Electrophysiological Source Imaging Guided Transcranial Focused Ultrasound

Neuromodulation is a fast growing field that offers a wide range of applications for both understanding and treating the brain. Future research for non-invasive neuromodulation will need to elucidate the optimal frequency, duration, and intensity of stimulation for a variety of technologies and diseases. Closed loop stimulation is thus a promising research area that allows for responsive stimulation and real time symptom management. Our project is proposed to develop and test a novel noninvasive neuromodulation integrating transcranial focused ultrasound stimulation (tFUS) with electrophysiological source imaging (ESI-tFUS) to allow evidence-based neuromodulation for brain research and the management of brain conditions. Despite the recent developments and attention surrounding tFUS, relatively little is known about the mechanisms and optimal parameters of this stimulation technology. The addition of ESI neuroimaging, aimed at providing biomarkers to assess the effects of tFUS neuromodulation, could provide crucial necessary information regarding the neural response to the applied stimulation in real-time. In order for tFUS to be further developed and transformed into a robust neuromodulation technology, an integrated electrophysiological source-imaging-guided tFUS system to allow for individualized and responsive stimulation is needed.

The purpose of this study is to develop and evaluate the proposed ESI-tFUS in human subjects using motor and somatosensory paradigms.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Device: Ultrasound

Detailed Description

In this protocol, the following hypothesis will be tested; the electroencephalography (EEG) and transcranial focused ultrasound (tFUS) will be used to quantify and optimize stimulation effects. We will test the hypothesis that tFUS can induce regional brain activity and use EEG to localize and image the brain electrical activity as induced by TFUS stimulation. Subjects will be recruited for MRI scan and then undergo motor and/or sensory tasks, and during these tasks, subjects will receive tFUS and concurrently be monitored by EEG. This tFUS-EEG study is aimed at exploring effects of tFUS and the use of EEG in providing electrophysiological responses to brain activation following tFUS stimulation.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kai Yu, Ph.D.; Phone Number: (612) 323-9748; Email: yukai@cmu.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Department of Biomedical Engineering, Carnegie Mellon University
      • Principal Investigator: Bin He, PhD
      • Contact: Kai Yu, Ph.D.; Email: yukai@cmu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Apparently healthy volunteers.
• Age 18-64.
• Willing and able to provide written consent.
• Able to communicate in the English language.

Exclusion Criteria:

Subjects having any of the following conditions will be excluded from this study:

• Evidence of a current significant medical illness or psychiatric or central or peripheral neurologic disorder
• History of loss of consciousness of more than ten minutes in the past year or loss of consciousness in a lifetime that required rehabilitation services
• Personal or family history of seizure
• Any history of stroke/transient ischemic attack (TIA)
• Taking any medications that are known to decrease the threshold for seizure
• Pregnancy
• Affirmative answers to one or more questions of the provided attached safety questionnaires. These are not absolute contraindications to this study but the risk/benefit ratio will be carefully considered by the PI
• Failure to follow laboratory or study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Real Ultrasound; The subjects will receive real ultrasound intervention.	Device: Ultrasound; Low-intensity (Ispta < 720 mW/cm2, Isppa < 190 W/cm2) transcranial focused ultrasound
Sham Comparator: Sham Ultrasound; The subjects will receive sham ultrasound intervention.	Device: Ultrasound; Low-intensity (Ispta < 720 mW/cm2, Isppa < 190 W/cm2) transcranial focused ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Closed-loop control of ultrasound neuromodulation as assessed by EEG source imaging	The primary study outcome is a closed-loop control algorithm to control the parameters in administrating the tFUS. The outcome data of the study will include the MRI data, EEG data, tFUS location and timing data, perceptual (subject reported) effects of tFUS and/or pins, and any reported adverse events. Analysis of the EEG data will be conducted using EEG analysis software, and the customized software to be developed at the PI's lab. The EEG data will also be correlated with tFUS application. The output of our data analysis process will be in the form of quantitative spatial estimation of tFUS activation in the brain using EEG source reconstruction.	up to 2 years

Collaborators and Investigators

• Sponsor: Carnegie Mellon University
• Investigators: Principal Investigator: Bin He, Ph.D., Carnegie Mellon University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 6, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: STUDY2017_00000426

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No