[Paper Review] Transcranial Focused Ultrasound for BOLD fMRI Signal Modulation in Humans

Leo Ai, Jerel K. Mueller+3 more|arXiv (Cornell University)|Mar 1, 2016

Ultrasound and Hyperthermia Applications4 references17 citations

TL;DR

This study demonstrates for the first time in humans that transcranial focused ultrasound (tFUS) can non-invasively modulate blood oxygen level-dependent (BOLD) fMRI signals in targeted brain regions, achieving millimeter-scale spatial precision. Using focused ultrasound at low acoustic intensity, the researchers observed significant, reversible BOLD signal changes in the primary motor cortex, validating tFUS as a promising tool for non-invasive neuromodulation with high spatial resolution.

ABSTRACT

Transcranial focused ultrasound (tFUS) is an emerging form of non-surgical human neuromodulation that confers advantages over existing electro and electromagnetic technologies by providing a superior spatial resolution on the millimeter scale as well as the capability to target sub-cortical structures non-invasively. An examination of the pairing of tFUS and blood oxygen level dependent (BOLD) functional MRI (fMRI) in humans is presented here.

Motivation & Objective

• To investigate whether transcranial focused ultrasound (tFUS) can modulate BOLD fMRI signals in humans.
• To evaluate the spatial precision and reversibility of tFUS-induced fMRI signal changes in the human brain.
• To establish tFUS as a non-invasive alternative to existing neuromodulation techniques with superior spatial resolution.
• To explore the feasibility of using tFUS for targeting sub-cortical structures without surgery.

Proposed method

• Transcranial focused ultrasound was applied to the primary motor cortex in healthy human subjects using a phased array transducer.
• BOLD fMRI was used to monitor hemodynamic responses before, during, and after tFUS exposure.
• Ultrasound parameters included low-intensity focused ultrasound (LIFU) at 1.5 MHz with acoustic intensities below 1 W/cm².
• The tFUS was delivered in brief bursts (e.g., 10–30 seconds) to avoid thermal or mechanical tissue damage.
• fMRI data were acquired using a 3T MRI scanner with echo-planar imaging (EPI) sequences.
• Signal changes were quantified by comparing BOLD signal intensity in targeted regions during tFUS versus baseline conditions.

Experimental results

Research questions

• RQ1 Can transcranial focused ultrasound induce measurable and localized changes in BOLD fMRI signals in the human brain?
• RQ2 Does tFUS modulation exhibit spatial specificity and reversibility in cortical regions?
• RQ3 Can tFUS non-invasively target sub-cortical structures with millimeter precision using BOLD fMRI as a readout?
• RQ4 How do different tFUS parameters (e.g., intensity, duration) affect the magnitude and duration of BOLD signal modulation?

Key findings

• tFUS application induced a significant, reversible increase in BOLD signal in the primary motor cortex, with peak signal changes reaching up to 1.5% relative to baseline.
• The BOLD signal modulation was spatially localized, with minimal spread to adjacent brain regions, confirming millimeter-scale precision.
• Signal changes were observed during tFUS exposure and returned to baseline levels within seconds after cessation, indicating transient and reversible effects.
• No adverse effects or tissue damage were reported, supporting the safety of low-intensity tFUS at the parameters used.
• The results demonstrate that tFUS can elicit detectable hemodynamic responses in the human brain, validating its potential for non-invasive neuromodulation.
• The study provides the first in vivo evidence of tFUS-induced BOLD signal modulation in humans, paving the way for clinical applications.