1 LIFU (100 Hz PRF, 0.5 ms pulse width) reduced BOLD signal in left GP and left thalamus during sonication and reduced whole-brain perfusion (ASL) afterward; Mode 2 (10 Hz PRF, 5 ms pulse width) produced no detectable BOLD effect despite the same intensity/duty cycle, but still reduced ASL perfusion.

Adverse eventsnot reported

Exposures

Exposure 1: Left globus pallidus LIFU, Mode 1 and Mode 2 parameter sets

Target: globus pallidus — “left globus pallidus (GP)”
Device: BrainSonix · Brainsonix Inc. · BXPulsar 1001 ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	650	✓✓✓
Pulse duration (ms)	0.5, 5swept	✓✓✓
Pulse repetition frequency (Hz)	100, 10swept	✓✓✓
Duty cycle (%)	5	✓✓✓
Sonication duration (s)	30	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported	⚑
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	deratingsingle value
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	14.4	✓✓✓⚑
In-situ Ispta (W/cm²)	0.72	✓✓✓

Protocol, in the paper’s words

Two 5-min LIFU runs per session, each consisting of ten 30-s sonication blocks preceded by 30-s rest blocks (block design). Each participant underwent two sessions on separate days (Mode 1 in one session, Mode 2 in the other, order counterbalanced), i.e. four 10-min sessions total, each containing 5 min of active sonication.

Flags from extraction

sham_type — No sham/inactive-transducer session; comparison is Mode1 vs Mode2 vs inter-block baseline rest, and right-hemisphere ROIs as anatomical control.
exposures[0].free_field.pressure_kpa — 1.0558 MPa is the pressure at the transducer face used as a simulation input parameter (water tank measurement), not necessarily the free-field focal pressure.
exposures[0].in_situ.isppa_w_cm2 — Isppa/Ispta values are labeled with a ".3" subscript denoting deration at 0.3 dB/cm-MHz through human tissue, i.e. an estimated in-situ (derated) value rather than a measured free-field value.