Imaging Brain Fluids During Breathing

Neuroimaging the Impact of Respiration and Respiratory-gated Neuromodulation on Human Glymphatic Physiology

This study will perform magnetic resonance imaging (MRI) measurements of hemodynamics and cerebrospinal fluid flow across breathing tasks and during breath-locked neuromodulation.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Behavioral: Breathing task; Device: Transcutaneous vagal nerve stimulation

Detailed Description

Cerebrospinal fluid (CSF) flow is essential for brain health, as it clears waste products from the brain. This study will investigate how breathing affects the flow of CSF around the brain. The investigators will perform high resolution magnetic resonance imaging (MRI) scans in participants who are breathing in specific patterns or performing simple tasks and test the effects on CSF flow. Participants will complete an imaging study visit in which the investigators will image their brain activity while they perform simple tasks, including paced breathing tasks. The participants will be split into two arms: (1) paced breathing (25 participants low resolution, 15 participants high resolution), (2) transcutaneous vagal nerve stimulation (25 participants low resolution, 15 participants high resolution). The MRI scans will take place in the 7 Tesla MRI scanner at Massachusetts General Hospital.

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

Contacts and Locations

• Study Contact: Name: Jessica Yee, BS; Phone Number: 7742852038; Email: jessyee@bu.edu
• Study Contact Backup: Name: Courtney Zambello, BA; Phone Number: 7812019815; Email: cgz@bu.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Vitaly Napadow, MS, PhD; Phone Number: 617-732-9060; Email: vitaly@mgh.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Boston University - Charles River Campus
      • Contact: Jessica Yee, BS; Phone Number: 774-285-2038; Email: jessyee@bu.edu
      • Principal Investigator: Laura D Lewis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult age 18-70 years

Exclusion Criteria:

• No ferrous metal implanted in head or body
• No history of major head trauma
• No neurological or psychiatric disorder
• Not using medication that affects brain function
• No implanted electronic devices (e.g. pacemaker)
• No implant that poses an MR contraindication
• Not pregnant, suspect they are pregnant, or seeking to become pregnant
• Not claustrophobic
• No piercings or jewelry that cannot be removed
• Does not weigh more than 250 pounds
• Normal or contact-corrected normal vision

Exclusion for transcutaneous vagus nerve stimulation (tVNS) arm:

• Conditions of skin or anatomy that affect left auricle or forehead skin and could impact placement of electrodes for tVNS or forehead stimulation
• Diagnosis of significant cardiovascular or cerebrovascular disease [e.g. congestive heart failure, stroke, cardiac conduction disorders (including: bundle branch block, heart block, long Q-T syndrome), history of asystole or non-sustained ventricular tachycardia.
• Bradycardia (defined as resting heart rate <50 bpm)
• Hypotension defined as blood pressure <90/60 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Breath task; Participants will breathe in specific patterns.	Behavioral: Breathing task; Participants will be asked to breathe in specific patterns.
Experimental: Transcutaneous vagal nerve stimulation; Participants will receive transcutaneous vagal nerve stimulation in specific patterns.	Behavioral: Breathing task; Participants will be asked to breathe in specific patterns.; Device: Transcutaneous vagal nerve stimulation; Noninvasive stimulation vs sham stimulation will be delivered via an auricular device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
functional magnetic resonance imaging (fMRI) signals	fMRI measures of hemodynamic responses. Units: percent signal change	During study (2 hours)
Cerebrospinal fluid (CSF) signals	MR-based measures of CSF signals. Units: percent signal change	During study (2 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate variability will be calculated. Units: milliseconds (ms)	During study ( 2 hours)
Pulse oximetry	Amplitude of pulse oximetry signal. Units: arbitrary (no physical units are output by this system)	During study ( 2 hours)
Respiratory physiology timing	Breath timing. Units: Hertz (Hz)	During study (2 hours)
Respiratory physiology amplitude	Breath amplitude. Units: arbitrary (no physical units output by this sensor)	During study (2 hours)

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Laura Lewis, PhD, Boston University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Cerebrospinal fluid; Glymphatics
• Other Study ID Numbers: 6029E; R01AT011429 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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