Non-invasive measurement of hemodynamic change during 8 MHz transcranial focused ultrasound stimulation using near-infrared spectroscopy.

Transcranial focused ultrasound (tFUS) attracts wide attention in neuroscience as an effective noninvasive approach to modulate brain circuits. In spite of this, the effects of tFUS on the brain is still unclear, and further investigation is needed. The present study proposes to use near-infrared spectroscopy (NIRS) to observe cerebral hemodynamic change caused by tFUS in a noninvasive manner. The results show a transient increase of oxyhemoglobin and decrease of deoxyhemoglobin concentration in the mouse model induced by ultrasound stimulation of the somatosensory cortex with a frequency of 8 MHz but not in sham. In addition, the amplitude of hemodynamics change can be related to the peak intensity of the acoustic wave. High frequency 8 MHz ultrasound was shown to induce hemodynamic changes measured using NIRS through the intact mouse head. The implementation of NIRS offers the possibility of investigating brain response noninvasively for different tFUS parameters through cerebral hemodynamic change.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To determine whether near-infrared spectroscopy can noninvasively detect cerebral hemodynamic changes induced by transcranial focused ultrasound (8 MHz) in mice.

Animal model / Human subject Mouse (Mus musculus), BALB/c, 9–10 weeks old, female

Disease model healthy

MRI or image guidance method Stereotactic

Targeted brain region(s) Somatosensory Cortex

Target coordinates AP 0 mm, ML +1 mm, DV not specified; Detector fiber: AP -4 mm, ML +1 mm, DV not specified

Route of administration Intraperitoneal injection

Outcomes and Safety

Summary of Outcomes In mice, 8 MHz transcranial focused ultrasound (5 s: 10 pulse trains, 300 pulses of 500 cycles, PRF 1500 Hz) caused transient increases in oxyhemoglobin and decreases in deoxyhemoglobin measured by NIRS (no visible motor response), with larger hemodynamic responses at higher acoustic intensities (tested I_SPTA ≈ 468 and 1077 mW/cm^2 — after skull attenuation ≈129 and 56 mW/cm^2).

Duration of biological effect 5 s

Safety-related matter The authors report the applied ultrasound had a mechanical index of 0.2 (well below the clinical limit of 1.9) and in-skull intensities of 129 and 56 mW/cm2 (below the imaging guideline of 720 mW/cm2), with an estimated brain temperature rise <0.01°C and no obvious post-stimulation behavioral abnormalities; prior studies using much higher acoustic energy also did not show tissue damage, minimizing the likelihood of cavitation- or heat-related brain injury.

Brain Region

Ultrasound Parameters

Ultrasound instrument function generator (Agilent 33220A, Keysight, USA) amplified at (E&I 240L, USA)

FUS Frequency 8 MHz; 1.5 kHz

FUS Intensity 1.077 W/cm2 and 0.468 W/cm2

FUS Pressure Not provided

FUS Mode pulsed

Pulse duration 5 s

Duration of a single FUS session 17 s

Focal Characteristics 1.76 mm

Treatment frequency single

We are open to feedback. If you see a mistake or have a suggestion, please contact us.